The theory of international business: the role of economic models

This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

Anisotropic Colossal Magnetoresistance Effects in Fe_{1-x}Cu_xCr_2S_4

A detailed study of the electronic transport and magnetic properties of Fe$_{1-x}$Cu$_x$Cr$_2$S$_4$ ($x \leq 0.5$) on single crystals is presented. The resistivity is investigated for $2 \leq T \leq 300$ K in magnetic fields up to 14 Tesla and under hydrostatic pressure up to 16 kbar. In addition magnetization and ferromagnetic resonance (FMR) measurements were performed. FMR and magnetization data reveal a pronounced magnetic anisotropy, which develops below the Curie temperature, $T_{\mathrm{C}}$, and increases strongly towards lower temperatures. Increasing the Cu concentration reduces this effect. At temperatures below 35 K the magnetoresistance, $MR = \frac{\rho(0) - \rho(H)}{\rho(0)}$, exhibits a strong dependence on the direction of the magnetic field, probably due to an enhanced anisotropy. Applying the field along the hard axis leads to a change of sign and a strong increase of the absolute value of the magnetoresistance. On the other hand the magnetoresistance remains positive down to lower temperatures, exhibiting a smeared out maximum with the magnetic field applied along the easy axis. The results are discussed in the ionic picture using a triple-exchange model for electron hopping as well as a half-metal utilizing a band picture.Comment: some typos correcte

In direct breach of managerial edicts: A practice approach to creative deviance in professional service firms

Drawing on practice as a meta-theoretical lens, we explore creative deviance (CD): wilful violation of managerial orders by employee(s) to pursue creative ideas. Data for our inquiry comes from in-depth interviews with middle managers and employees in two professional service firms (PSFs). We argue that two distinct organising processes are necessary for the emergence of CD in practice: organising configuration and formalisation of R&D processes. We develop these dimensions to produce a typology of interrelated ideal types of outcomes when employees are explicitly instructed to stop pursuing an idea. We found three salient organising practices (technical concerns for efficiency and metrics, suppression of metistic knowledge and disjointed managerial responses to violations of sanctioned organising procedures), which may operate in combination or serially, to foster CD in practice. We conclude with some key implications for the theory and practice of creativity in PSFs. © 2018 RADMA and John Wiley & Sons Ltd

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma

Background: An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.Materials and methods: Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).Results: In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.Conclusions: Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Re-inventing artisanal knowledge and practice: a critical review of innovation in a craft-based industry

This paper presents a critical review of the ways in which the specialised knowledge and working practices of craft-based industries have been transformed in the context of broader processes of industrialisation and global competition. The opening section makes the case for artisanal knowledge as a ‘Cinderella’ subject that remains important yet largely uncharted territory for innovation researchers. It is followed by a critical review of existing empirical and theoretical studies that have examined the reproduction and reinvention of artisanal knowledge. The review concludes that valuable insights remain obscured due to the way in which this literature is distributed across discrete disciplines with little evidence of cross-fertilisation or integration. Several common themes emerge, which provide the basis for an outline theoretical framework. The central arguments are illustrated with reference to a case-based analysis of the technological and social innovations that have taken place in English farmhouse cheesemaking over an extended period, from the pre-industrial era to the beginning of the present century. The concluding section considers how more nuanced understandings of artisanal knowledge and practice might enhance innovation theory and contribute to the continued flourishing of craft-based industries

"They go for gender first"

There have been many recent media reports about the online harassment of women journalists working in technology, particularly the video gaming industry. However, little research has focused on this aspect, by looking at specific occupations, or analysing the implications for women and society. This paper is a feminist study of the experiences of sexist abuse of a sample of women journalists writing about technology. It is a commentary on the results of a questionnaire-based study of 102 women (and their approximately 300 comments) that work in what has emerged as one of the frontlines of the struggle for gender equality. The research looks at the extent of the abuse, the harm it causes and how women are reacting to it. Most of the participants have experienced abuse, many have changed their working practices and some have disguised their identity to avoid it. An examination of their comments suggests that sexist abuse is now often normalised, alongside a new kind of "invisible" feminism. It also reveals a mood of defiance and an appetite for radical change to address the problems of exclusion and loss of identity. Overall, results indicate that the abuse is damaging women’s lives and impacting journalism and society in a negative way

Outside in-group and out-group identities? Constructing male solidarity and female exclusion in UK builders’ talk

This article examines the spoken interactions of a group of British construction workers to discover whether it is possible to identify a distinctive ‘builders’ discourse’. Given that builders work for a mostly all-male profession (Curjao, 2006), we ask whether the ways in which male builders converse with each other while ‘on the job’ can be held in any way responsible for the under-representation of women within this major occupational sector in the UK. This article reports on a case study of the conversations of three white, working-class, male builders, which took place while travelling in a truck between different building sites. This forms part of a larger ethnographic study of builders’ discourse in different work locations. The analysis shows that male builders are highly collaborative in constructing narratives of in-group and out-group identities (Duszak, 2002; Tajfel, 1978). Various other male groups are demonized in these conversations: Polish immigrant builders, rude clients and rival builders. However, there is almost no reference to women. The article concludes that women are viewed as so unthreatening to male ascendancy in the building industry that they do not even feature within the ‘out-group’