Variability and uncertainty in empirical ground-motion prediction for probabilistic hazard and risk analyses

© The Author(s) 2015.The terms aleatory variability and epistemic uncertainty mean different things to people who routinely use them within the fields of seismic hazard and risk analysis. This state is not helped by the repetition of loosely framed generic definitions that actually inaccurate. The present paper takes a closer look at the components of total uncertainty that contribute to ground-motion modelling in hazard and risk applications. The sources and nature of uncertainty are discussed and it is shown that the common approach to deciding what should be included within hazard and risk integrals and what should be pushed into logic tree formulations warrants reconsideration. In addition, it is shown that current approaches to the generation of random fields of ground motions for spatial risk analyses are incorrect and a more appropriate framework is presented

A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity

ZIC2 mutation is known to cause holoprosencephaly (HPE). A subset of ZIC2 HPE probands harbour cardiovascular and visceral anomalies suggestive of laterality defects. 3D-imaging of novel mouse Zic2 mutants uncovers, in addition to HPE, laterality defects in lungs, heart, vasculature and viscera. A strong bias towards right isomerism indicates a failure to establish left identity in the lateral plate mesoderm (LPM), a phenotype that cannot be explained simply by the defective ciliogenesis previously noted in Zic2 mutants. Gene expression analysis showed that the left-determining NODAL-dependent signalling cascade fails to be activated in the LPM, and that the expression of Nodal at the node, which normally triggers this event, is itself defective in these embryos. Analysis of ChiP-seq data, in vitro transcriptional assays and mutagenesis reveals a requirement for a low-affinity ZIC2 binding site for the activation of the Nodal enhancer HBE, which is normally active in node precursor cells. These data show that ZIC2 is required for correct Nodal expression at the node and suggest a model in which ZIC2 acts at different levels to establish LR asymmetry, promoting both the production of the signal that induces left side identity and the morphogenesis of the cilia that bias its distribution

Genomic Targets of Brachyury (T) in Differentiating Mouse Embryonic Stem Cells

The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury targets in the mouse.Here we use chromatin immunoprecipitation and mouse promoter microarrays to identify targets of Brachyury in embryoid bodies formed from differentiating mouse ES cells. The targets we identify are enriched for sequence-specific DNA binding proteins and include components of signal transduction pathways that direct cell fate in the primitive streak and tailbud of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they are also Brachyury targets in the human. Surprisingly, we do not observe enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n) repeat sequence, which is conserved in the rat but not in human, zebrafish or Xenopus. We do not understand the significance of this sequence, but speculate that it enhances transcription factor binding in the regulatory regions of Brachyury target genes in rodents.Our work identifies the genomic targets of a key regulator of mesoderm formation in the early mouse embryo, thereby providing insights into the Brachyury-driven genetic regulatory network and allowing us to compare the function of Brachyury in different species

Marking their own homework: The pragmatic and moral legitimacy of industry self-regulation

When is industry self-regulation (ISR) a legitimate form of governance? In principle, ISR can serve the interests of participating companies, regulators and other stakeholders. However, in practice, empirical evidence shows that ISR schemes often under-perform, leading to criticism that such schemes are tantamount to firms marking their own homework. In response, this paper explains how current management theory on ISR has failed to separate the pragmatic legitimacy of ISR based on self-interested calculations, from moral legitimacy based on normative approval. The paper traces three families of management theory on ISR and uses these to map the pragmatic and moral legitimacy of ISR schemes. It identifies tensions between the pragmatic and moral legitimacy of ISR schemes, which the current ISR literature does not address, and draws implications for the future theory and practice of ISR

Geography and history matter: International business and economic geography perspectives on the spatial and historical development of multinational enterprises

Situated within the broader conference theme of historical change, this panel session brought together international business and economic geography perspectives on multinational enterprise (MNE) evolutionary trajectories. The panel session follows a series of past conference sessions aimed to increase dialogue and interaction between economic geographers and international business scholars. These included several sessions at the Royal Geographical Society and Institute of Geographer’s Annual Conference in 2010 and the Association of International Business in 2012. The aim for this conference panel session was for panellists to offer a range of empirical and conceptual observations to interrogate our existing understandings of the spatial and historical development of MNEs. While space and time often provide distinct lenses on the operations of MNEs, the panel discussed the ways in which the two can be combined to provide more nuanced conceptualisations and frameworks for analysis, which can powerfully complement existing conceptual frameworks and methodological approaches in international business. This chapter is a record of the panel session and, as such, offers a direct representation of the speakers’ presentations, their discussions and their question and answer session. The chapter begins with Martin Hess’ discussion of continuity and change in MNEs and global production networks, followed by Rudolf Sinkovics’ analysis of the uptake of economic geography work on global sourcing by international business