914 resultados para HLA-DRB1 Chains


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Purpose - To develop a systems strategy for supply chain management in aerospace maintenance, repair and overhaul (MRO). Design/methodology/approach - A standard systems development methodology has been followed to produce a process model (i.e. the AMSCR model); an information model (i.e. business rules) and a computerised information management capability (i.e. automated optimisation). Findings - The proof of concept for this web-based MRO supply chain system has been established through collaboration with a sample of the different types of supply chain members. The proven benefits comprise new potential to minimise the stock holding costs of the whole supply chain whilst also minimising non-flying time of the aircraft that the supply chain supports. Research limitations/implications - The scale of change needed to successfully model and automate the supply chain is vast. This research is a limited-scale experiment intended to show the power of process analysis and automation, coupled with strategic use of management science techniques, to derive tangible business benefit. Practical implications - This type of system is now vital in an industry that has continuously decreasing profit margins; which in turn means pressure to reduce servicing times and increase the mean time between them. Originality/value - Original work has been conducted at several levels: process, information and automation. The proof-of-concept system has been applied to an aircraft MRO supply chain. This is an area of research that has been neglected, and as a result is not well served by current systems solutions. © Emerald Group Publishing Limited.

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The topic of bioenergy, biofuels and bioproducts remains at the top of the current political and research agenda. Identification of the optimum processing routes for biomass, in terms of efficiency, cost, environment and socio-economics is vital as concern grows over the remaining fossil fuel resources, climate change and energy security. It is known that the only renewable way of producing conventional hydrocarbon fuels and organic chemicals is from biomass, but the problem remains of identifying the best product mix and the most efficient way of processing biomass to products. The aim is to move Europe towards a biobased economy and it is widely accepted that biorefineries are key to this development. A methodology was required for the generation and evaluation of biorefinery process chains for converting biomass into one or more valuable products that properly considers performance, cost, environment, socio-economics and other factors that influence the commercial viability of a process. In this thesis a methodology to achieve this objective is described. The completed methodology includes process chain generation, process modelling and subsequent analysis and comparison of results in order to evaluate alternative process routes. A modular structure was chosen to allow greater flexibility and allowing the user to generate a large number of different biorefinery configurations The significance of the approach is that the methodology is defined and is thus rigorous and consistent and may be readily re-examined if circumstances change. There was the requirement for consistency in structure and use, particularly for multiple analyses. It was important that analyses could be quickly and easily carried out to consider, for example, different scales, configurations and product portfolios and so that previous outcomes could be readily reconsidered. The result of the completed methodology is the identification of the most promising biorefinery chains from those considered as part of the European Biosynergy Project.

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Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells. MHC proteins are divided into Class I and Class II. Human MHC Class II alleles are grouped into three loci: HLA-DP, HLA-DQ, and HLA-DR. They are involved in many autoimmune diseases. In contrast to HLA-DR and HLA-DQ proteins, the X-ray structure of the HLA-DP2 protein has been solved quite recently. In this study, we have used structure-based molecular dynamics simulation to derive a tool for rapid and accurate virtual screening for the prediction of HLA-DP2-peptide binding. A combinatorial library of 247 peptides was built using the "single amino acid substitution" approach and docked into the HLA-DP2 binding site. The complexes were simulated for 1 ns and the short range interaction energies (Lennard-Jones and Coulumb) were used as binding scores after normalization. The normalized values were collected into quantitative matrices (QMs) and their predictive abilities were validated on a large external test set. The validation shows that the best performing QM consisted of Lennard-Jones energies normalized over all positions for anchor residues only plus cross terms between anchor-residues.

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E-business adoption rates in the agri-food sector are rather low, despite the fact that technical barriers have been mostly overcome during the last years and a large number of sophisticated offers are available. However, concerns about trust seem to impede the development of electronic relationships in the agri-food chains as trust is of particular importance in any exchange of agri-food products along the value chain. Drawing on existing research, characteristics and dimensions of trust are initially identified both in traditional and in electronic B2B relationships and a typology of trust is proposed. The aim of the paper is to provide an overview of the implementation and use of trust elements that e-commerce offers dedicated to agri-food sector. This assessment will show the current situation and discuss gaps for further improvement with the objective to facilitate the uptake of e-commerce in agri-food chains. © 2009 Elsevier B.V. All rights reserved.

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MHC class II proteins bind oligopeptide fragments derived from proteolysis of pathogen antigens, presenting them at the cell surface for recognition by CD4+ T cells. Human MHC class II alleles are grouped into three loci: HLA-DP, HLA-DQ and HLA-DR. In contrast to HLA-DR and HLA-DQ, HLA-DP proteins have not been studied extensively, as they have been viewed as less important in immune responses than DRs and DQs. However, it is now known that HLA-DP alleles are associated with many autoimmune diseases. Quite recently, the X-ray structure of the HLA-DP2 molecule (DPA*0103, DPB1*0201) in complex with a self-peptide derived from the HLA-DR a-chain has been determined. In the present study, we applied a validated molecular docking protocol to a library of 247 modelled peptide-DP2 complexes, seeking to assess the contribution made by each of the 20 naturally occurred amino acids at each of the nine binding core peptide positions and the four flanking residues (two on both sides).

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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.

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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.

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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.

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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.

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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.

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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.

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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.