Deadlock resolution strategies based on siphon control are widely investigated.Their computational efficiency largely depends on siphon computation.Mixed-integer programming(MIP)can be utilized for the computation of ...Deadlock resolution strategies based on siphon control are widely investigated.Their computational efficiency largely depends on siphon computation.Mixed-integer programming(MIP)can be utilized for the computation of an emptiable siphon in a Petri net(PN).Based on it,deadlock resolution strategies can be designed without requiring complete siphon enumeration that has exponential complexity.Due to this reason,various MIP methods are proposed for various subclasses of PNs.This work proposes an innovative MIP method to compute an emptiable minimal siphon(EMS)for a subclass of PNs named S^(4)PR.In particular,many particular structural characteristics of EMS in S4 PR are formalized as constraints,which greatly reduces the solution space.Experimental results show that the proposed MIP method has higher computational efficiency.Furthermore,the proposed method allows one to determine the liveness of an ordinary S^(4)PR.展开更多
The double row layout problem(DRLP)is to assign facilities on two rows in parallel so that the total cost of material handling among facilities is minimized.Since it is vital to save cost and enhance productivity,the ...The double row layout problem(DRLP)is to assign facilities on two rows in parallel so that the total cost of material handling among facilities is minimized.Since it is vital to save cost and enhance productivity,the DRLP plays an important role in many application fields.Nevertheless,it is very hard to handle the DRLP because of its complex model.In this paper,we consider a new simplified model for the DRLP(SM-DRLP)and provide a mixed integer programming(MIP)formulation for it.The continuous decision variables of the DRLP are divided into two parts:start points of double rows and adjustable clearances between adjacent facilities.The former one is considered in the new simplified model for the DRLP with the purpose of maintaining solution quality,while the latter one is not taken into account with the purpose of reducing computational time.To evaluate its performance,our SM-DRLP is compared with the model of a general DRLP and the model of another simplified DRLP.The experimental results show the efficiency of our proposed model.展开更多
During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive...During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h^(2)/(4√2),where h is the piecewise length.展开更多
Two classes of mixed-integer nonlinear bilevel programming problems are discussed. One is that the follower＇s functions are separable with respect to the follower＇s variables, and the other is that the follower＇s f...Two classes of mixed-integer nonlinear bilevel programming problems are discussed. One is that the follower＇s functions are separable with respect to the follower＇s variables, and the other is that the follower＇s functions are convex if the follower＇s variables are not restricted to integers. A genetic algorithm based on an exponential distribution is proposed for the aforementioned problems. First, for each fixed leader＇s variable x, it is proved that the optimal solution y of the follower＇s mixed-integer programming can be obtained by solving associated relaxed problems, and according to the convexity of the functions involved, a simplified branch and bound approach is given to solve the follower＇s programming for the second class of problems. Furthermore, based on an exponential distribution with a parameter λ, a new crossover operator is designed in which the best individuals are used to generate better offspring of crossover. The simulation results illustrate that the proposed algorithm is efficient and robust.展开更多
Many important integer and mixed-integer programming problems are difficult to solve.A representative example is unit commitment with combined cycle units and transmission capacity constraints.Complicated transitions ...Many important integer and mixed-integer programming problems are difficult to solve.A representative example is unit commitment with combined cycle units and transmission capacity constraints.Complicated transitions within combined cycle units are difficult to follow,and system-wide coupling transmission capacity constraints are difficult to handle.Another example is the quadratic assignment problem.The presence of cross-products in the objective function leads to nonlinearity.In this study,building upon the novel integration of surrogate Lagrangian relaxation and branch-and-cut,such problems will be solved by relaxing selected coupling constraints.Monotonicity of the relaxed problem will be assumed and exploited and nonlinear terms will be dynamically linearised.The linearity of the resulting problem will be exploited using branch-and-cut.To achieve fast convergence,guidelines for selecting stepsizing parameters will be developed.The method opens up directions for solving nonlinear mixed-integer problems,and numerical results indicate that the new method is efficient.展开更多
The modeling flexibility and the optimality guarantees provided by mixed-integer programming greatly aid the design of robust and future-proof decision support systems.The complexity of industrial-scale supply chain o...The modeling flexibility and the optimality guarantees provided by mixed-integer programming greatly aid the design of robust and future-proof decision support systems.The complexity of industrial-scale supply chain optimization,however,often poses limits to the application of general mixed-integer programming solvers.In this paper we describe algorithmic innovations that help to ensure that MIP solver performance matches the complexity of the large supply chain problems and tight time limits encountered in practice.Our computational evaluation is based on a diverse set,modeling real-world scenarios supplied by our industry partner SAP.展开更多
Most existing distribution networks are difficult to withstand the impact of meteorological disasters. With the development of active distribution networks(ADNs), more and more upgrading and updating resources are app...Most existing distribution networks are difficult to withstand the impact of meteorological disasters. With the development of active distribution networks(ADNs), more and more upgrading and updating resources are applied to enhance the resilience of ADNs. A two-stage stochastic mixed-integer programming(SMIP) model is proposed in this paper to minimize the upgrading and operation cost of ADNs by considering random scenarios referring to different operation scenarios of ADNs caused by disastrous weather events. In the first stage, the planning decision is formulated according to the measures of hardening existing distribution lines, upgrading automatic switches, and deploying energy storage resources. The second stage is to evaluate the operation cost of ADNs by considering the cost of load shedding due to disastrous weather and optimal deployment of energy storage systems(ESSs) under normal weather condition. A novel modeling method is proposed to address the uncertainty of the operation state of distribution lines according to the canonical representation of logical constraints. The progressive hedging algorithm(PHA) is adopted to solve the SMIP model. The IEEE 33-node test system is employed to verify the feasibility and effectiveness of the proposed method. The results show that the proposed model can enhance the resilience of the ADN while ensuring economy.展开更多
Elementary siphons are useful in the development of a deadlock prevention policy for a discrete event system modeled with Petri nets. This paper proposes an algorithm to iteratively extract a set of elementary siphons...Elementary siphons are useful in the development of a deadlock prevention policy for a discrete event system modeled with Petri nets. This paper proposes an algorithm to iteratively extract a set of elementary siphons in a class of Petri nets, called system of simple sequential processes with resources （S3pR）. At each iteration, by a mixed-integer programming （MIP） method, the proposed algorithm finds a maximal unmarked siphon, classifies the places in it, extracts an elementary siphon from the classified places, and adds a new constraint in order to extract the next elementary siphon. This algorithm iteratively executes until no new unmarked siphons can be found. It finally obtains a unique set of elementary siphons and avoids a complete siphon enumeration. A theoretical analysis and examples are given to demonstrate its efficiency and practical potentials.展开更多
To properly describe and solve complex decision problems,research on theoretical properties and solution of mixed-integer quadratic programs is becoming very important.We establish in this paper different Lipschitz-ty...To properly describe and solve complex decision problems,research on theoretical properties and solution of mixed-integer quadratic programs is becoming very important.We establish in this paper different Lipschitz-type continuity results about the optimal value function and optimal solutions of mixed-integer parametric quadratic programs with parameters in the linear part of the objective function and in the right-hand sides of the linear constraints.The obtained results extend some existing results for continuous quadratic programs,and,more importantly,lay the foundation for further theoretical study and corresponding algorithm analysis on mixed-integer quadratic programs.展开更多
Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 str...Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.展开更多
Editor's Note In his keynote address at the opening ceremony of the Global Leaders'Meeting on Women,held in Beijing on October 13,2025,Chinese President Xi Jinping announced a series of measures China will tak...Editor's Note In his keynote address at the opening ceremony of the Global Leaders'Meeting on Women,held in Beijing on October 13,2025,Chinese President Xi Jinping announced a series of measures China will take,in the next five years,to further support the global cause of women.One of the measures is:China will launch 1,000"small and beautiful"livelihood programs with Chinese assistance that take women and girls as priority beneficiaries.展开更多
It is extremely challenging to solve the mixed-integer optimal control problems(MIOCPs)due to the complex computation in solving the integer decision variables.This paper presents a new method based on quantum anneali...It is extremely challenging to solve the mixed-integer optimal control problems(MIOCPs)due to the complex computation in solving the integer decision variables.This paper presents a new method based on quantum annealing(QA)to solve MIOCP.The QA is a metaheuristic which applies quantum tunneling in the annealing process.It has a faster convergence speed in optimal-searching and is less likely to run into local minima.Hence,QA is applied to deal with this kind of optimization problems.First,MIOCP is transformed into a mixed-integer nonlinear programming(MINLP).Then,a method based on QA is adopted to solve the MINLP and acquire the optimal solution.At last,two benchmark examples including Lotka-Volterra type fishing problem and distillation column are presented and solved.The effectiveness of the metliodology is verified by the acquired optimal schemes.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression i...BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both brea...BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.展开更多
基金supported in part by Zhejiang Provincial Key Research and Development Program(2018C01084)Zhejiang Natural Science Foundation(LQ20F020009)Zhejiang Gongshang University,Zhejiang Provincial Key Laboratory of New Network Standards and Technologies(2013E10012)。
文摘Deadlock resolution strategies based on siphon control are widely investigated.Their computational efficiency largely depends on siphon computation.Mixed-integer programming(MIP)can be utilized for the computation of an emptiable siphon in a Petri net(PN).Based on it,deadlock resolution strategies can be designed without requiring complete siphon enumeration that has exponential complexity.Due to this reason,various MIP methods are proposed for various subclasses of PNs.This work proposes an innovative MIP method to compute an emptiable minimal siphon(EMS)for a subclass of PNs named S^(4)PR.In particular,many particular structural characteristics of EMS in S4 PR are formalized as constraints,which greatly reduces the solution space.Experimental results show that the proposed MIP method has higher computational efficiency.Furthermore,the proposed method allows one to determine the liveness of an ordinary S^(4)PR.
基金Supported by the National Natural Science Foundation of China(61871204,62174033)the Natural Science Foundation of Fujian Province(2017J01767,2020J01843)+1 种基金the Program for New Century Excellent Talents in Fujian Province Universitythe Science and Technology Project of Minjiang University(MYK19017)。
文摘The double row layout problem(DRLP)is to assign facilities on two rows in parallel so that the total cost of material handling among facilities is minimized.Since it is vital to save cost and enhance productivity,the DRLP plays an important role in many application fields.Nevertheless,it is very hard to handle the DRLP because of its complex model.In this paper,we consider a new simplified model for the DRLP(SM-DRLP)and provide a mixed integer programming(MIP)formulation for it.The continuous decision variables of the DRLP are divided into two parts:start points of double rows and adjustable clearances between adjacent facilities.The former one is considered in the new simplified model for the DRLP with the purpose of maintaining solution quality,while the latter one is not taken into account with the purpose of reducing computational time.To evaluate its performance,our SM-DRLP is compared with the model of a general DRLP and the model of another simplified DRLP.The experimental results show the efficiency of our proposed model.
基金supported by the National Natural Sci‐ence Foundation of China(Grant No.62306325)。
文摘During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h^(2)/(4√2),where h is the piecewise length.
基金supported by the National Natural Science Fundation of China (60374063)
文摘Two classes of mixed-integer nonlinear bilevel programming problems are discussed. One is that the follower＇s functions are separable with respect to the follower＇s variables, and the other is that the follower＇s functions are convex if the follower＇s variables are not restricted to integers. A genetic algorithm based on an exponential distribution is proposed for the aforementioned problems. First, for each fixed leader＇s variable x, it is proved that the optimal solution y of the follower＇s mixed-integer programming can be obtained by solving associated relaxed problems, and according to the convexity of the functions involved, a simplified branch and bound approach is given to solve the follower＇s programming for the second class of problems. Furthermore, based on an exponential distribution with a parameter λ, a new crossover operator is designed in which the best individuals are used to generate better offspring of crossover. The simulation results illustrate that the proposed algorithm is efficient and robust.
基金supported by the United States National Science Foundation[grant numbers ECCS-1028870 and ECCS-1509666]and Southern California Edison.
文摘Many important integer and mixed-integer programming problems are difficult to solve.A representative example is unit commitment with combined cycle units and transmission capacity constraints.Complicated transitions within combined cycle units are difficult to follow,and system-wide coupling transmission capacity constraints are difficult to handle.Another example is the quadratic assignment problem.The presence of cross-products in the objective function leads to nonlinearity.In this study,building upon the novel integration of surrogate Lagrangian relaxation and branch-and-cut,such problems will be solved by relaxing selected coupling constraints.Monotonicity of the relaxed problem will be assumed and exploited and nonlinear terms will be dynamically linearised.The linearity of the resulting problem will be exploited using branch-and-cut.To achieve fast convergence,guidelines for selecting stepsizing parameters will be developed.The method opens up directions for solving nonlinear mixed-integer problems,and numerical results indicate that the new method is efficient.
文摘The modeling flexibility and the optimality guarantees provided by mixed-integer programming greatly aid the design of robust and future-proof decision support systems.The complexity of industrial-scale supply chain optimization,however,often poses limits to the application of general mixed-integer programming solvers.In this paper we describe algorithmic innovations that help to ensure that MIP solver performance matches the complexity of the large supply chain problems and tight time limits encountered in practice.Our computational evaluation is based on a diverse set,modeling real-world scenarios supplied by our industry partner SAP.
基金supported by National Natural Science Foundation of China (No. U1866603)Innovation Support Program of Chongqing for Preferential Returned Chinese Scholars (No. cx2021036)Natural Science Foundation of Chongqing,China (No. CSTB2022NSCQ-BHX0729)。
文摘Most existing distribution networks are difficult to withstand the impact of meteorological disasters. With the development of active distribution networks(ADNs), more and more upgrading and updating resources are applied to enhance the resilience of ADNs. A two-stage stochastic mixed-integer programming(SMIP) model is proposed in this paper to minimize the upgrading and operation cost of ADNs by considering random scenarios referring to different operation scenarios of ADNs caused by disastrous weather events. In the first stage, the planning decision is formulated according to the measures of hardening existing distribution lines, upgrading automatic switches, and deploying energy storage resources. The second stage is to evaluate the operation cost of ADNs by considering the cost of load shedding due to disastrous weather and optimal deployment of energy storage systems(ESSs) under normal weather condition. A novel modeling method is proposed to address the uncertainty of the operation state of distribution lines according to the canonical representation of logical constraints. The progressive hedging algorithm(PHA) is adopted to solve the SMIP model. The IEEE 33-node test system is employed to verify the feasibility and effectiveness of the proposed method. The results show that the proposed model can enhance the resilience of the ADN while ensuring economy.
基金supported by the Natural Science Foundation of China under Grant No.60773001,61074035, 61064003,and 50978129the Fundamental Research Funds for the Central Universities under Grant No. JY 10000904001+2 种基金the National Research Foundation for the Doctoral Program of Higher Education,the Ministry of Education,P.R.China,under Grant No.20090203110009the"863"High-tech Research and Development Program of China under Grant No.2008AA04Z 109the Alexander von Humboldt Foundation
文摘Elementary siphons are useful in the development of a deadlock prevention policy for a discrete event system modeled with Petri nets. This paper proposes an algorithm to iteratively extract a set of elementary siphons in a class of Petri nets, called system of simple sequential processes with resources （S3pR）. At each iteration, by a mixed-integer programming （MIP） method, the proposed algorithm finds a maximal unmarked siphon, classifies the places in it, extracts an elementary siphon from the classified places, and adds a new constraint in order to extract the next elementary siphon. This algorithm iteratively executes until no new unmarked siphons can be found. It finally obtains a unique set of elementary siphons and avoids a complete siphon enumeration. A theoretical analysis and examples are given to demonstrate its efficiency and practical potentials.
基金Supported by the National Natural Science Foundation of China(10571141,70971109)the Key Projectof the National Natural Science Foundation of China(70531030)
文摘To properly describe and solve complex decision problems,research on theoretical properties and solution of mixed-integer quadratic programs is becoming very important.We establish in this paper different Lipschitz-type continuity results about the optimal value function and optimal solutions of mixed-integer parametric quadratic programs with parameters in the linear part of the objective function and in the right-hand sides of the linear constraints.The obtained results extend some existing results for continuous quadratic programs,and,more importantly,lay the foundation for further theoretical study and corresponding algorithm analysis on mixed-integer quadratic programs.
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
文摘Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
基金The National Natural Science Foundation of China[72174184]provided policy and financialsupport for this research.
文摘Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
文摘The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
文摘Editor's Note In his keynote address at the opening ceremony of the Global Leaders'Meeting on Women,held in Beijing on October 13,2025,Chinese President Xi Jinping announced a series of measures China will take,in the next five years,to further support the global cause of women.One of the measures is:China will launch 1,000"small and beautiful"livelihood programs with Chinese assistance that take women and girls as priority beneficiaries.
基金the National Natural Science Foundation of China(No.61573378)the BUPT Excellent Ph.D.Students Foundation(No.CX2019113)。
文摘It is extremely challenging to solve the mixed-integer optimal control problems(MIOCPs)due to the complex computation in solving the integer decision variables.This paper presents a new method based on quantum annealing(QA)to solve MIOCP.The QA is a metaheuristic which applies quantum tunneling in the annealing process.It has a faster convergence speed in optimal-searching and is less likely to run into local minima.Hence,QA is applied to deal with this kind of optimization problems.First,MIOCP is transformed into a mixed-integer nonlinear programming(MINLP).Then,a method based on QA is adopted to solve the MINLP and acquire the optimal solution.At last,two benchmark examples including Lotka-Volterra type fishing problem and distillation column are presented and solved.The effectiveness of the metliodology is verified by the acquired optimal schemes.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
基金supported by Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.
