7 research outputs found

    Impurity Oxygen-Triggered α- → β-Si<sub>3</sub>N<sub>4</sub> Phase Transformation at 1900 °C

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    Oxide additive-free α- → β-Si3N4 phase transformation of a high-purity commercial α-Si3N4 powder was investigated at 1600 to 1900 °C under a nitrogen pressure of 980 kPa. The XRD analysis revealed that the α- → β-Si3N4 phase transformation proceeded mainly at 1900 °C, and was completed by the extensive 1900 °C heat treatment for 20 h. This phase transformation temperature was 33 °C lower than the theoretical α-Si3N4 dissociation temperature and was confirmed as completely different from that often discussed for the liquid-phase sintering of α-Si3N4 powder by direct comparison with the phase transformation behavior of a reference powder, α-Si3N4 powder doped with 1 mol% Y2O3. The unique α- → β-Si3N4 phase transformation was further studied by a set of characterization techniques including elemental analysis, HAADF-STEM and STEM-EDS analyses. The results strongly suggested that the oxide additive-free α- → β-Si3N4 phase transformation was governed by the formation of a metastable solid solution between α-Si3N4 and impurity oxygen of approximately 0.6 wt%, which promoted the dissociation below the theoretical α-Si3N4 dissociation temperature to afford thermodynamically favorable β-Si3N4. Along with the β-Si3N4 formation, the impurity oxygen concentrated at the grain boundaries was released from the sample via the grain boundary diffusion to afford high-purity β-Si3N4

    Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer

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    Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide
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