The attention is a scarce resource in decentralized autonomous organizations(DAOs),as their self-governance relies heavily on the attention-intensive decision-making process of“proposal and voting”.To prevent the ne...The attention is a scarce resource in decentralized autonomous organizations(DAOs),as their self-governance relies heavily on the attention-intensive decision-making process of“proposal and voting”.To prevent the negative effects of pro-posers’attention-capturing strategies that contribute to the“tragedy of the commons”and ensure an efficient distribution of attention among multiple proposals,it is necessary to establish a market-driven allocation scheme for DAOs’attention.First,the Harberger tax-based attention markets are designed to facilitate its allocation via continuous and automated trading,where the individualized Harberger tax rate(HTR)determined by the pro-posers’reputation is adopted.Then,the Stackelberg game model is formulated in these markets,casting attention to owners in the role of leaders and other competitive proposers as followers.Its equilibrium trading strategies are also discussed to unravel the intricate dynamics of attention pricing.Moreover,utilizing the single-round Stackelberg game as an illustrative example,the existence of Nash equilibrium trading strategies is demonstrated.Finally,the impact of individualized HTR on trading strategies is investigated,and results suggest that it has a negative correlation with leaders’self-accessed prices and ownership duration,but its effect on their revenues varies under different conditions.This study is expected to provide valuable insights into leveraging attention resources to improve DAOs’governance and decision-making process.展开更多
From AlphaGo to ChatGPT,the field of AI has launched a series of remarkable achievements in recent years.Analyzing,comparing,and summarizing these achievements at the paradigm level is important for future AI innovati...From AlphaGo to ChatGPT,the field of AI has launched a series of remarkable achievements in recent years.Analyzing,comparing,and summarizing these achievements at the paradigm level is important for future AI innovation,but has not received sufficient attention.In this paper,we give an overview and perspective on machine learning paradigms.First,we propose a paradigm taxonomy with three levels and seven dimensions from a knowledge perspective.Accordingly,we give an overview on three basic and twelve extended learning paradigms,such as Ensemble Learning,Transfer Learning,etc.,with figures in unified style.We further analyze three advanced paradigms,i.e.,AlphaGo,AlphaFold and ChatGPT.Second,to enable more efficient and effective scientific discovery,we propose to build a new ecosystem that drives AI paradigm shifts through the decentralized science(DeSci)movement based on decentralized autonomous organization(DAO).To this end,we design the Hanoi framework,which integrates human factors,parallel intelligence based on a combination of artificial systems and the natural world,and the DAO to inspire AI innovations.展开更多
Objective:To investigate the effects and underlying mechanism of 2-hexyl-4-pentynoic acid(HPTA),a derivative of valproic acid(VPA),on radiotherapy in breast cancer.Methods:MCF7 cells and 7,12-dimethylbenz-[α]-anthrac...Objective:To investigate the effects and underlying mechanism of 2-hexyl-4-pentynoic acid(HPTA),a derivative of valproic acid(VPA),on radiotherapy in breast cancer.Methods:MCF7 cells and 7,12-dimethylbenz-[α]-anthracene(DMBA)-induced transformed human normal breast cells(MCF10A–DMBA cells)were irradiated with 8 Gy X-rays.For both cells there were four groups:control,valproic acid(VPA)/HPTA,IR,and VPA/HPTA+IR groups.MTT and clonogenic survival assays were performed to assess cell proliferation,and comet assay was performed to evaluate DNA damage.Protein expression ofγH2AX,53BP1,Rad51,and BRCA1 was examined via immunofluorescence and immunoblotting.Cycloheximide chase and ubiquitination experiments were conducted to determine Rad51 ubiquitination.In vivo experiments involved a rat model of DMBA-induced breast cancer,with four fractionated doses of 2 Gy.Tumor tissue pathological changes andγH2AX,Rad51,and UCHL3 expression levels were measured by hematoxylin-eosin staining,immunohistochemistry,and immunoblotting.Results:Compared with the IR group,15μmol/L HPTA reduced the cell proliferation ability of irradiated MCF7 cells(t=2.16,P<0.05).The VPA/HPTA+IR group exhibited significantly increased DNA double-strand breaks relative to those in the IR group(VPA+IR vs.IR,t=13.37,P<0.05;HPTA+IR vs.IR,t=8.48,P<0.05).Immunofluorescence and immunoblotting experiments demonstrated that the VPA/HPTA+IR group displayed signifi-cantly increased cell foci formation,γH2AX and 53BP1 protein expression levels compared to the IR group[(γH2AX:VPA+IR vs.IR,t=8.88,P<0.05;HPTA+IR vs.IR,t=8.90,P<0.05),(53BP1,VPA+IR vs.IR,t=5.73,P<0.05;HPTA+IR vs.IR,t=6.40,P<0.05)].Further,Rad51 expression was downregulated(VPA+IR vs.IR,t=3.12,P<0.05;HPTA+IR vs.IR,t=2.70,P<0.05),and Rad51 inhibition effectively counteracted HPTA-induced radiosensitization.Ubiquitination detection further verified that HPTA inhibits Rad51 expression via UCHL3-dependent Rad51 deubiquitination.In vivo study results showed that 20 mg/kg HPTA significantly enhanced the radiosensitivity of breast tumors in rats by inhibiting Rad51 expression.Conclusions:HPTA is a highly effective radiosensitizer that enhances the radiotherapeutic efficacy of breast cancer treatment through UCHL3-dependent deubiquitination of Rad51.展开更多
基金supported by the National Natural Science Foundation of China(62103411)the Science and Technology Development Fund of Macao SAR(0093/2023/RIA2,0050/2020/A1)。
文摘The attention is a scarce resource in decentralized autonomous organizations(DAOs),as their self-governance relies heavily on the attention-intensive decision-making process of“proposal and voting”.To prevent the negative effects of pro-posers’attention-capturing strategies that contribute to the“tragedy of the commons”and ensure an efficient distribution of attention among multiple proposals,it is necessary to establish a market-driven allocation scheme for DAOs’attention.First,the Harberger tax-based attention markets are designed to facilitate its allocation via continuous and automated trading,where the individualized Harberger tax rate(HTR)determined by the pro-posers’reputation is adopted.Then,the Stackelberg game model is formulated in these markets,casting attention to owners in the role of leaders and other competitive proposers as followers.Its equilibrium trading strategies are also discussed to unravel the intricate dynamics of attention pricing.Moreover,utilizing the single-round Stackelberg game as an illustrative example,the existence of Nash equilibrium trading strategies is demonstrated.Finally,the impact of individualized HTR on trading strategies is investigated,and results suggest that it has a negative correlation with leaders’self-accessed prices and ownership duration,but its effect on their revenues varies under different conditions.This study is expected to provide valuable insights into leveraging attention resources to improve DAOs’governance and decision-making process.
基金This work was supported by the National Key Research and Development Program of China(2020YFB2104001)the National Natural Science Foundation of China(62271485,61903363,U1811463)Open Project of the State Key Laboratory for Management and Control of Complex Systems(20220117).
文摘From AlphaGo to ChatGPT,the field of AI has launched a series of remarkable achievements in recent years.Analyzing,comparing,and summarizing these achievements at the paradigm level is important for future AI innovation,but has not received sufficient attention.In this paper,we give an overview and perspective on machine learning paradigms.First,we propose a paradigm taxonomy with three levels and seven dimensions from a knowledge perspective.Accordingly,we give an overview on three basic and twelve extended learning paradigms,such as Ensemble Learning,Transfer Learning,etc.,with figures in unified style.We further analyze three advanced paradigms,i.e.,AlphaGo,AlphaFold and ChatGPT.Second,to enable more efficient and effective scientific discovery,we propose to build a new ecosystem that drives AI paradigm shifts through the decentralized science(DeSci)movement based on decentralized autonomous organization(DAO).To this end,we design the Hanoi framework,which integrates human factors,parallel intelligence based on a combination of artificial systems and the natural world,and the DAO to inspire AI innovations.
基金supported by grants from Zhejiang Provincial Natural Science Foundation of China(LQ23H14003)National Natural Science Foundation of China(81472800,82173460)+1 种基金Department of Science and Technology of Shandong Province(2019GSF108083)Zhejiang Provincial Postdoctoral Scientific Research Project Funding(ZJ2022076),China.
文摘Objective:To investigate the effects and underlying mechanism of 2-hexyl-4-pentynoic acid(HPTA),a derivative of valproic acid(VPA),on radiotherapy in breast cancer.Methods:MCF7 cells and 7,12-dimethylbenz-[α]-anthracene(DMBA)-induced transformed human normal breast cells(MCF10A–DMBA cells)were irradiated with 8 Gy X-rays.For both cells there were four groups:control,valproic acid(VPA)/HPTA,IR,and VPA/HPTA+IR groups.MTT and clonogenic survival assays were performed to assess cell proliferation,and comet assay was performed to evaluate DNA damage.Protein expression ofγH2AX,53BP1,Rad51,and BRCA1 was examined via immunofluorescence and immunoblotting.Cycloheximide chase and ubiquitination experiments were conducted to determine Rad51 ubiquitination.In vivo experiments involved a rat model of DMBA-induced breast cancer,with four fractionated doses of 2 Gy.Tumor tissue pathological changes andγH2AX,Rad51,and UCHL3 expression levels were measured by hematoxylin-eosin staining,immunohistochemistry,and immunoblotting.Results:Compared with the IR group,15μmol/L HPTA reduced the cell proliferation ability of irradiated MCF7 cells(t=2.16,P<0.05).The VPA/HPTA+IR group exhibited significantly increased DNA double-strand breaks relative to those in the IR group(VPA+IR vs.IR,t=13.37,P<0.05;HPTA+IR vs.IR,t=8.48,P<0.05).Immunofluorescence and immunoblotting experiments demonstrated that the VPA/HPTA+IR group displayed signifi-cantly increased cell foci formation,γH2AX and 53BP1 protein expression levels compared to the IR group[(γH2AX:VPA+IR vs.IR,t=8.88,P<0.05;HPTA+IR vs.IR,t=8.90,P<0.05),(53BP1,VPA+IR vs.IR,t=5.73,P<0.05;HPTA+IR vs.IR,t=6.40,P<0.05)].Further,Rad51 expression was downregulated(VPA+IR vs.IR,t=3.12,P<0.05;HPTA+IR vs.IR,t=2.70,P<0.05),and Rad51 inhibition effectively counteracted HPTA-induced radiosensitization.Ubiquitination detection further verified that HPTA inhibits Rad51 expression via UCHL3-dependent Rad51 deubiquitination.In vivo study results showed that 20 mg/kg HPTA significantly enhanced the radiosensitivity of breast tumors in rats by inhibiting Rad51 expression.Conclusions:HPTA is a highly effective radiosensitizer that enhances the radiotherapeutic efficacy of breast cancer treatment through UCHL3-dependent deubiquitination of Rad51.