963 resultados para Process Re-engineering
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Background Canonical serine protease inhibitors commonly bind to their targets through a rigid loop stabilised by an internal hydrogen bond network and disulfide bond(s). The smallest of these is sunflower trypsin inhibitor (SFTI-1), a potent and broad-range protease inhibitor. Recently, we re-engineered the contact β-sheet of SFTI-1 to produce a selective inhibitor of kallikrein-related peptidase 4 (KLK4), a protease associated with prostate cancer progression. However, modifications in the binding loop to achieve specificity may compromise structural rigidity and prevent re-engineered inhibitors from reaching optimal binding affinity. Methodology/Principal Findings In this study, the effect of amino acid substitutions on the internal hydrogen bonding network of SFTI were investigated using an in silico screen of inhibitor variants in complex with KLK4 or trypsin. Substitutions favouring internal hydrogen bond formation directly correlated with increased potency of inhibition in vitro. This produced a second generation inhibitor (SFTI-FCQR Asn14) which displayed both a 125-fold increased capacity to inhibit KLK4 (Ki = 0.0386±0.0060 nM) and enhanced selectivity over off-target serine proteases. Further, SFTI-FCQR Asn14 was stable in cell culture and bioavailable in mice when administered by intraperitoneal perfusion. Conclusion/Significance These findings highlight the importance of conserving structural rigidity of the binding loop in addition to optimising protease/inhibitor contacts when re-engineering canonical serine protease inhibitors.
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Objective: To describe the reported impact of Pandemic (H1N1) 2009 on EDs, so as to inform future pandemic policy, planning and response management. Methods: This study comprised an issue and theme analysis of publicly accessible literature, data from jurisdictional health departments, and data obtained from two electronic surveys of ED directors and ED staff. The issues identified formed the basis of policy analysis and evaluation. Results: Pandemic (H1N1) 2009 had a significant impact on EDs with presentation for patients with ‘influenza-like illness’ up to three times that of the same time in previous years. Staff reported a range of issues, including poor awareness of pandemic plans, patient and family aggression, chaotic information flow to themselves and the public, heightened stress related to increased workloads and lower levels of staffing due to illness, family care duties and redeployment of staff to flu clinics. Staff identified considerable discomfort associated with prolonged times wearing personal protective equipment. Staff believed that the care of non-flu patients was compromised during the pandemic as a result of overwork, distraction from core business and the difficulties associated with accommodating infectious patients in an environment that was not conducive. Conclusions: This paper describes the breadth of the impact of pandemics on ED operations. It identifies a need to address a range of industrial, management and procedural issues. In particular, there is a need for a single authoritative source of information, the re-engineering of EDs to accommodate infectious patients and organizational changes to enable rapid deployment of alternative sources of care.
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Designed for undergraduate and postgraduate students, academic researchers and industrial practitioners, this book provides comprehensive case studies on numerical computing of industrial processes and step-by-step procedures for conducting industrial computing. It assumes minimal knowledge in numerical computing and computer programming, making it easy to read, understand and follow. Topics discussed include fundamentals of industrial computing, finite difference methods, the Wavelet-Collocation Method, the Wavelet-Galerkin Method, High Resolution Methods, and comparative studies of various methods. These are discussed using examples of carefully selected models from real processes of industrial significance. The step-by-step procedures in all these case studies can be easily applied to other industrial processes without a need for major changes and thus provide readers with useful frameworks for the applications of engineering computing in fundamental research problems and practical development scenarios.
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An experimental study of the properties of hydrodynamic forces upon a marine pipeline is presented in this paper, in the equilibrium scour conditions for various Keulegan-Carpenter numbers and various initial relative gaps between pipeline and the erosive sandy seabed. The tests are conducted in a U-shaped oscillatory water tunnel with a sand box located at the bottom of the test section. According to the experimental results, the maximum horizontal forces on the pipelines with an initial gap to seabed will decrease to some extent due to scouring process. For engineering appliances, it seems safer to estimate wave induced forces on pipelines under the assumption that seabed is plane. However, it should be noticed that great changes would be brought to the frequency properties of lift forces because of the sandy scour beneath the pipeline, which occurs for certain KC numbers.
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This paper describes a method for monitoring the variation in support condition of pipelines using a vibration technique. The method is useful for detecting poor support of buried pipelines and for detecting spanning and depth of cover in sub-sea lines. Variation in the pipe support condition leads to increased likelihood of pipe damage. Under roadways, poorly supported pipe may be damaged by vehicle loading. At sea, spanned sections of pipe are vulnerable to ocean current loading and also to snagging by stray anchors in shallow waters. A vibrating `pig' has been developed and tested on buried pipelines. Certain features of pipe support, such as voids and hard spots, display characteristic responses to vibration, and these are measured by the vibrating pig. Post-processing of the measured vibration data is used to produce a graphical representation of the pipeline support and certain `feature characteristics' are identified. In field tests on a pipeline with deliberately constructed support faults, features detected by the vibrating pig are in good agreement with the known construction.
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Current research into the process of engineering design is extending the use of computers towards the acquisition, representation and application of design process knowledge in addition to the existing storage and manipulation of product-based models of design objects. This is a difficult task because the design of mechanical systems is a complex, often unpredictable process involving ill-structured problem solving skills and large amounts of knowledge, some which may be of an incomplete and subjective nature. Design problems require the integration of a variety of modes of working such as numerical, graphical, algorithmic or heuristic and demand products through synthesis, analysis and evaluation activities.
This report presents the results of a feasibility study into the blackboard approach and discusses the development of an initial prototype system that will enable an alphanumeric design dialogue between a designer and an expert to be analysed in a formal way, thus providing real-life protocol data on which to base the blackboard message structures.
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为了满足用户对软件系统内部业务过程定义的定制需求,针对流行的J2EE平台,以工作流技术为基础设计了对遗留软件系统的改造平台JSPMP。JSPMP利用工作流引擎的过程定义与任务管理能力驱动系统业务流程执行,赋予软件系统在业务过程定义方面的动态可定制性。实践证明,开发者利用此方案能够迅速改造遗留系统,满足用户多样化的过程定制需求,极大地降低了改造、定制成本。
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The demands of the process of engineering design, particularly for structural integrity, have exploited computational modelling techniques and software tools for decades. Frequently, the shape of structural components or assemblies is determined to optimise the flow distribution or heat transfer characteristics, and to ensure that the structural performance in service is adequate. From the perspective of computational modelling these activities are typically separated into: • fluid flow and the associated heat transfer analysis (possibly with chemical reactions), based upon Computational Fluid Dynamics (CFD) technology • structural analysis again possibly with heat transfer, based upon finite element analysis (FEA) techniques.
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A new approach to the prediction of bend lifetime in pneumatic conveyors, subject to erosive wear is described. Mathematical modelling is exploited. Commercial Computational Fluid Dynamics (CFD) software is used for the prediction of air flow and particle tracks, and custom code for the modelling of bend erosion and lifetime prediction. The custom code uses a toroidal geometry, and employs a range of empirical data rather than trying to fit classical erosion models to a particular circumstance. The data used was obtained relatively quickly and easily from a gas-blast erosion tester. A full-scale pneumatic conveying rig was used to validate a sample of the bend lifetime predictions, and the results suggest accuracy of within ±65%, using calibration methods. Finally, the work is distilled into user-friendly interactive software that will make erosion lifetime predictions for a wide range of bends under varying conveying conditions. This could be a valuable tool for the pneumatic conveyor design or maintenance engineer.
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Problems in the preservation of the quality of granular material products are complex and arise from a series of sources during transport and storage. In either designing a new plant or, more likely, analysing problems that give rise to product quality degradation in existing operations, practical measurement and simulation tools and technologies are required to support the process engineer. These technologies are required to help in both identifying the source of such problems and then designing them out. As part of a major research programme on quality in particulate manufacturing computational models have been developed for segregation in silos, degradation in pneumatic conveyors, and the development of caking during storage, which use where possible, micro-mechanical relationships to characterize the behaviour of granular materials. The objective of the work presented here is to demonstrate the use of these computational models of unit processes involved in the analysis of large-scale processes involving the handling of granular materials. This paper presents a set of simulations of a complete large-scale granular materials handling operation, involving the discharge of the materials from a silo, its transport through a dilute-phase pneumatic conveyor, and the material storage in a big bag under varying environmental temperature and humidity conditions. Conclusions are drawn on the capability of the computational models to represent key granular processes, including particle size segregation, degradation, and moisture migration caking.
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In this paper the dependence of the power consumption of pneumatic conveyors upon conveyed materials, pipeline route and bore, and mode of flow has been examined. The findings are that, with different materials and modes of flow, not only is the amount of power consumed very different but it varies in different ways with pipe bore and routing. Additionally it has been found that, for any given conveying system, the choice of air mover also has a strong influence on the power requirement.
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The prediction of the pressure drop for turbulent single-phase fluid flow around sharp 90° bends is difficult owing to the complexity of the flow arising from frictional and separation effects. Several empirical equations exist, which accurately predict the pressure loss due to frictional effects. More recently, Crawford et al. [1] proposed an equation for the prediction of pressure loss due to separation of the flow. This work proposes a new composite equation for the prediction of pressure drop due to separation of the flow, which incorporates bends with ratio R/r <2. A new composite equation is proposed to predict pressure losses over the Reynolds number range 4 x 103-3 x 105. The predictions from the new equation are within a range of -4 to +6 per cent of existing experimental data.
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Computational fluid dynamic modelling was carried out on a series of pipe bends having R/r values of 1.3, 5, and 20, with the purpose of determining the accuracy of numerical models in predicting pressure loss data from which to inform one-dimensional loss models. Four separate turbulence models were studied: the standard k-epsilon model, realizable k-epsilon model, k-omega model, and a Reynolds stress model (RSM). The results are presented for each bend in the form of upstream and downstream pressure profiles, pressure distributions along the inner and outer walls, detailed pressure and velocity fields as well as overall loss values. In each case, measured data were presented to evaluate the predictive ability of each model. The RSM was found to perform the best, producing accurate pressure loss data for bends with R/r values of 5 and 20. For the tightest bend with an R/r value of 1.3, however, predictions were significantly worse due to the presence of flow separation, stronger pressure gradients, and high streamline curvature.