Combined cycle plants (CCs) are broadly used all over the world. The inclusion of CCs into the optimal resource scheduling causes difficulties because they can be operated in different operating configuration modes ba...Combined cycle plants (CCs) are broadly used all over the world. The inclusion of CCs into the optimal resource scheduling causes difficulties because they can be operated in different operating configuration modes based on the number of combustion and steam turbines. In this paper a model CCs based on a mixed integer linear programming approach to be included into an optimal short term resource optimization problem is presented. The proposed method allows modeling of CCs in different modes of operation taking into account the non convex operating costs for the different combined cycle mode of operation.展开更多
Task scheduling for electro-magnetic detection satellite is a typical combinatorial optimization problem. The count of constraints that need to be taken into account is of large scale. An algorithm combined integer pr...Task scheduling for electro-magnetic detection satellite is a typical combinatorial optimization problem. The count of constraints that need to be taken into account is of large scale. An algorithm combined integer programming with constraint programming is presented. This algorithm is deployed in this problem through two steps. The first step is to decompose the original problem into master and sub-problem using the logic-based Benders decomposition; then a circus combines master and sub-problem solving process together, and the connection between them is general Benders cut. This hybrid algorithm is tested by a set of derived experiments. The result is compared with corresponding outcomes generated by the strength Pareto evolutionary algorithm and the pure constraint programming solver GECODE, which is an open source software. These tests and comparisons yield promising effect.展开更多
BACKGROUND Immunotherapy targeting programmed death-1(PD-1)or programmed deathligand-1(PD-L1)has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma(PDAC)....BACKGROUND Immunotherapy targeting programmed death-1(PD-1)or programmed deathligand-1(PD-L1)has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma(PDAC).Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy.Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes.Protein arginine methylation is a common posttranslational modification.Protein arginine methyltransferase(PRMT)1 is deregulated in a wide variety of cancer types,whose biological role in tumor immunity is undefined.AIM To investigate the combined effects and underlying mechanisms of anti-PD-L1 and type I PRMT inhibitor in pancreatic cancer in vivo.METHODS PT1001B is a novel type I PRMT inhibitor with strong activity and good selectivity.A mouse model of subcutaneous Panc02-derived tumors was used to evaluate drug efficacy,toxic and side effects,and tumor growth in vivo.By flow cytometry,we determined the expression of key immune checkpoint proteins,detected the apoptosis in tumor tissues,and analyzed the immune cells.Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67,TUNEL assay,and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect.RESULTS Cultured Panc02 cells did not express PD-L1 in vitro,but tumor cells derived from Panc02 transplanted tumors expressed PD-L1.The therapeutic efficacy of anti-PD-L1 mAb was significantly enhanced by the addition of PT1001B as measured by tumor volume(1054.00±61.37 mm3 vs 555.80±74.42 mm3,P<0.01)and tumor weight(0.83±0.06 g vs 0.38±0.02 g,P<0.05).PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells(32.74%±5.89%vs 17.95%±1.92%,P<0.05).The combination therapy upregulated tumorinfiltrating CD8+T lymphocytes(23.75%±3.20%vs 73.34%±4.35%,P<0.01)and decreased PD-1+leukocytes(35.77%±3.30%vs 6.48%±1.08%,P<0.001)in tumor tissue compared to the control.In addition,PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis.PRMT1 downregulation was correlated with PD-L1 downregulation.CONCLUSION PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.展开更多
We studied the feedback maximization of reliability of multi-degree-of-freedom （MDOF） quasi integrable-Hamiltonian systems under combined harmonic and white noise excitations. First, the partially averaged Ito equat...We studied the feedback maximization of reliability of multi-degree-of-freedom （MDOF） quasi integrable-Hamiltonian systems under combined harmonic and white noise excitations. First, the partially averaged Ito equations are derived by using the stochastic averaging method for quasi integrable-Hamiltonian systems under combined harmonic and white noise excitations. Then, the dynamical programming equation and its boundary and final time conditions for the control problems of maximizing the reliability is established from the partially averaged equations by using the dynamical programming principle. The nonlinear stochastic optimal control for maximizing the reliability is determined from the dynamical programming equation and control constrains. The reliability function of optimally controlled systems is obtained by solving the final dynamical programming equation. Finally, the application of the proposed procedure and effectiveness of the control strategy are illustrated by using an example.展开更多
In order to increase the convenience of application and minimize logistical problems in the recent years, the use of combined vaccines has become a growing trend. The use of combined vaccines offers benefits such as, ...In order to increase the convenience of application and minimize logistical problems in the recent years, the use of combined vaccines has become a growing trend. The use of combined vaccines offers benefits such as, a reduction in the number of patient visits, less complications which are associated with multiple intramuscular drilling and other risks. In 1997 the Department of Epidemiology （DE） of Institute of Public Health initiated and carried out conspicuous quantitative and qualitative modifications of up-to-them statutory notification system thus compiling the new Major Disease-Based Epidemiological Surveillance System. Mandatory reporting system on Measles/Rubella Case-Based Surveillance represents in itself an addendum of the statutory reporting system of infectious diseases. These diseases are enlisted in the Group B of the 14/Sh Form. Diphtheria is enlisted in the Group A containing the infectious diseases of the highest public health importance. They are subject of a mandatory urgent notification from the basic level. The aim of this study is to examine and check up the effectiveness of combined vaccines in our country, through the evaluation of the data from national epidemiologic surveillance verifying the distributions in time and space of these diseases in relation to the history of vaccination policies in Albania.展开更多
This article, in order to guarantee the stable mode transition in tandem turbo-ramjet engines, investigates the multi-objective and multi-variable goal programming algorithm. First, it introduces the structural featur...This article, in order to guarantee the stable mode transition in tandem turbo-ramjet engines, investigates the multi-objective and multi-variable goal programming algorithm. First, it introduces the structural features of the variable cycle turbo-ramjet engines, the principles of selecting the mode transition operation point and the design parameters, and the characteristics of the turbofan mode and the ramjet mode. Second, a component-based variable cycle turbo-ramjet engine model is developed to simulate the mode transition process. Third, the Newton-Raphson algorithm is used to solve the multi-variable and multi-objective optimization problem. The results show that with the maximum residua of only 0.06%, this algorithm has an acceptable convergence that meets the predetermined goals. Finally, the simulation shows that the stable turbo-ramjet mode transition could be realized with the mode transition control law developed by the algorithm.展开更多
BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibito...BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.展开更多
A new kind of combining forecasting model based on the generalized weighted functional proportional mean is proposed and the parameter estimation method of its weighting coefficients by means of the algorithm of quadr...A new kind of combining forecasting model based on the generalized weighted functional proportional mean is proposed and the parameter estimation method of its weighting coefficients by means of the algorithm of quadratic programming is given. This model has extensive representation. It is a new kind of aggregative method of group forecasting. By taking the suitable combining form of the forecasting models and seeking the optimal parameter, the optimal combining form can be obtained and the forecasting accuracy can be improved. The effectiveness of this model is demonstrated by an example.展开更多
The autonomous route planning in coverage search is an important subject of unmanned aerial vehicle(UAV) mission planning. Pre-planning is simple and feasible for the coverage search mission of single UAV in regular a...The autonomous route planning in coverage search is an important subject of unmanned aerial vehicle(UAV) mission planning. Pre-planning is simple and feasible for the coverage search mission of single UAV in regular areas. As to the dynamic mission in complicated environment of multi-UAV, the route planning will encounter the difficulties of reasonable task distribution and the real-time environment changes which include the changes of the mission area, the detection of threat area, the interference of communication and so on. At this point, making the UAV to do real-time autonomous planning is necessary. However, it is hard to fulfil requirements of real-time, autonomous and efficient at the same time. According to a scalable knowledge base,this paper proposes a coverage search algorithm which is based on the mapping between the basic behavior combination and surroundings. A UAV's coverage search simulation model with random shapes is built with a discrete map to update the environment and the changes of the mission on time. Comparison of the simulation analysis and the dynamic programming shows that the method has amazing expandability and can change the search strategy feasibly. It is efficient, and the ratio of coverage redundancy can be decreased to 1.21. It also has the potentiality in real-time calculation, and the computing time can be shortened to about 2 s.展开更多
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies th...Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.展开更多
文摘Combined cycle plants (CCs) are broadly used all over the world. The inclusion of CCs into the optimal resource scheduling causes difficulties because they can be operated in different operating configuration modes based on the number of combustion and steam turbines. In this paper a model CCs based on a mixed integer linear programming approach to be included into an optimal short term resource optimization problem is presented. The proposed method allows modeling of CCs in different modes of operation taking into account the non convex operating costs for the different combined cycle mode of operation.
基金supported by the National Security Fundamental Research Foundation of China (61361)the National Natural Science Foundation of China (61104180)
文摘Task scheduling for electro-magnetic detection satellite is a typical combinatorial optimization problem. The count of constraints that need to be taken into account is of large scale. An algorithm combined integer programming with constraint programming is presented. This algorithm is deployed in this problem through two steps. The first step is to decompose the original problem into master and sub-problem using the logic-based Benders decomposition; then a circus combines master and sub-problem solving process together, and the connection between them is general Benders cut. This hybrid algorithm is tested by a set of derived experiments. The result is compared with corresponding outcomes generated by the strength Pareto evolutionary algorithm and the pure constraint programming solver GECODE, which is an open source software. These tests and comparisons yield promising effect.
基金Supported by the National Natural Science Foundation of China,No. 81472844
文摘BACKGROUND Immunotherapy targeting programmed death-1(PD-1)or programmed deathligand-1(PD-L1)has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma(PDAC).Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy.Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes.Protein arginine methylation is a common posttranslational modification.Protein arginine methyltransferase(PRMT)1 is deregulated in a wide variety of cancer types,whose biological role in tumor immunity is undefined.AIM To investigate the combined effects and underlying mechanisms of anti-PD-L1 and type I PRMT inhibitor in pancreatic cancer in vivo.METHODS PT1001B is a novel type I PRMT inhibitor with strong activity and good selectivity.A mouse model of subcutaneous Panc02-derived tumors was used to evaluate drug efficacy,toxic and side effects,and tumor growth in vivo.By flow cytometry,we determined the expression of key immune checkpoint proteins,detected the apoptosis in tumor tissues,and analyzed the immune cells.Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67,TUNEL assay,and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect.RESULTS Cultured Panc02 cells did not express PD-L1 in vitro,but tumor cells derived from Panc02 transplanted tumors expressed PD-L1.The therapeutic efficacy of anti-PD-L1 mAb was significantly enhanced by the addition of PT1001B as measured by tumor volume(1054.00±61.37 mm3 vs 555.80±74.42 mm3,P<0.01)and tumor weight(0.83±0.06 g vs 0.38±0.02 g,P<0.05).PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells(32.74%±5.89%vs 17.95%±1.92%,P<0.05).The combination therapy upregulated tumorinfiltrating CD8+T lymphocytes(23.75%±3.20%vs 73.34%±4.35%,P<0.01)and decreased PD-1+leukocytes(35.77%±3.30%vs 6.48%±1.08%,P<0.001)in tumor tissue compared to the control.In addition,PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis.PRMT1 downregulation was correlated with PD-L1 downregulation.CONCLUSION PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.
基金Project supported by the National Natural Science Foundation of China (No. 10772159)the Research Fund for the Doctoral Program of Higher Education of China (No. 20060335125)the Zhejiang Provincial Nature Science Foundation of China (No. Y7080070)
文摘We studied the feedback maximization of reliability of multi-degree-of-freedom （MDOF） quasi integrable-Hamiltonian systems under combined harmonic and white noise excitations. First, the partially averaged Ito equations are derived by using the stochastic averaging method for quasi integrable-Hamiltonian systems under combined harmonic and white noise excitations. Then, the dynamical programming equation and its boundary and final time conditions for the control problems of maximizing the reliability is established from the partially averaged equations by using the dynamical programming principle. The nonlinear stochastic optimal control for maximizing the reliability is determined from the dynamical programming equation and control constrains. The reliability function of optimally controlled systems is obtained by solving the final dynamical programming equation. Finally, the application of the proposed procedure and effectiveness of the control strategy are illustrated by using an example.
文摘In order to increase the convenience of application and minimize logistical problems in the recent years, the use of combined vaccines has become a growing trend. The use of combined vaccines offers benefits such as, a reduction in the number of patient visits, less complications which are associated with multiple intramuscular drilling and other risks. In 1997 the Department of Epidemiology （DE） of Institute of Public Health initiated and carried out conspicuous quantitative and qualitative modifications of up-to-them statutory notification system thus compiling the new Major Disease-Based Epidemiological Surveillance System. Mandatory reporting system on Measles/Rubella Case-Based Surveillance represents in itself an addendum of the statutory reporting system of infectious diseases. These diseases are enlisted in the Group B of the 14/Sh Form. Diphtheria is enlisted in the Group A containing the infectious diseases of the highest public health importance. They are subject of a mandatory urgent notification from the basic level. The aim of this study is to examine and check up the effectiveness of combined vaccines in our country, through the evaluation of the data from national epidemiologic surveillance verifying the distributions in time and space of these diseases in relation to the history of vaccination policies in Albania.
文摘This article, in order to guarantee the stable mode transition in tandem turbo-ramjet engines, investigates the multi-objective and multi-variable goal programming algorithm. First, it introduces the structural features of the variable cycle turbo-ramjet engines, the principles of selecting the mode transition operation point and the design parameters, and the characteristics of the turbofan mode and the ramjet mode. Second, a component-based variable cycle turbo-ramjet engine model is developed to simulate the mode transition process. Third, the Newton-Raphson algorithm is used to solve the multi-variable and multi-objective optimization problem. The results show that with the maximum residua of only 0.06%, this algorithm has an acceptable convergence that meets the predetermined goals. Finally, the simulation shows that the stable turbo-ramjet mode transition could be realized with the mode transition control law developed by the algorithm.
基金Supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,No.2021-I2M-1-061 and 2021-I2M-1-003Chinese Society of Clinical Oncology-Hengrui Cancer Research Fund,No.Y-HR2019-0239+1 种基金Chinese Society of Clinical Oncology-MSD Cancer Research Fund,No.Y-MSDZD2021-0213National Ten-thousand Talent Program.
文摘BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.
文摘A new kind of combining forecasting model based on the generalized weighted functional proportional mean is proposed and the parameter estimation method of its weighting coefficients by means of the algorithm of quadratic programming is given. This model has extensive representation. It is a new kind of aggregative method of group forecasting. By taking the suitable combining form of the forecasting models and seeking the optimal parameter, the optimal combining form can be obtained and the forecasting accuracy can be improved. The effectiveness of this model is demonstrated by an example.
基金the Postdoctoral Science Foundation of China(No.2015M582881)
文摘The autonomous route planning in coverage search is an important subject of unmanned aerial vehicle(UAV) mission planning. Pre-planning is simple and feasible for the coverage search mission of single UAV in regular areas. As to the dynamic mission in complicated environment of multi-UAV, the route planning will encounter the difficulties of reasonable task distribution and the real-time environment changes which include the changes of the mission area, the detection of threat area, the interference of communication and so on. At this point, making the UAV to do real-time autonomous planning is necessary. However, it is hard to fulfil requirements of real-time, autonomous and efficient at the same time. According to a scalable knowledge base,this paper proposes a coverage search algorithm which is based on the mapping between the basic behavior combination and surroundings. A UAV's coverage search simulation model with random shapes is built with a discrete map to update the environment and the changes of the mission on time. Comparison of the simulation analysis and the dynamic programming shows that the method has amazing expandability and can change the search strategy feasibly. It is efficient, and the ratio of coverage redundancy can be decreased to 1.21. It also has the potentiality in real-time calculation, and the computing time can be shortened to about 2 s.
文摘Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
