BACKGROUND Although chronic-phase chronic myeloid leukemia(CP-CML)is treatable and nearly curable in about 50%of patients,accelerated-phase chronic myeloid leukemia(AP-CML)shows concerning drug resistance,while blast ...BACKGROUND Although chronic-phase chronic myeloid leukemia(CP-CML)is treatable and nearly curable in about 50%of patients,accelerated-phase chronic myeloid leukemia(AP-CML)shows concerning drug resistance,while blast crisis chronic myeloid leukemia(BC-CML)is highly lethal.Advances in whole exome sequencing(WES)reveal pan-cancer mutations in BC-CML,supporting mutation-guided therapies beyond Breakpoint cluster region-Abelson.Artificial intelligence(AI)and machine learning(ML)enable genomic stratification and drug repurposing,addressing overlooked actionable mutations.AIM To stratify BC-CML into molecular subtypes using WES,ML,and AI for precision drug repurposing.METHODS Included 123 CML patients(111 CP-CML,5 AP-CML,7 BC-CML).WES identified pan-cancer mutations.Variants annotated via Ensembl Variant Effect Predictor and Catalogue of Somatic Mutations in Cancer(COSMIC).ML(principal component analysis,K-means)stratified BC-CML.COSMIC signatures and PanDrugs prioritized drugs.Analysis of variance/Kruskal-Wallis validated differences(P<0.05).RESULTS In this exploratory,hypothesis-generating study of BC-CML patients(n=7),we detected over 2500 somatic mutations.ML identified three BC-CML clusters:(1)Cluster 1[breast cancer susceptibility gene 2(BRCA2),TP53];(2)Cluster 2[isocitrate dehydrogenase(IDH)1/2,ten-eleven translocation 2];and(3)Cluster 3[Janus kinase(JAK)2,colony-stimulating factor 3 receptor],with distinct COSMIC signatures.Therapies:(1)Polyadenosinediphosphate-ribose polymerase inhibitors(olaparib);(2)IDH inhibitors(ivosidenib);and(3)JAK inhibitors(ruxolitinib).Mutational burden,signatures,and targets varied significantly across clusters,supporting precision stratification.CONCLUSION This WES-AI-ML framework provides mutation-guided therapies for BC-CML,enabling real-time stratification and Food and Drug Administration-approved drug repurposing.While this exploratory study is limited by its small sample size(n=7),it establishes a methodological framework for precision oncology stratification that warrants validation in larger,multi-center cohorts.展开更多
The key technologies of precision blasting were put forward based on the characteristics of urban via- duct blasting demolition in complicated surroundings. Initial bending instability mechanics model of reinforcing s...The key technologies of precision blasting were put forward based on the characteristics of urban via- duct blasting demolition in complicated surroundings. Initial bending instability mechanics model of reinforcing steel bar frame of blasting fragmented pier and sequenced collapsed dynamic model were established for quanti- tative blasting design. Technologies of water pressure blasting were applied in multi-cell box girder fragmenta- tion. The detonating network of non-electric duplication crossover was adopted for the safety and reliability of ultra-long delay. The rationality of blasting scheme and parameters were validated by physical model test. Harm- ful effects were forecasted and controlled by integrated protective technologies. Specialization, cooperation, pre- cision, execution （SCPE） project management method was put forward for precision management. The key tech- nologies of precision demolition blasting can provide reference for similar proiects.展开更多
To deal with the construction difficulties of Xiangjiaba underground hydropower station,such as complex geological conditions,narrow rock bench,high loading,high quality requirements and urgent time limit,the project ...To deal with the construction difficulties of Xiangjiaba underground hydropower station,such as complex geological conditions,narrow rock bench,high loading,high quality requirements and urgent time limit,the project adopted the concept of precision blasting.The explosive energy and rock mass fragmentation were well controlled by taking reasonable excavation sequence,designing steel pipe drilling frame,the additional techniques of double layer smooth blasting,evenly micro charge,staggered arrangement of boreholes and pre-stressed anchors.These technologies ensured the excavation quality of the rock face beam,achieving successful blasting results:Semi hole ratio was 100%in Ⅱ surrounding rock,99.2%in Ⅲ surrounding rock and 90%~ 97.3%in Ⅳ surrounding rock;underbreak was avoided and the average backbreak was only2.9 cm;the unevenness was 0 ~ 4 cm;the influence depth of blasting and unloading was 0.2 ~ 0.7 cm.展开更多
Precision blasting,which is different from traditional control blasting,is regarded as the sign of new development stage of engineering blasting.The definition,connotation,technology system and current situation of it...Precision blasting,which is different from traditional control blasting,is regarded as the sign of new development stage of engineering blasting.The definition,connotation,technology system and current situation of its application and development were described briefly.With regard to the prospect of precision blasting,following aspects for further study are recommended:a.A multiple disciplinary study should be developed for a more understanding on the explosive energy release and quantitative blasting design;b.according to the requirements of digital blasting objective,syncretic study of precision blasting and technology should be enhanced;c.numerical simulation was an important tool for optimizing engineering blasting scheme and blasting harmful effects control,a more elaborate precision numerical simulation method should be studied furthermore;d.the modernization and standardization of precision blasting construction should be enhanced.展开更多
文摘BACKGROUND Although chronic-phase chronic myeloid leukemia(CP-CML)is treatable and nearly curable in about 50%of patients,accelerated-phase chronic myeloid leukemia(AP-CML)shows concerning drug resistance,while blast crisis chronic myeloid leukemia(BC-CML)is highly lethal.Advances in whole exome sequencing(WES)reveal pan-cancer mutations in BC-CML,supporting mutation-guided therapies beyond Breakpoint cluster region-Abelson.Artificial intelligence(AI)and machine learning(ML)enable genomic stratification and drug repurposing,addressing overlooked actionable mutations.AIM To stratify BC-CML into molecular subtypes using WES,ML,and AI for precision drug repurposing.METHODS Included 123 CML patients(111 CP-CML,5 AP-CML,7 BC-CML).WES identified pan-cancer mutations.Variants annotated via Ensembl Variant Effect Predictor and Catalogue of Somatic Mutations in Cancer(COSMIC).ML(principal component analysis,K-means)stratified BC-CML.COSMIC signatures and PanDrugs prioritized drugs.Analysis of variance/Kruskal-Wallis validated differences(P<0.05).RESULTS In this exploratory,hypothesis-generating study of BC-CML patients(n=7),we detected over 2500 somatic mutations.ML identified three BC-CML clusters:(1)Cluster 1[breast cancer susceptibility gene 2(BRCA2),TP53];(2)Cluster 2[isocitrate dehydrogenase(IDH)1/2,ten-eleven translocation 2];and(3)Cluster 3[Janus kinase(JAK)2,colony-stimulating factor 3 receptor],with distinct COSMIC signatures.Therapies:(1)Polyadenosinediphosphate-ribose polymerase inhibitors(olaparib);(2)IDH inhibitors(ivosidenib);and(3)JAK inhibitors(ruxolitinib).Mutational burden,signatures,and targets varied significantly across clusters,supporting precision stratification.CONCLUSION This WES-AI-ML framework provides mutation-guided therapies for BC-CML,enabling real-time stratification and Food and Drug Administration-approved drug repurposing.While this exploratory study is limited by its small sample size(n=7),it establishes a methodological framework for precision oncology stratification that warrants validation in larger,multi-center cohorts.
文摘The key technologies of precision blasting were put forward based on the characteristics of urban via- duct blasting demolition in complicated surroundings. Initial bending instability mechanics model of reinforcing steel bar frame of blasting fragmented pier and sequenced collapsed dynamic model were established for quanti- tative blasting design. Technologies of water pressure blasting were applied in multi-cell box girder fragmenta- tion. The detonating network of non-electric duplication crossover was adopted for the safety and reliability of ultra-long delay. The rationality of blasting scheme and parameters were validated by physical model test. Harm- ful effects were forecasted and controlled by integrated protective technologies. Specialization, cooperation, pre- cision, execution （SCPE） project management method was put forward for precision management. The key tech- nologies of precision demolition blasting can provide reference for similar proiects.
文摘To deal with the construction difficulties of Xiangjiaba underground hydropower station,such as complex geological conditions,narrow rock bench,high loading,high quality requirements and urgent time limit,the project adopted the concept of precision blasting.The explosive energy and rock mass fragmentation were well controlled by taking reasonable excavation sequence,designing steel pipe drilling frame,the additional techniques of double layer smooth blasting,evenly micro charge,staggered arrangement of boreholes and pre-stressed anchors.These technologies ensured the excavation quality of the rock face beam,achieving successful blasting results:Semi hole ratio was 100%in Ⅱ surrounding rock,99.2%in Ⅲ surrounding rock and 90%~ 97.3%in Ⅳ surrounding rock;underbreak was avoided and the average backbreak was only2.9 cm;the unevenness was 0 ~ 4 cm;the influence depth of blasting and unloading was 0.2 ~ 0.7 cm.
文摘Precision blasting,which is different from traditional control blasting,is regarded as the sign of new development stage of engineering blasting.The definition,connotation,technology system and current situation of its application and development were described briefly.With regard to the prospect of precision blasting,following aspects for further study are recommended:a.A multiple disciplinary study should be developed for a more understanding on the explosive energy release and quantitative blasting design;b.according to the requirements of digital blasting objective,syncretic study of precision blasting and technology should be enhanced;c.numerical simulation was an important tool for optimizing engineering blasting scheme and blasting harmful effects control,a more elaborate precision numerical simulation method should be studied furthermore;d.the modernization and standardization of precision blasting construction should be enhanced.
