The influence of surface clinker on the crustal structures and dynamics of 'a'ā lava flows.

Surface structures on 'a'ā and blocky lavas reflect the internal flow dynamics during emplacement and also influence the dynamics of developing flows. To investigate the effects of brittle, clinkery 'a'ā flow crusts on flow dynamics and surface structures, we conducted sand and silicone laboratory experiments that simulated the advance of lava into a preexisting channelized flow with a surface crust. Experiments carried out with relatively thin crusts produced apparently ductile surface deformation structures, while thick crusts behaved dominantly in a brittle manner. Increased crustal thickness led to increased strength under compression but favored more disruption under tension, as the flow core welled up through tensile fractures, entraining crustal material. At lava flow fronts, upwelling and entrainment would increase heat losses by radiation and advection, respectively, resulting in a positive‐feedback cooling loop. Fracturing caused heterogeneous crustal distribution near the flow front, which resulted in lobate flow advance, despite the absence of the viscoelastic layer that has previously been inferred as the primary control on flow advance and lobe formation. We therefore conclude that the influence of a purely brittle crust on the dynamics and surface morphologies of lava flows is more significant than often thought. All of the surface structures produced in the experiments have been observed on lavas or glaciers and many also on landslides and debris flows, suggesting the results can assist in the understanding of a range of natural flows

K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways

Introduction: Although KRAS mutations in NSCLC have been considered mutually exclusive driver mutations for a long time, there is now growing evidence that KRAS-mutated NSCLC represents a genetically heterogeneous subgroup. We sought to determine genetic heterogeneity with respect to cancer-related co-mutations and their correlation with different KRAS mutation subtypes. Methods: Diagnostic samples from 4507 patients with NSCLC were analyzed by next-generation sequencing by using a panel of 14 genes and, in a subset of patients, fluorescence in situ hybridization. Next-generation sequencing with an extended panel of 14 additional genes was performed in 101 patients. Molecular data were correlated with clinical data. Whole-exome sequencing was performed in two patients. Results: We identified 1078 patients with KRAS mutations, of whom 53.5% had at least one additional mutation. Different KRAS mutation subtypes showed different patterns of co-occurring mutations. Besides mutations in tumor protein p53 gene (TP53) (39.4%), serine/threonine kinase 11 gene (STK11) (19.8%), kelch like ECH associated protein 1 gene (KEAP1) (12.9%), and ATM serine/threonine kinase gene (ATM) (11.9%), as well as MNNG HOS Transforming gene (MET) amplifications (15.4%) and erb-b2 receptor tyrosine kinase 2 gene (ERBB2) amplifications (13.8%, exclusively in G12C), we found rare co-occurrence of targetable mutations in EGFR (1.2%) and BRAF (1.2%). Whole-exome sequencing of two patients with co-occurring phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation revealed clonality of mutated KRAS in one patient and subclonality in the second, suggesting different evolutionary backgrounds. Conclusion: KRAS-mutated NSCLC represents a genetically heterogeneous subgroup with a high frequency of co-occurring mutations in cancer-associated pathways, partly associated with distinct KRAS mutation subtypes. This diversity might have implications for understanding the variability of treatment outcome in KRAS-mutated NSCLC and for future trial design. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc