Integrating in silico and in vitro analysis of peptide binding affinity to HLA-Cw*0102:a bioinformatic approach to the prediction of new epitopes

Predictive models of peptide-Major Histocompatibility Complex (MHC) binding affinity are important components of modern computational immunovaccinology. Here, we describe the development and deployment of a reliable peptide-binding prediction method for a previously poorly-characterized human MHC class I allele, HLA-Cw*0102.

A process framework for selecting supply system architecture in manufacturing supply chains and networks

The process framework comprises three phases, as follows: scope the supply chain/network; identify the options for supply system architecture and select supply system architecture. It facilitates a structured approach that analyses the supply chain/network contextual characteristics, in order to ensure alignment with the appropriate supply system architecture. The process framework was derived from comprehensive literature review and archival case study analysis. The review led to the classification of supply system architectures according to their orientation, whether integrated; partially integrated; co-ordinated or independent. The classification was combined with the characteristics that influence the selection of supply system architecture to encapsulate the conceptual framework. It builds upon existing frameworks and methodologies by focusing on structured procedure; supporting project management; facilitating participation and clarifying point of entry. The process framework was initially tested in three case study applications from the food, automobile and hand tool industries. A variety of industrial settings was chosen to illustrate transferability. The case study applications indicate that the process framework is a valid approach to the problem; however, further testing is required. In particular, the use of group support system technologies to support the process and the steps involving the participation of software vendors need further testing. However, the process framework can be followed due to the clarity of its presentation. It considers the issue of timing by including alternative decision-making techniques, dependent on the constraints. It is useful for ensuring a sound business case is developed, with supporting documentation and analysis that identifies the strategic and functional requirements of supply system architecture.

Strategic positioning of manufacturing operations within global supply chains

In global environment, a company has to make many decisions that impact upon its position in global supply chain networks such as outsourcing, offshoring, joint venture, vertical/horizontal integration, etc. All these decisions impact on the company’s strategic position, and hence on competitive space and performance. Therefore, it is important for a company to carefully manage strategic positioning by making careful decisions about the adoption of alternative manufacturing and supply chain activities. Unfortunately, there is no complete process studied in strategic positioning of manufacturing operations within global supply chain. Therefore, the work presented in this paper has investigated leading research and industrial practices to create a formal and rational decision process. An analysis of previous literature, industrial practices, and the resulting decision process are all presented in this paper.

Success factors in a forming strategic positioning of manufacturing operations within global supply chains

Managing supply chains effectively has become a critical element in enhancing company profitability and has been identified as the new frontier of competitive advantage. An important element of effective supply chain management is the strategic positioning of the company. The strategic positioning process is concerned with the choice of production-centred activities a company carries out internally and those provided externally. Strategic positioning within manufacturing supply chains however is a relatively recent research topic with apparently few articles currently available that explicitly address associated issues directly. Moreover there is no previous research working strategic positioning of manufacturing operations in global context. Therefore the purpose of this paper is to explore strategic positioning within global supply chains. This paper is based on three cases drawn from the cross industry sector manufacturing companies. It describes an exploratory analysis which is aimed at gaining insight into the success factor to form a strategic positioning within global supply chains.

Strategic positioning of manufacturing operations within global supply chains

This paper describes research that has sought to create a structured and integrated methodology that guides manufacturers through the decision of strategic positioning within global supply chains. The position of a company is concerned with deciding a boundary and configuration of internal and external business activities to the company and is directly related to initiatives such as outsourcing, make or buy, and offshoring. This paper provides an in-depth description of this concept, describes work carried out to form a methodology for strategic positioning within the global supply chain, and presents the details of the methodology. This research has made a significant contribution to the knowledge on how manufacturing companies can form a strategic positioning within global supply chains.

Identification of the HLA-DM/HLA-DR interface

Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the dissociation of the Class II-associated Invariant chain-derived Peptide (CLIP) from the major histocompatibility complex (MHC) Class II molecules. There is competition amongst peptides for access to an MHC Class II groove and it has been hypothesised that DM functions as a 'peptide editor' that catalyzes the replacement of one peptide for another within the groove. It is established that the DM catalyst interacts directly with the MHC Class II but the precise location of the interface is unknown. Here, we combine previously described mutational data with molecular docking and energy minimisation simulations to identify a putative interaction site of >4000A2 which agrees with known point mutational data for both the DR and DM molecule. The docked structure is validated by comparison with experimental data and previously determined properties of protein-protein interfaces. A possible dissociation mechanism is suggested by the presence of an acidic cluster near the N terminus of the bound peptide.

Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly

The molecular chaperone, Hsc70, together with its cofactor, auxilin, facilitates the ATP-dependent removal of clathrin during clathrin-mediated endocytosis in cells. We have used cryo-electron microscopy to determine the 3D structure of a complex of clathrin, auxilin401-910 and Hsc70 at pH 6 in the presence of ATP, frozen within 20 seconds of adding Hsc70 in order to visualize events that follow the binding of Hsc70 to clathrin and auxilin before clathrin disassembly. In this map,we observe density beneath the vertex of the cage that we attribute to bound Hsc70. This density emerges asymmetrically from the clathrin vertex, suggesting preferential binding by Hsc70 for one of the three possible sites at the vertex. Statistical comparison with a map of whole auxilin and clathrin previously published by us reveals the location of statistically significant differences which implicate involvement of clathrin light chains in structural rearrangements which occur after Hsc70 is recruited. Clathrin disassembly assays using light scattering suggest that loss of clathrin light chains reduces the efficiency with which auxilin facilitates this reaction. These data support a regulatory role for clathrin light chains in clathrin disassembly in addition to their established role in regulating clathrin assembly. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Linked data for the 21st Century enterprise:from silos to supply chains

Six actions for collation collective intelligence to inform and accelerate change

Building up resilience of construction sector SMEs and their supply chains to extreme weather events

Wider scientific community now accept that the threat of climate change as real and thus acknowledge the importance of implementing adaptation measures in a global context. In the UK , the physical effects of climate change are likely to be directly felt in the form of extreme weather events, which are predicted to escalate in number and severity in future under the changing climatic conditions. Construction industry; which consists of supply chains running across various other industries, economies and regions, will also be affected due to these events. Thus, it is important that the construction organisations are well prepared to withstand the effects of extreme weather events not only directly affecting their organisations but also affecting their supply chains which in turn might affect the organisation concerned. Given the fact that more than 99% of construction sector businesses are SMEs, the area can benefit significantly from policy making to improve SME resilience and coping capacity. This paper presents the literature review and synthesis of a doctoral research study undertaken to address the issue of extreme weather resilience of construction sector SMEs and their supply chains. The main contribution of the paper to both academia and practitioners is a synthesis model that conceptualises the factors that enhances resilience of SMEs and their supply chains against extreme weather events. This synthesis model forms the basis of a decision making framework that will enable SMEs to both reduce their vulnerability and enhance their coping capacity against extreme weather. The value of this paper is further extended by the overall research design that is set forth as the way forward.

Reverse resource exchanges in service supply chains:the case of returnable transport packaging

Purpose: The purpose of this paper is to understand how reverse resource exchanges and resource dependencies are managed in the service supply chain (SSC) of returnable transport packaging (RTP). Design/methodology/approach: A single case study was conducted in the context of automotive logistics focusing on the RTP SSC. Data were collected through 16 interviews, primarily with managers of a logistics service provider (LSP) and document analysis of contractual agreements with key customers of the packaging service. Findings: Resource dependencies among actors in the SSC result from the importance of the RTP for the customer’s production processes, the competition among users for RTP and the negative implications of the temporary unavailability of RTP for customers and the LSP (in terms of service performance). Amongst other things, the LSP is dependent on its customers and third-party users (e.g. the customer’s suppliers) for the timely return of package resources. The role of inter-firm integration and collaboration, formal contracts as well as customers’ power and influence over third-party RTP users are stressed as key mechanisms for managing LSP’s resource dependencies. Research limitations/implications: A resource dependence theory (RDT) lens is used to analyse how reverse resource exchanges and associated resource dependencies in SSCs are managed, thus complementing the existing SSC literature emphasising the bi-directionality of resource flows. The study also extends the recent SSC literature stressing the role of contracting by empirically demonstrating how formal contracts can be mobilised to explicate resource dependencies and to specify, and regulate, reverse exchanges in the SSC. Practical implications: The research suggests that logistics providers can effectively manage their resource dependencies and regulate reverse exchanges in the SSC by deploying contractual governance mechanisms and leveraging their customers’ influence over third-party RTP users. Originality/value: The study is novel in its application of RDT, which enhances our understanding of the management of reverse exchanges and resource dependencies in SSCs.

The relationship between high-sensitivity CRP and polyclonal Free Light Chains as markers of inflammation in chronic disease

Introduction: Serum concentrations of polyclonal free light chains (FLC) represent the activity of the adaptive immune system. This study assessed the relationship between polyclonal FLC and the established marker of innate immunity, C-reactive protein (CRP), in chronic and acute disease. Methods: We utilized four cross-sectional chronic disease patient cohorts: chronic kidney disease (CKD), diabetes, vasculitis and kidney transplantation; and a longitudinal intensive care case series to assess the kinetics of production in acute disease. Results: There was a weak association between polyclonal FLC and high-sensitivity CRP (hs-CRP) in the study cohorts. A longitudinal assessment in acute disease showed a gradual increase in FLC concentrations over time, often when CRP levels were falling, demonstrating clear differences in the response kinetics of CRP and FLC in this setting. Conclusion: Polyclonal FLC and hs-CRP provide independent information as to inflammatory status. Prospective studies are now required to assess the utility of hs-CRP and polyclonal FLC in combination for risk stratification in disease populations. © 2013 John Wiley & Sons Ltd.

Designing post-disaster supply chains:learning from housing reconstruction projects

Post-disaster housing reconstruction projects face several challenges. Resources and material supplies are often scarce; several and different types of organizations are involved, while projects must be completed as quickly as possible to foster recovery. Within this context, the chapter aims to increase the understanding of relief supply chain design in reconstruction. In addition, the chapter is introducing a community based and beneficiary perspective to relief supply chains by evaluating the implications of local components for supply chain design in reconstruction. This is achieved through the means of secondary data analysis based on the evaluation reports of two major housing reconstruction projects that took place in Europe the last decade. A comparative analysis of the organizational designs of these projects highlights the ways in which users can be involved. The performance of reconstruction supply chains seems to depend to a large extent on the way beneficiaries are integrated in supply chain design impacting positively on the effectiveness of reconstruction supply chains.