Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib therapy. It is therefore critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified a long non-coding RNA referred to as lncRNA-SRLR (sorafenib resistance-associated lncRNA in RCC) that is upregulated in intrinsically sorafenib-resistant RCCs. lncRNA-SRLR knockdown sensitized nonresponsive RCC cells to sorafenib treatment, whereas the overexpression of lncRNA-SRLR conferred sorafenib resistance to responsive RCC cells. Mechanistically, lncRNA-SRLR directly binds to NF-κB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance. A STAT3 inhibitor and IL-6-receptor antagonist both restored the response to sorafenib treatment. Moreover, a clinical investigation demonstrated that high levels of lncRNA-SRLR correlated with poor responses to sorafenib therapy in RCC patients. Collectively, lncRNA-SRLR may serve as not only a predictive biomarker for inherent sorafenib resistance but also as a therapeutic target to enhance responses to sorafenib in RCC patients.

include safety and reliability based design and operations of large marine and offshore systems, probabilistic and non-probabilistic safety analysis and decision making, port safety assessment and analysis of safety-critical systems. He is currently directing a marine technology research group of 14 doctoral and postdoctoral members at Liverpool. *Corresponding author. Continued next page Use of fuzzy logic approaches to safety assessment in maritime engineering applications No. A5 2004 Journal of Marine Engineering and Technology 45Use of fuzzy logic approaches to safety assessment in maritime engineering applications 46

Computational Fluid Dynamics has been introduced to analyze the hemodynamics of intracranialaneurysm. This study aims to produce a critical assessment to evaluate the risk of bifurcation type MCA aneurysms. Methods: A series of in-vitro MCA models were designed with aspect ratio 0.8-3 and the aneurysm's size was selected 3-10 mm. Energy loss (EL) was calculated. The EL was indicated that the energy balance when flow pass through the aneurysm, we hypothesized it as a critical state. Once, EL was developed to be higher than the critical EL, the surplus of power must be transferred to harm lumen surface, here a range of hemodynamic-related factor mightbe identified to predict rupturerisk. To confirm our hypothesis, two ruptured MCA aneurysms which had suffered from two stage growth and finally ruptured, and five unruptured MCA aneurysms were analyzed. Results: The EL of in-vitro models were calculated at each aspect ratio. The EL of ruptured aneurysm increased to 2 times beyond the EL range of the in-vitro models. Contrarily, after its rupture, the EL dropped dramatically to values lower than that of the in-vitro group. The result indicated that high flow energy was concentrated inside the aneurysm before rupture, and that hemodynamic power was released after SAH. The energy loss calculated from other five unruptured aneurysms appeared lower than that of the in-vitro group; below the critical EL. Conclusion: When the EL is observedto increase rapidly at the follow-up growth aneurysm, it may be an indication of the higher risk of aneurysm rupture. The EL of the in-vitro group may be used as a critical assessment tool to evaluate the rupture risk of MCA aneurysms. FL091-Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clipping or coiling of a ruptured cerebral aneurysm. Results from the International Subarachnoid Aneurysm Trial