Modularisation strategies in the AEC industry:a comparative analysis

Many industries have benefited from modularisation; while in the architecture, engineering and construction (AEC) industry, the concept of modularisation is associated with dimensional coordination. This has added to an already extensive list of challenges due to market size and the concept of economies of scale in AEC industry, to name but a few. Moreover, there is a myth that the AEC industry is bound to stay associated with build-to-order or made-to-order approach caused the AEC industry to restrict modularisation to the component level. This changes the balance in favour of what this paper calls a bottom-up approach. On the other hand, a valid alternative strategy–referred to in this study as top-down strategy–remains very much underexploited. The clients, therefore, do not have a neutral means by which they can assess which strategy is in their best interest. Likewise, if a construction company plans to make a strategic move towards the principles of modularisation and off-site manufacturing, they do not have clear decision support tools. This study investigates these two main modularisation strategies in the AEC industry to provide some examples of successful cases regarding how, when and where such strategy have been applied by different construction companies in different cases. The collected and collated empirical data and the results from the interviews will help clients and companies to analyse their own cases and make operational decisions on how, when and where to best utilise the bottom-up and top-down modularisation techniques while considering the pros and cons of such decisions

New complex product introduction by means of product configuration

Configuration systems have widely been applied to efficiently address the customization responsiveness squeeze of companies dealing with Mass Customization. Over time, several frameworks have been introduced to enable their systematic planning, analyses, development and implementation. Traditional research has thereby either focused on defining modelling techniques for the configuration model of stable products, on improved configuration algorithms, or on the impact of configurators on companies ’ operations. However, little attention has yet been paid how the growing need for product innovation can effectively been supported. Especially for engineering companies moving towards Mass Customization, compared to mass producers the challenges caused by the complexity of their products and by the highly uncertain markets are much higher. This study develops and validates a framework which enables the use of configuration systems along the introduction of complex products. It in particular examines (1) what are suitable development strategies for configuration systems during product innovation, (2) how product development and configuration development can be aligned and managed, and (3) how supplier integration can be achieved

Etiology-independent activation of the LTβ-LTβR-RELB axis drives aggressiveness and predicts poor prognosis in Hepatocellular carcinoma

BACKGROUND AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver tumor with an increasing incidence worldwide. HCC is a heterogeneous malignancy and develops usually in a chronically injured liver. The nuclear factor kappa B (NF-κB) signaling network consists of a canonical and a non-canonical branch. An activation of canonical NF-κB in HCC is documented. However, a functional and clinically relevant role of non-canonical NF-κB and its downstream effectors is not established. APPROACH RESULTS: Four human HCC cohorts (total n=1,462) and four mouse HCC models were assessed for expression and localization of NF-κB signaling components and activating ligands. In vitro, NF-κB signaling, proliferation and cell death were measured, proving a pro-proliferative role of RELB activated via NIK. In vivo, Lymphotoxin beta (LTβ) was identified as predominant inducer of RELB activation. Importantly, hepatocyte-specific RELB knockout in a murine HCC model led to a lower incidence compared to controls and lower maximal tumor diameters. In silico, RELB activity and RELB directed transcriptomics were validated on the TCGA HCC cohort using inferred protein activity and Gene Set Enrichment Analysis (GSEA). In RELB-active HCC, pathways mediating proliferation were significantly activated. In contrast to RELA, nuclear enrichment of non-canonical RELB expression identified patients with a poor prognosis in an etiology-independent manner. Moreover, RELB activation was associated with malignant features metastasis and recurrence. CONCLUSIONS: This study demonstrates a prognostically relevant, etiology-independent and cross-species consistent activation of a LTβ/LTβR/RELB axis in hepatocarcinogenesis. These observations may harbor broad implications for HCC, including possible clinical exploitation