Sapacitabine is an orally bioavailable prodrug of the nucleoside analog 2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine(CNDAC).Both the prodrug and active metabolite are in clinical trials for hemato...Sapacitabine is an orally bioavailable prodrug of the nucleoside analog 2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine(CNDAC).Both the prodrug and active metabolite are in clinical trials for hematologic malignancies and/or solid tumors.CNDAC has a unique mechanism of action:after incorporation into DNA,it induces single-strand breaks(SSBs) that are converted into double-strand breaks(DSBs) when cells go through a second S phase.In our previous studies,we demonstrated that CNDAC-induced SSBs can be repaired by the transcription-coupled nucleotide excision repair pathway,whereas lethal DSBs are mainly repaired through homologous recombination.In the current work,we used clonogenic assays to compare the DNA damage repair mechanism of CNDAC with two other deoxycytidine analogs:cytarabine,which is used in hematologic malignacies,and gemcitabine,which shows activity in solid tumors.Deficiency in two Rad51 paralogs,Rad51D and XRCC3,greatly sensitized cells to CNDAC,but not to cytarabine or gemcitabine,indicating that homologous recombination is not a major mechanism for repairing damage caused by the latter two analogs.This study further suggests clinical activity and application of sapacitabine that is distinct from that of cytarabine or gemcitabine.展开更多
Ultraviolet（UV） radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. O...Ultraviolet（UV） radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. One contains hourly observations of UV radiation measured at 40 Chinese Ecosystem Research Network stations from 2005 to 2015. CUV3 broadband radiometers were used to observe the UV radiation, with an accuracy of 5%, which meets the World Meteorology Organization＇s measurement standards. The extremum method was used to control the quality of the measured datasets. The other dataset contains daily cumulative UV radiation estimates that were calculated using an all-sky estimation model combined with a hybrid model. The reconstructed daily UV radiation data span from 1961 to 2014. The mean absolute bias error and root-mean-square error are smaller than 30% at most stations, and most of the mean bias error values are negative, which indicates underestimation of the UV radiation intensity. These datasets can improve our basic knowledge of the spatial and temporal variations in UV radiation. Additionally, these datasets can be used in studies of potential ozone formation and atmospheric oxidation, as well as simulations of ecological processes.展开更多
基金supported by grants from the National Cancer Institute,Department of Health and Human Services,USA(CA28596,CA81534 and CA100632)
文摘Sapacitabine is an orally bioavailable prodrug of the nucleoside analog 2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine(CNDAC).Both the prodrug and active metabolite are in clinical trials for hematologic malignancies and/or solid tumors.CNDAC has a unique mechanism of action:after incorporation into DNA,it induces single-strand breaks(SSBs) that are converted into double-strand breaks(DSBs) when cells go through a second S phase.In our previous studies,we demonstrated that CNDAC-induced SSBs can be repaired by the transcription-coupled nucleotide excision repair pathway,whereas lethal DSBs are mainly repaired through homologous recombination.In the current work,we used clonogenic assays to compare the DNA damage repair mechanism of CNDAC with two other deoxycytidine analogs:cytarabine,which is used in hematologic malignacies,and gemcitabine,which shows activity in solid tumors.Deficiency in two Rad51 paralogs,Rad51D and XRCC3,greatly sensitized cells to CNDAC,but not to cytarabine or gemcitabine,indicating that homologous recombination is not a major mechanism for repairing damage caused by the latter two analogs.This study further suggests clinical activity and application of sapacitabine that is distinct from that of cytarabine or gemcitabine.
文摘Ultraviolet（UV） radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. One contains hourly observations of UV radiation measured at 40 Chinese Ecosystem Research Network stations from 2005 to 2015. CUV3 broadband radiometers were used to observe the UV radiation, with an accuracy of 5%, which meets the World Meteorology Organization＇s measurement standards. The extremum method was used to control the quality of the measured datasets. The other dataset contains daily cumulative UV radiation estimates that were calculated using an all-sky estimation model combined with a hybrid model. The reconstructed daily UV radiation data span from 1961 to 2014. The mean absolute bias error and root-mean-square error are smaller than 30% at most stations, and most of the mean bias error values are negative, which indicates underestimation of the UV radiation intensity. These datasets can improve our basic knowledge of the spatial and temporal variations in UV radiation. Additionally, these datasets can be used in studies of potential ozone formation and atmospheric oxidation, as well as simulations of ecological processes.
