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The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively. A fluorescence microscope was applied to analyze platelet spreading. SC99 inhibited the phosphorylation of JAK2 and STAT3 in human platelets but had no effects on the phosphorylation of AKT, p65 or Src, all of which are involved in platelet activation. Further studies revealed that SC99 inhibited human platelet aggregation induced by collagen and thrombin in a dose-dependent manner. SC99 inhibited thrombin-induced P-selectin expression and fibrinogen binding to single platelets. Moreover, SC99 inhibited platelet spreading on fibrinogen and clot retraction mediated by outside-in signaling. SC99 inhibited platelet aggregation in mice but it did not significantly prolong the bleeding time. Taken together, the present study revealed that SC99 inhibited platelet activation and aggregation as a STAT3 inhibitor. This agent can be developed as a promising treatment for thrombotic disorders.

With the help of modeling by ANSYS and application of finite element method, 3D static analysis of GIS pipe shell, the self-vibration analysis of the whole structure are carried out in this thesis. The basic principles of modal analysis in ANSYS are introduced. After establishing the integral finite element modal considering the self-weight of GIS pipe shell in ANSYS, the structural model analysis is carried, the top 30 order models are obtained, and the former five-order vibration mode are listed in this thesis. The analysis about the free vibration characters of the GIS pipe shell structure shows that the lateral stiffness in two direction of the structure is relatively uniform, and the structure is comparatively regular, with small torsional rigidity. Also it suggests that the stiffness of side force resistance and torsion resisting stiffness should be improved during the design process.

Dynamic Difficulty Adjustment (DDA) of Game AI aims at creating a satisfactory game experience by dynamically adjusting intelligence of game opponents. It can provide a level of challenge that is tailored to the player's personal ability. The Monte-Carlo Tree Search (MCTS) algorithm can be applied to generate intelligence of non-player characters (NPCs) in video games. And the performance of the NPCs controlled by MCTS can be adjusted by modulating the simulation time of MCTS. Hence the approach of DDA based on MCTS is proposed based on the application of MCTS. In this paper, the prey and predator game genre of Pac-Man is used as a test-bed, the process of creating DDA based on MCTS is demonstrated and the feasibility of this approach is validated. Furthermore, to increase the computational efficiency, an alternative approach of creating DDA based on knowledge from MCTS is also proposed and discussed.