Radiation is an important therapeutic strategy for hepatocellular (HCC). In this study, we evaluated the role of the dual PI3K/mTOR inhibitor, PKI-587, on radiosensitization of HCC and its possible mechanism. MTT, colony formation, flow cytometry, and immunofluorescence were used to analyze the proliferation, cell cycle, formation of residual γ-H2AX foci, and apoptosis of HCC cells. A SK-Hep1 xenograft HCC model was used to assess the effects of PKI-587 in combination with ionizing radiation in vivo. The activation levels of PI3K/AKT/mTOR and DNA damage repair pathways and their downstream effector molecules were detected with Western blot. It was found that PKI-587 sensitized HCC cells to radiation by increasing DNA damage, enhancing G0/G1 cell-cycle arrest, and inducing apoptosis. In vivo, the combination of radiation with PKI-587 significantly inhibited tumor growth. These findings suggest the usefulness of PKI-587 on radiosensitization of HCC cells by inhibiting the PI3K/AKT/mTOR and DNA damage repair pathways. The combination of ionizing radiation and PKI-587 may be a strategy to improve the efficacy of treating HCC.
Purpose
To promote the development of renewable energy, the Chinese Government adopts the policy of Feed-in Tariff and subsidy. However, the high purchase price and the intermittence limit the development of renewable energy source electricity (RES-E). The purpose of this paper is to discuss the pricing strategy for system operators to stimulate the development of the RES-E industry under the scenario of uncertain supply and demand.
Design/methodology/approach
The authors establish a two-echelon supply chain investment model led by a power grid operator considering the uncertainties in both demand and supply, and study the impact of the power purchase price designed by a system operator using Stackelberg’s model.
Findings
There is an optimal capacity for RES-E generators, that is, independent of the market demand. Besides, the optimal order of grid operators is independent of the uncertain RES-E supply and the purchase price of fossil fuel. By properly setting the purchase prices, the system operator can stimulate the capacity investment in renewable energy. Finally, increasing the punishment in power shortage can stimulate the capacity investment in RES-E under certain conditions.
Practical implications
The result of this paper can mitigate the phenomenon of power abandonment in the RES-E industry and promote the grid integration of RES-E.
Originality/value
Both uncertain demand and supply are considered in this paper. A heuristic algorithm is provided to compute the optimal purchase price combination.
With significance in improving and developing local design culture as well as in supplementing global design history, this essay describes a study on the past and a clear prediction of the future by exploring Taiwan’s design history from approximately the 1960s to 2020 based on the evolution of theme, diversity, and sustainability. In this research, the Python programming language is used to apply three algorithms of term frequency–inverse document frequency (TF-IDF), Simpson’s diversity index (SDI), and latent Dirichlet allocation (LDA) to conduct a text exploration of design journals. The results show the following: in the 1960s–1980s, the evolution of theme focused on evaluation strategies, technical practices, and foreign cultures, on digital design, multiculturalism, and design aesthetics in the 1990s, and on emotional human factors, intelligent technology, and local culture since the beginning of the 21st century. Local culture and intelligent technology are the main driving forces of the current design industry. Regarding diversity, after a period of rapid change and stable rising, it has shown a downward trend in recent years. This indicates that current design needs to be stimulated by external environmental variations. Sustainability was focused on technology, the market, and education during the 1960s–1980s; on consumers, design education, and eco-design during the 1990s; and on integration across fields during the 2000s–2020. In order to gain a wider perspective of the complete design context of Chinese culture, the results show the current and future trends of the academic community, in addition to a reference for the study of the design histories of other areas in the world.
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