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In recent years, advances in information technology and enterprise engineering have revolutionised the way businesses are conducted. Enterprises. are complicated organisations consisting of 'artefacts' (enterprise structure, activities, processes, information, resources, behaviour, goals, and constraints) that must be coordinated, planned and engineered to accomplish the enterprise goals. Enterprise engineering is an engineering approach comprised of techniques, methods, and infrastructures to aid the design, analysis, and implementation of an enterprise system. However, many modellers forgo the enterprise modelling methods and techniques and use localised ad-hoc and point solutions that are not amenable for enterprise infrastructure design. The current methods and techniques available are ill-equipped to model the holistic requirements oftoday's complex enterprises. .' This research adopts the PAM (problem Articulation Method), rooted in semiotics, a study of signs, symbols, language and information. PAM offers a suite of techniques, which enables the articulation and analysis of business, technical and organisational requirements, delivering a rigorous enterprise infrastructure to support the model. The method works by eliciting and formalising project planning and modelling (processes, .activities, relationships, responsibilities, communications, resources, agents, dependencies and constraints), where the abstractions are mapped to represent the manifestation ofthe 'actual' enterprise. ~ .,J The proposed enterprise framework incorporates PAM and MEASUR (Methods for Eliciting Analysing and Specifying Users Requirements) a suite of semiotics methods to model the agent's ontological relationships, defining its meaning (semantics) to improve the analytical capability of the model and elicit the normative behaviours of agents to enrich the enterprise model. The PAM method has been further extended to examine the method relevance and significance in dealing with innovation in the modelling and planning of complex enterprise projects. The PAM conceptual model created is subsequently analysed, tested and verified using an off-the-shelf discreteevent simulation software, to be modelled dynamically. The simulation models are also validated by the domain experts from the respective organisations to assess the consistency, coherence and logical correctness of the 'model. This modelling approach contributed to the further development of the PAM theories, methods and techniques and represents a significant improvement to facilitate enterprise infrastructure planning and in so doing, exploit the technological, business and organisational effectiveness.

The formation of the root epidermis in Arabidopsis provides a simple and elegant model for the study of cell fate specification. An epidermal cell develops as a root hair cell when it overlies two cortical cells, and develops as a root non-hair cell when it overlies a single cortical cell. A network of transcription factor proteins, WEREWOLF (WER), GLABRA3 (EGL3), ENHANCER OF GLABRA3 (EGL3), and TRANSPARENT TESTA GLABRA1 (TTG1), promote the non-hair cell fate through the activation of GLABRA2 (GL2) gene expression in the non-hair cell position, and promote the hair cell fate through the activation of CAPRICE (CPC) gene expression in the non-hair cell position. The CPC protein acts through a mechanism of lateral inhibition to regulate gene expression in the neighboring hair cells by the direct movement of the CPC protein from non-hair cells to hair cells and throughout the epidermis. We have identified four CPC homologs, TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC 1, 2 and 3 (ETC1, ETC2 and ETC3), that are able to functionally substitute for the CPC in root epidermal patterning. CPC, TRY and ETC1 are expressed in the non-hair cell position and act in a partially redundant manner to regulate cell fate specification in the root, whereas ETC2 and ETC3 are not expressed in the root and do not have a role in root epidermal patterning. We identify a new regulator of root epidermal patterning, TRANSPARENT TESTA GLABRA2 (TTG2), that enhances a cpc mutant phenotype. We find that the TTG2 and GL2 and genes positively regulate TRY gene expression, but do not regulate CPC or ETC1 gene expression in the non-hair cell position. Thus, we propose that TTG2 and GL2 act in a secondary step to initiate and maintain lateral inhibition signaling through the regulation of TRY gene expression in the root epidermis.

Neutrophils are critical and short lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Autophagy was described as a critical process in HSC differentiation and in memory- and regulatory T cells, where it prevents excessive glycolysis and maintains lipid metabolic homeostasis. In the myeloid lineage, an essential role for autophagy is to prevent pro-inflammatory macrophage polarization and to limit glycolytic metabolism of acute myeloid leukemia. While these studies provide robust in vivo evidence for the relevance of autophagy in the differentiation of hematopoietic and immune cells, the targets and mechanisms of autophagy remain elusive. Here, we show that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo. Atg7 -deficient neutrophil precursors had increased glycolytic activity but impaired mitochondrial respiration, decreased ATP production and accumulated lipid droplets. Inhibiting autophagy-mediated lipid degradation or fatty acid oxidation alone was sufficient to cause defective differentiation, while administration of fatty acids or pyruvate for mitochondrial respiration rescued differentiation in autophagy deficient neutrophil precursors. Together, we show that autophagy-mediated lipolysis provides free fatty acids to support a mitochondrial respiration pathway essential to neutrophil differentiation. Evidence presented here also contributed to studies on autophagy-mediated metabolic homeostasis in HSCs, Treg cells and myeloid leukemia, suggesting that this pathway may act broadly during differentiation.