Fault-tolerance is very important in cluster computing and has beenimplemented in many famous cluster-computing systems using checkpoint/restartmechanisms. But existent check-pointing algorithms cannot restore the sta...Fault-tolerance is very important in cluster computing and has beenimplemented in many famous cluster-computing systems using checkpoint/restartmechanisms. But existent check-pointing algorithms cannot restore the states of afile system when roll-backing the running of a program, so there are many restrictionson file accesses in existent fault-tolerance systems. SCR algorithm, an algorithmbased on atomic operation and consistent schedule, which can restore the states offile systems, is presented in this paper. In the SCR algorithm, system calls on filesystems are classified into idem-potent operations and non-idem-potent operations.A non-idem-potent operation modifies a file system's states, while an idem-potentoperation does not. SCR algorithm tracks changes of the file system states. It logseach non-idem-potent operation used by user programs and the information that canrestore the operation in disks. When check-pointing roll-backing the program, SCRalgorithm will revert the file system states to the last checkpoint time. By usingSCR algorithm, users are allowed to use any file operation in their programs.展开更多
Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollbac...Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.展开更多
Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in Februa...Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.展开更多
目的:探讨si RNA沉默检测点激酶1(Chk1)基因对人卵巢癌细胞HO8910增殖和周期调控的影响及其作用机制。方法:设计并合成3条Chk1 si RNA干扰片段,转染进入卵巢癌细胞HO8910,Western blot检测转染前后HO8910细胞中Chk1蛋白的表达情况,筛选...目的:探讨si RNA沉默检测点激酶1(Chk1)基因对人卵巢癌细胞HO8910增殖和周期调控的影响及其作用机制。方法:设计并合成3条Chk1 si RNA干扰片段,转染进入卵巢癌细胞HO8910,Western blot检测转染前后HO8910细胞中Chk1蛋白的表达情况,筛选出有效片段。将Chk1 si RNA有效片段转染进入HO8910细胞,采用MTT法和流式细胞仪分析Chk1si RNA对HO8910细胞增殖和周期的影响;Western blot方法分别检测细胞周期相关基因Cyclin A、CDK4、Cdc25A蛋白表达。结果:3个si RNA中,1条是有效si RNA。该有效Chk1 si RNA片段转染后,HO8910细胞中Chk1蛋白水平下降约53.6%,明显低于未转染组和脂质体转染组(P=0.000)。转染48 h后,Chk1 si RNA转染组HO8910细胞增殖活性下降,抑制率为(52.1±5.1)%,明显高于脂质体转染组的(7.6±3.8)%(P=0.000)。流式细胞仪检测显示Chk1 si RNA转染组HO8910细胞G2/M期比例为(5.03±2.62)%,明显低于未转染组(19.35±2.19)%和脂质体转染组(19.76±2.67)%(P=0.000)。Western blot结果显示转染Chk1 si RNA后,细胞内与细胞周期相关的Cyclin A、CDK4、Cdc25A蛋白水平表达明显增强,与未转染组和脂质体组比较,差异有统计学意义(P=0.000)。结论:si RNA沉默Chk1基因后,可明显抑制卵巢癌细胞HO8910细胞的增殖,其抑制增殖作用与减弱G2/M期阻滞有关。展开更多
文摘Fault-tolerance is very important in cluster computing and has beenimplemented in many famous cluster-computing systems using checkpoint/restartmechanisms. But existent check-pointing algorithms cannot restore the states of afile system when roll-backing the running of a program, so there are many restrictionson file accesses in existent fault-tolerance systems. SCR algorithm, an algorithmbased on atomic operation and consistent schedule, which can restore the states offile systems, is presented in this paper. In the SCR algorithm, system calls on filesystems are classified into idem-potent operations and non-idem-potent operations.A non-idem-potent operation modifies a file system's states, while an idem-potentoperation does not. SCR algorithm tracks changes of the file system states. It logseach non-idem-potent operation used by user programs and the information that canrestore the operation in disks. When check-pointing roll-backing the program, SCRalgorithm will revert the file system states to the last checkpoint time. By usingSCR algorithm, users are allowed to use any file operation in their programs.
基金Project supported by the National "863" High-tech Program of China.
文摘Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.
文摘Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.
文摘目的:探讨si RNA沉默检测点激酶1(Chk1)基因对人卵巢癌细胞HO8910增殖和周期调控的影响及其作用机制。方法:设计并合成3条Chk1 si RNA干扰片段,转染进入卵巢癌细胞HO8910,Western blot检测转染前后HO8910细胞中Chk1蛋白的表达情况,筛选出有效片段。将Chk1 si RNA有效片段转染进入HO8910细胞,采用MTT法和流式细胞仪分析Chk1si RNA对HO8910细胞增殖和周期的影响;Western blot方法分别检测细胞周期相关基因Cyclin A、CDK4、Cdc25A蛋白表达。结果:3个si RNA中,1条是有效si RNA。该有效Chk1 si RNA片段转染后,HO8910细胞中Chk1蛋白水平下降约53.6%,明显低于未转染组和脂质体转染组(P=0.000)。转染48 h后,Chk1 si RNA转染组HO8910细胞增殖活性下降,抑制率为(52.1±5.1)%,明显高于脂质体转染组的(7.6±3.8)%(P=0.000)。流式细胞仪检测显示Chk1 si RNA转染组HO8910细胞G2/M期比例为(5.03±2.62)%,明显低于未转染组(19.35±2.19)%和脂质体转染组(19.76±2.67)%(P=0.000)。Western blot结果显示转染Chk1 si RNA后,细胞内与细胞周期相关的Cyclin A、CDK4、Cdc25A蛋白水平表达明显增强,与未转染组和脂质体组比较,差异有统计学意义(P=0.000)。结论:si RNA沉默Chk1基因后,可明显抑制卵巢癌细胞HO8910细胞的增殖,其抑制增殖作用与减弱G2/M期阻滞有关。
