Enhanced integrated modelling approach to reconfiguring manufacturing enterprises

Dynamism and uncertainty are real challenges for present day manufacturing enterprises (MEs). Reasons include: an increasing demand for customisation, reduced time to market, shortened product life cycles and globalisation. MEs can reduce competitive pressure by becoming reconfigurable and change-capable. However, modern manufacturing philosophies, including agile and lean, must complement the application of reconfigurable manufacturing paradigms. Choosing and applying the best philosophies and techniques is very difficult as most MEs deploy complex and unique configurations of processes and resource systems, and seek economies of scope and scale in respect of changing and distinctive product flows. It follows that systematic methods of achieving model driven reconfiguration and interoperation of component based manufacturing systems are required to design, engineer and change future MEs. This thesis, titled Enhanced Integrated Modelling Approach to Reconfiguring Manufacturing Enterprises , introduces the development and prototyping a model-driven environment for the design, engineering, optimisation and control of the reconfiguration of MEs with an embedded capability to handle various types of change. The thesis describes a novel systematic approach, namely enhanced integrated modelling approach (EIMA), in which coherent sets of integrated models are created that facilitates the engineering of MEs especially their production planning and control (PPC) systems. The developed environment supports the engineering of common types of strategic, tactical and operational processes found in many MEs. The EIMA is centred on the ISO standardised CIMOSA process modelling approach. Early study led to the development of simulation models during which various CIMOSA shortcomings were observed, especially in its support for aspects of ME dynamism. A need was raised to structure and create semantically enriched models hence forming an enhanced integrated modelling environment. The thesis also presents three industrial case examples: (1) Ford Motor Company; (2) Bradgate Furniture Manufacturing Company; and (3) ACM Bearings Company. In order to understand the system prior to realisation of any PPC strategy, multiple process segments of any target organisation need to be modelled. Coherent multi-perspective case study models are presented that have facilitated process reengineering and associated resource system configuration. Such models have a capability to enable PPC decision making processes in support of the reconfiguration of MEs. During these case studies, capabilities of a number of software tools were exploited such as Arena®, Simul8®, Plant Simulation®, MS Visio®, and MS Excel®. Case study results demonstrated effectiveness of the concepts related to the EIMA. The research has resulted in new contributions to knowledge in terms of new understandings, concepts and methods in following ways: (1) a structured model driven integrated approach to the design, optimisation and control of future reconfiguration of MEs. The EIMA is an enriched and generic process modelling approach with capability to represent both static and dynamic aspects of an ME; and (2) example application cases showing benefits in terms of reduction in lead time, cost and resource load and in terms of improved responsiveness of processes and resource systems with a special focus on PPC; (3) identification and industrial application of a new key performance indicator (KPI) known as P3C the measuring and monitoring of which can aid in enhancing reconfigurability and responsiveness of MEs; and (4) an enriched modelling concept framework (E-MUNE) to capture requirements of static and dynamic aspects of MEs where the conceptual framework has the capability to be extended and modified according to the requirements. The thesis outlines key areas outlining a need for future research into integrated modelling approaches, interoperation and updating mechanisms of partial models in support of the reconfiguration of MEs.

Design and formulation of functional pluripotent stem cell-derived cardiac microtissues.

Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function.

Changes in biomechanical properties of the coronary artery wall contribute to maintained contractile responses to endothelin-1 in atherosclerosis.

AIMS: Our aim was to determine whether alterations in biomechanical properties of human diseased compared to normal coronary artery contribute to changes in artery responsiveness to endothelin-1 in atherosclerosis. MAIN METHODS: Concentration-response curves were constructed to endothelin-1 in normal and diseased coronary artery. The passive mechanical properties of arteries were determined using tensile ring tests from which finite element models of passive mechanical properties of both groups were created. Finite element modelling of artery endothelin-1 responses was then performed. KEY FINDINGS: Maximum responses to endothelin-1 were significantly attenuated in diseased (27±3 mN, n=55) compared to normal (38±2 mN, n=68) artery, although this remained over 70% of control. There was no difference in potency (pD2 control=8.03±0.06; pD2 diseased=7.98±0.06). Finite element modelling of tensile ring tests resulted in hyperelastic shear modulus μ=2004±410 Pa and hardening exponent α=22.8±2.2 for normal wall and μ=2464±1075 Pa and α=38.3±6.7 for plaque tissue and distensibility of diseased vessels was decreased. Finite element modelling of active properties of both groups resulted in higher muscle contractile strain (represented by thermal reactivity) of the atherosclerotic artery model than the normal artery model. The models suggest that a change in muscle response to endothelin-1 occurs in atherosclerotic artery to increase its distensibility towards that seen in normal artery. SIGNIFICANCE: Our data suggest that an adaptation occurs in medial smooth muscle of atherosclerotic coronary artery to maintain distensibility of the vessel wall in the presence of endothelin-1. This may contribute to the vasospastic effect of locally increased endothelin-1 production that is reported in this condition.