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An electrochemical metallization memristor based on Zr0.5Hf0.5O2 film and an active Cu electrode with quantum conductance and neuromorphic behavior has been reported in this work. After electroforming in the Cu/Zr0.5Hf0.5O2/Pt device, linear conductance characteristics in low resistance states were found and the stepwise changes of conductance with the order of G0 ((=2e2)/h) multilevel states were obtained by varying pulse amplitude, width and adjacent-pulse time interval, which is beneficial for backpropagation learning algorithms belonging to deep neural networks, essentially using memristors as vector–matrix multiplication accelerators in image processing. The gradual resistance tuning served as the basis of memory and learning. Under the coactivity of pre- and post-synaptic spikes, bidirectional long-term Hebbian plasticity modulation was realized. The temporal difference, spike rate and size of the top and bottom electrode pulse voltage can strongly affect the sign and degree of Hebbian plasticity. Moreover, the quantum conductance phenomenon was ascribed to interstitial Cu in the dielectric layer forming single- and multi-atom chains. The results can provide multilevel storage and next-generation parallel neuromorphic computing architecture, promoting the development of functional plastic electronic synapses.

Resistive random-access memory plays a key role in non-volatile and neuromorphic artificial electronic devices. In this work, we fabricated Ta/TaOx/AlN/Pt resistive memory devices with the inserted AlN layer to improve the performance. The devices have better stability, lower threshold voltage (≈0.37 V), longer retention time (>104 s), and faster switching speed (9 ns) than those without the AlN film layer. More importantly, when different pulse parameters were applied, two phenomena, abrupt jumps in conductance and gradual change in conductance, were obtained. Furthermore, the biological synaptic functions were simulated, including the spiking-time-dependent plasticity and the paired-pulse facilitation. The Ta/TaOx/AlN/Pt resistive memory devices offer promising features; hence, they are good candidates for next-generation electronic devices for chip systems.

Objective: Heat Shock Protein 90 (Hsp90) is a molecular chaperone that mediates the post-translational stability of its protein substrates, many of which are onco-proteins. Hsp90 is emerging as an important target for cancer therapy because its inactivation may abrogate multiple signaling pathways simultaneously, irrespective of the mutational status of proteins involved. We disclose here our clinical candidate WXFL1024H251, a novel second-generation small-molecule Hsp90 inhibitor with a chemical structure unrelated to the first generation, the ansamycin family of Hsp90 inhibitors. Method: The anti-proliferative activity of WXFL1024H251 was evaluated in a variety of cancer cell lines in a 96-hour viability assay. QW, Q2W or TIW intravenous administration of at doses of 5~50 mg/kg was used to evaluate the in vivo anti-tumor activity of WXFL1024H251 in BT474 cell line-derived xenograft (CDX) breast cancer model. Effects of WXFL1024H251 on HSP90 function were assessed by western blot analysis of PD markers HSP70, Her2 and p-Her2 in the BT474 tumors. Result: A panel of 20 cancer cell lines were screened for sensitivity to WXFL1024H251. Proliferation of 2 cancer cell lines A549 and BT474 were potently inhibited by WXFL1024H251, with IC50 of 0.007 μM and 0.009 μM, respectively. A549 cell line has KRAS mutation and medium to high EGFR expression. BT474 is an ER+ and ERBB2+ breast cancer cell line. In the BT474 tumor model, 3 week treatment with WXFL1024H251 showed good antitumor efficacy with T/C values of 36% at 7.5 mg/kg Q2W and 45% at 10 mg/kg QW; toxicity were acceptable with both dosing regiments. Conclusion: These preclinical studies showed good antitumor efficacy of WXFL1024H251, which was associated with client protein maturation and HSP70 up-regulation in the tumor tissue. WXFL1024H251 may represent a novel promising clinical antitumor agent for treating breast cancer and other cancer types with high expression of HSP90. Citation Format: Xiaobing yan, Charles Z. Ding, Lihong Hu, Wei Huang, Shuhui Chen, Dongdong Wu, Jiahu Wu, Guoqiang Ma, Qiyao Zhang, Rui Gao, Yusong Zhu, Tiantian Dong, Yizhong Zhu, Caixia Yan, Yan Yan. Preclinical evaluation of WXFL1024H251, a potent second-generation HSP90 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1672.