874 research outputs found

    Simulating intertwined design processes that have similar structures: A case study of a small company that creates made-to-order fashion products

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    The authors use simulation to analyse the resource-driven dependencies between concurrent processes used to create customised products in a company. Such processes are uncertain and unique according to the design changes required. However, they have similar structures. For simulation, a level of abstraction is chosen such that all possible processes are represented by the same activity network. Differences between processes are determined by the customisations that they implement. The approach is illustrated through application to a small business that creates customised fashion products. We suggest that similar techniques could be applied to study intertwined design processes in more complex domains.The case study was carried out as part of Considerate Design for Personalised Fashion funded by the EPSRC/AHRC Design in the 21st century programme. The context of a multi-project environment was analysed as part of the EU Framework 7 CONVERGE project CP-FP 228746-2.Post-prin

    Modelling iteration in engineering design

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    This paper examines design iteration and its modelling in the simulation of New Product Development (NPD) processes. A framework comprising six perspectives of iteration is proposed and it is argued that the importance of each perspective depends upon domain-specific factors. Key challenges of modelling iteration in process simulation frameworks such as the Design Structure Matrix are discussed, and we argue that no single model or framework can fully capture the iterative dynamics of an NPD process. To conclude, we propose that consideration of iteration and its representation could help identify the most appropriate modelling framework for a given process and modelling objective, thereby improving the fidelity of design process simulation models and increasing their utility

    Model granularity in engineering design – concepts and framework

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    In many engineering design contexts models are indispensable. They offer decision support and help tackle complex and interconnected design projects, capturing the underlying structure of development processes or resulting products. Because managers and engineers base many decisions on models, it is crucial to understand their properties and how these might influence their behaviour. The level of detail, or granularity, of a model is a key attribute that results from how reality is abstracted in the modelling process. Despite the direct impact granularity has on the use of a model, the general topic has so far only received limited attention and is therefore not well understood or documented. This article provides background on model theory, explores relevant terminology from a range of fields and discusses the implications for engineering design. Based on this, a classification framework is synthesised, which outlines the main manifestations of model granularity. This research contributes to theory by scrutinising the nature of model granularity. It also illustrates how this may manifest in engineering design models, using Design Structure Matrices as an example, and discusses associated challenges to provide a resource for modellers navigating decisions regarding granularity.This work was supported by an Industrial CASE studentship funded by the UK Engineering and Physical Sciences Research Council and BT [EP/K504282/1]

    Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

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    Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

    Testing in the incremental design and development of complex products

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    Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested

    Detection of Echinococcus multilocularis in Carnivores in Razavi Khorasan Province, Iran Using Mitochondrial DNA

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    Echinococcus multilocularis causes alveolar echinococcosis, a serious zoonotic disease present in many areas of the world. The parasite is maintained in nature through a life cycle in which adult worms in the intestine of carnivores transmit infection to small mammals, predominantly rodents, via eggs in the feces. Humans may accidentally ingest eggs of E. multilocularis through contact with the definitive host or by direct ingestion of contaminated water or foods, causing development of a multivesicular cyst in the viscera, especially liver and lung. We found adult E. multilocularis in the intestine and/or eggs in feces of all wild carnivores examined and in some stray and domestic dogs in villages of Chenaran region, northeastern Iran. The life cycle of E. multilocularis is being maintained in this area by wild carnivores, and the local population and visitors are at risk of infection with alveolar echinococcosis. Intensive health initiatives for control of the parasite and diagnosis of this potentially fatal disease in humans, in this area of Iran, are needed

    AP2γ: a new player on adult hippocampal neurogenesis regulation

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    Since the recognition that the mammalian brain retains the ability to generate newborn neurons with functional relevance throughout life, the matrix of molecular regulators that govern adult neurogenesis has been the focus of much interest. In a recent study published in Molecular Psychiatry, we demonstrate Activating Protein 2γ (AP2γ), a transcription factor previously implicated in cell fate determination in the developing cortex, as a novel player in the regulation of glutamatergic neurogenesis in the adult hippocampus. Using distinct experimental approaches, we showed that AP2γ is specifically present in a subpopulation of transient amplifying progenitors, where it acts as a crucial promoter of proliferation and differentiation of adult-born glutamatergic granule neurons. Strikingly, deficiency of AP2γ in the adult brain compromises the generation of new glutamatergic neurons, with impact on the function of cortico-limbic circuits. Here, we share our view on how AP2γ integrates the transcriptional orchestration of glutamatergic neurogenesis in the adult hippocampus, and consequently, how it emerges as a novel molecular candidate to study the translation of environmental pressures into alterations of brain neuroplasticity in homeostatic, but also in neuropathological contexts.Bial Foundation (427/14); Northern Portugal Regional Operational Programme (NORTE 2020); European Regional Development Fund (FEDER) (projects NORTE-01-0145-FEDER-000013 e NORTE-01-0145-FEDER-000023); Competitiveness Factors Operational Programme (COMPETE)info:eu-repo/semantics/publishedVersio

    On the integration of product and process models in engineering design

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    Models of products and design processes are key to interacting with engineering designs and managing the processes by which they are developed. In practice, companies maintain networks of many interrelated models which need to be synthesised in the minds of their users when considering issues that cut across them. This article considers how information from product and design process models can be integrated with a view to help manage these complex interrelationships. A framework highlighting key issues surrounding model integration is introduced and terminology for describing these issues is developed. To illustrate the framework and terminology, selected modelling approaches that integrate product and process information are discussed and organised according to their levels and forms of integration. Opportunities for further work to advance integrated modelling in engineering design research and practice are discussed

    Engineering improved ethylene production: Leveraging systems Biology and adaptive laboratory evolution

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    Ethylene is a small hydrocarbon gas widely used in the chemical industry. Annual worldwide production currently exceeds 150 million tons, producing considerable amounts of CO2 contributing to climate change. The need for a sustainable alternative is therefore imperative. Ethylene is natively produced by several different microorganisms, including Pseudomonas syringae pv. phaseolicola via a process catalyzed by the ethylene forming enzyme (EFE), subsequent heterologous expression of EFE has led to ethylene production in non-native bacterial hosts including E. coli and cyanobacteria. However, solubility of EFE and substrate availability remain rate limiting steps in biological ethylene production. We employed a combination of genome scale metabolic modelling, continuous fermentation, and protein evolution to enable the accelerated development of a high efficiency ethylene producing E. coli strain, yielding a 49-fold increase in production, the most significant improvement reported to date. Furthermore, we have clearly demonstrated that this increased yield resulted from metabolic adaptations that were uniquely linked to the EFE enzyme (WT vs mutant). Our findings provide a novel solution to deregulate metabolic bottlenecks in key pathways, which can be readily applied to address other engineering challenges
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