APOBEC3 Mediates Resistance to Oncolytic Viral Therapy
MOLECULAR THERAPY-ONCOLYTICS
Authors: Huff, Amanda L.; Wongthida, Phonphimon; Kottke, Timothy; Thompson, Jill M.; Driscoll, Christopher B.; Schuelke, Matthew; Shim, Kevin G.; Harris, Reuben S.; Molan, Amy; Pulido, Jose S.; Selby, Peter J.; Harrington, Kevin J.; Melcher, Alan; Evgin, Laura; Vile, Richard G.
Abstract
Tumor cells frequently evade applied therapies through the accumulation of genomic mutations and rapid evolution. In the case of oncolytic virotherapy, understanding the mechanisms by which cancer cells develop resistance to infection and lysis is critical to the development of more effective viral-based platforms. Here, we identify APOBEC3 as an important factor that restricts the potency of oncolytic vesicular stomatitis virus (VSV). We show that VSV infection of B16 murine melanoma cells upregulated APOBEC3 in an IFN-beta-dependent manner, which was responsible for the evolution of virus-resistant cell populations and suggested that APOBEC3 expression promoted the acquisition of a virus-resistant phenotype. Knockdown of APOBEC3 in B16 cells diminished their capacity to develop resistance to VSV infection in vitro and enhanced the therapeutic effect of VSV in vivo. Similarly, overexpression of human APOBEC3B promoted the acquisition of resistance to oncolytic VSV both in vitro and in vivo. Finally, we demonstrate that APOBEC3B expression had a direct effect on the fitness of VSV, an RNA virus that has not previously been identified as restricted by APOBEC3B. This research identifies APOBEC3 enzymes as key players to target in order to improve the efficacy of viral or broader nucleic acid-based therapeutic platforms.
Off-design performance of CAES systems with low-temperature thermal storage under optimized operation strategy
JOURNAL OF ENERGY STORAGE
Authors: Guo, Huan; Xu, Yujie; Guo, Cong; Zhang, Yi; Hou, Hucan; Chen, Haisheng
Abstract
Compressed air energy storage (CAES) systems usually operate under off-design conditions due to load fluctuations, environmental factors, and performance characteristics of the system. However, the current research on off-design performance of CAES systems, especially in the aspects of advanced compressed air energy storage systems and operation strategies, is deeply insufficient. The complete off-design model of a compressed air energy storage system with thermal storage (TS-CAES) and optimal regulations by adjusting variable inlet guide vane (VIGV) and variable stator vane (VSV) is established for the first time. Using this model, we uncover the off-design characteristics common in TS-CAES systems caused by changes in load, ambient temperature, and operation type (constant pressure operation and sliding-pressure operation), and which is conducted under the optimal regulation strategy for the compression and expansion sections. It is found that system parameters fluctuate around a balance position with load fluctuation. But under the optimal operation, the fluctuation of the system efficiency and energy density is relatively small. System efficiency and energy density increase marginally with the decrease of ambient temperature, and thermal storage temperature increases linearly and markedly with rise in ambient temperature. We also found that system efficiency under constant pressure operation is decreased by 1.74 percent compared to that under sliding-pressure. This study will provide theoretical support for the design, operation, and control of TS-CAES systems.