Given the increasing number and severity of North Korean provocations, this article quantitatively analyses the relationship between North Korean actions and different types of events and actions taken by the international community commonly described as ‘triggers’ for these provocations. A database of 257 possible trigger events and 88 North Korean provocations, covering the period from 1 January 2012 through 21 November 2016, was developed for investigation. Statistical analyses assessed correlations between specific types of trigger events and North Korean provocations writ large as well as the specific level of provocation. The article concludes that, despite media and academic assessments to the contrary, the notional trigger events explored in this article appear to be uncorrelated with either North Korea undertaking a provocation or its level of severity. The strongest finding supports the concept of provocation cycles, in which the clearest predictor of a North Korean provocation is simply whether or not another provocation has recently taken place. Yet, the article also finds that in these situations additional provocations may more likely be of a lower level, such as short-range missile tests or limited naval incursions. International leaders’ decisions should be informed by this apparent lack of significant correlation between provocations and events such as USA–South Korean military exercises, United Nations Security Council resolutions, or a high-level US visit to the region.

<p>Supplementary Figures</p>

<div>Abstract<p>Although EGFR mutant–selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using <i>in vitro</i> models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK–ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI–resistant persister cells. Many patients with non–small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutation, who progressed on EGFR inhibitors, demonstrated increased CXCR7 expression. These data suggest that CXCR7 inhibition could considerably delay and prevent the emergence of acquired EGFR TKI resistance in EGFR-mutant NSCLC.</p>Significance:<p>Increased expression of the chemokine receptor CXCR7 constitutes a mechanism of resistance to EGFR TKI in patients with non–small cell lung cancer through reactivation of ERK signaling.</p></div>

No abstract

<p>Supplementary Figures</p>