通过优化汽轮机叶片的安装顺序,来减少安装后的残余不平衡量。对此提出一种阈值式迭代局部搜索(threshold iterative local search,TILS)算法,该算法在迭代局部搜索(iterative local search,ILS)算法基础上,采用阈值限定扰动与随机扰动...通过优化汽轮机叶片的安装顺序,来减少安装后的残余不平衡量。对此提出一种阈值式迭代局部搜索(threshold iterative local search,TILS)算法,该算法在迭代局部搜索(iterative local search,ILS)算法基础上,采用阈值限定扰动与随机扰动相结合的方法来跳出局部最优解,减少了平均到达局部最优解所需的迭代步数。实验证明,该方法可以在短时间内找到一个近似最优叶片排序组合,相对于ILS算法,搜索效率提高了20%以上。计算得到的合成质径积的近似最优解,相对于现有分组排序法、遗传算法、云自适应遗传算法(CAGA)等方法,分别减小到其最优解的0.33%~31%,且计算时间也大幅度减小。展开更多
Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore...Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore innovative approaches in T cell receptor(TCR)engineering and characterization to target the KRAS G12D7-16 mutation,providing potential strategies for overcoming this therapeutic challenge.Methods:In this innovative study,we engineered and characterized two T cell receptors(TCRs),KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation.These TCRs were isolated from tumor-infiltrating lymphocytes(TILs)derived from tumor tissues of patients with the KRAS G12D mutation.We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines.Results:KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope,significantly inducing IFN-γrelease and eliminating tumor cells without cross-reactivity or alloreactivity.Conclusions:The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation,showing potential for significant advancements in cancer immunotherapy.展开更多
文摘通过优化汽轮机叶片的安装顺序,来减少安装后的残余不平衡量。对此提出一种阈值式迭代局部搜索(threshold iterative local search,TILS)算法,该算法在迭代局部搜索(iterative local search,ILS)算法基础上,采用阈值限定扰动与随机扰动相结合的方法来跳出局部最优解,减少了平均到达局部最优解所需的迭代步数。实验证明,该方法可以在短时间内找到一个近似最优叶片排序组合,相对于ILS算法,搜索效率提高了20%以上。计算得到的合成质径积的近似最优解,相对于现有分组排序法、遗传算法、云自适应遗传算法(CAGA)等方法,分别减小到其最优解的0.33%~31%,且计算时间也大幅度减小。
基金funded by the key R&D Project of Hubei Province(Social Development),China(2022BCA018)the Cooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province),China(2022KF16)to Kanghong Hu.
文摘Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore innovative approaches in T cell receptor(TCR)engineering and characterization to target the KRAS G12D7-16 mutation,providing potential strategies for overcoming this therapeutic challenge.Methods:In this innovative study,we engineered and characterized two T cell receptors(TCRs),KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation.These TCRs were isolated from tumor-infiltrating lymphocytes(TILs)derived from tumor tissues of patients with the KRAS G12D mutation.We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines.Results:KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope,significantly inducing IFN-γrelease and eliminating tumor cells without cross-reactivity or alloreactivity.Conclusions:The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation,showing potential for significant advancements in cancer immunotherapy.
