Depressurization of hydrate-bearing sediments (HBS) can cause the movement of fine particles, and in turn, such fines migration affects fluid flow and mechanical behavior of sediments, ultimately affecting long-term hydrocarbon production and wellbore stability. This study investigated how and to what extent depressurization of HBS causes fines migration using X-ray computed tomography (CT) imaging. Methane hydrate was synthesized in sediments with 10% fines content (FC), composed of sands with silt and/or clay, and the hydrate-bearing samples were stepwisely depressurized while acquiring CT images. The CT images were analyzed to quantify the spatial changes in FC in the host sediment and thus to capture the fines migration during depressurization. It was found that the FC changes began occurring from the hydrate dissociation regions. This confirms that the multiphase flow caused by depressurization accompanies fines migration. Depressurization of HBS with a hydrate saturation of ~20–40% caused FC reduction from ~10% to ~6–9%, and the extent of fines migration differed with the particle sizes of the host sands and the types of fines. It was found that fines migration was more pronounced with coarse sands and with silty fines. Such observed level of FC reduction is estimated to increase sediment permeability by several factors based on the Kozeny-type permeability model. Our results support the notion that the extent of fines migration and its effect on fluid flow behavior need to be assessed in consideration of physical properties of host sediment and fine particles to identify optimum depressurization strategies.

We validate a coupled flow-geomechanics simulator for gas hydrate deposits, named T+MAM, performing two meter-scale laboratory experiments of gas hydrates for production by depressurization, replicating the gas hydrate deposit in the Ulleung Basin, East Sea, South Korea. The first experiment with a sand-only specimen is a 1D 1 m-scale depressurization test based on the excess gas method, which represents the grain coating hydrate growth. On the other hand, the second is a 3D 1.5 m-scale test with the excess water method for a sand–mud alternating layer system, representing the pore filling hydrate growth. We measure production and displacement at the top with different depressurization levels. In particular, the 3D test exhibits high coupling strength of substantial deformation induced by incompressibility of water and high deformability of the specimen. For validation, we match pressure, flow rate, and displacement between the experimental data and numerical results. Thus, we identify that T+MAM is a reliable simulator, which can be applied to fields in both permafrost and deep oceanic hydrate deposits of strongly coupled flow and geomechanics systems. This validation also implies that other coupled simulators based on the same coupling formulation as T+MAM can be validated when individual flow and geomechanics simulators are stable and reliable.

The clinical utility of approved EGFR small-molecule kinase inhibitors is plagued both by toxicity against wild-type EGFR and by metastatic progression in the central nervous system, a disease sanctuary site. Here, we report the discovery and preclinical efficacy of GNS-1486 and GNS-1481, two novel small-molecule EGFR kinase inhibitors that are selective for T790M-mutant isoforms of EGFR. Both agents were effective in multiple mouse xenograft models of human lung adenocarcinoma (T790M-positive or -negative), exhibiting less activity against wild-type EGFR than existing approved EGFR kinase inhibitors (including osimertinib). In addition, GNS-1486 showed superior potency against intracranial metastasis of EGFR-mutant lung adenocarcinoma. Our results offer a preclinical proof of concept for new EGFR kinase inhibitors with the potential to improve therapeutic index and efficacy against brain metastases in patients. Cancer Res; 77(5); 1200-11. ©2017 AACR.