In wireless sensor networks, the missing of sensor data is inevitable due to the inherent characteristic of wireless sensor networks, and it causes many difficulties in various applications. To solve the problem, the ...In wireless sensor networks, the missing of sensor data is inevitable due to the inherent characteristic of wireless sensor networks, and it causes many difficulties in various applications. To solve the problem, the missing data should be estimated as accurately as possible. In this paper, a k-nearest neighbor based missing data estimation algorithm is proposed based on the temporal and spatial correlation of sensor data. It adopts the linear regression model to describe the spatial correlation of sensor data among different sensor nodes, and utilizes the data information of multiple neighbor nodes to estimate the missing data jointly rather than independently, so that a stable and reliable estimation performance can be achieved. Experimental results on two real-world datasets show that the proposed algorithm can estimate the missing data accurately.展开更多
Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor ...Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.展开更多
Dear Editor,The epidermal growth factor receptor(EGFR),one member of the ErbB family of receptor tyrosine kinases,has been implicated in various epithelial malignancies.As a clinically validated target,both small-mole...Dear Editor,The epidermal growth factor receptor(EGFR),one member of the ErbB family of receptor tyrosine kinases,has been implicated in various epithelial malignancies.As a clinically validated target,both small-molecule tyrosine kinase inhibitors and antibody-based drugs have been approved by regulatory agencies.Anti-EGFR antibodyci rug conjugates(ADCs)could kill target tumor cells irrespective of EGFR signaling.However,cancer patients treated with EGFR-targeted antibody therapy eventually develop acquired epitope substitutions such as S492R,G465R,G465E,and 1491M.展开更多
Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells.The successful application of I...Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells.The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies,such as antibody fragments,bispecific antibodies,and antibody derivatives(e.g.,antibody-drug conjugates and immunocytokines).展开更多
文摘In wireless sensor networks, the missing of sensor data is inevitable due to the inherent characteristic of wireless sensor networks, and it causes many difficulties in various applications. To solve the problem, the missing data should be estimated as accurately as possible. In this paper, a k-nearest neighbor based missing data estimation algorithm is proposed based on the temporal and spatial correlation of sensor data. It adopts the linear regression model to describe the spatial correlation of sensor data among different sensor nodes, and utilizes the data information of multiple neighbor nodes to estimate the missing data jointly rather than independently, so that a stable and reliable estimation performance can be achieved. Experimental results on two real-world datasets show that the proposed algorithm can estimate the missing data accurately.
基金supported by the National Key Research and Development Program of China‘Precision Medicine Research’(Grant No.2017YFC0908602)the State Key Program of National Natural Science of China(Grant No.81430081)National Key R&D Program of China(No.2017YFE0102200)。
文摘Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.
基金supported by the National Natural Science Foundation of China(Grant No.82073750)National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(2017ZX09302006002)+3 种基金Key research and development project of Zhejiang Province(No.2O18CO3O22)National Key R&D Program of China(No.2017YFE0102200)the Fundamental Research Funds for the Central Universities(No.2020QNA7005)Zhejiang Province"Qianjiang Talent Plan".
文摘Dear Editor,The epidermal growth factor receptor(EGFR),one member of the ErbB family of receptor tyrosine kinases,has been implicated in various epithelial malignancies.As a clinically validated target,both small-molecule tyrosine kinase inhibitors and antibody-based drugs have been approved by regulatory agencies.Anti-EGFR antibodyci rug conjugates(ADCs)could kill target tumor cells irrespective of EGFR signaling.However,cancer patients treated with EGFR-targeted antibody therapy eventually develop acquired epitope substitutions such as S492R,G465R,G465E,and 1491M.
基金This study was supported by Joint Funds of the National Natural Science Foundation of China(Grant No.U20A20409)National Natural Science Foundation of China(Grant No.82073750)+2 种基金Key research and development project of Zhejiang province(No.2018C03022)the Fundamental Research Funds for the Central Universities(No.2020QNA7005)Zhejiang Province"Qianjiang Talent Plan".
文摘Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells.The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies,such as antibody fragments,bispecific antibodies,and antibody derivatives(e.g.,antibody-drug conjugates and immunocytokines).