Traveling salesman problem(TSP) is one of the typical NP-hard problems, and it has been used in many engineering applications. However, the previous swarm intelligence(SI) based algorithms for TSP cannot coordinate wi...Traveling salesman problem(TSP) is one of the typical NP-hard problems, and it has been used in many engineering applications. However, the previous swarm intelligence(SI) based algorithms for TSP cannot coordinate with the exploration and exploitation abilities and are easily trapped into local optimum. In order to deal with this situation, a new hybrid optimization algorithm based on wolf pack search and local search(WPS-LS)is proposed for TSP. The new method firstly simulates the predatory process of wolf pack from the broad field to a specific place so that it allows for a search through all possible solution spaces and prevents wolf individuals from getting trapped into local optimum. Then, local search operation is used in the algorithm to improve the speed of solving and the accuracy of solution. The test of benchmarks selected from TSPLIB shows that the results obtained by this algorithm are better and closer to the theoretical optimal values with better robustness than those obtained by other methods.展开更多
For combinatorial system of multilayer dynamics of fluids in porous media, the second order and first order upwind finite difference fractional steps schemes applicable to parallel arithmetic are put forward and two-d...For combinatorial system of multilayer dynamics of fluids in porous media, the second order and first order upwind finite difference fractional steps schemes applicable to parallel arithmetic are put forward and two-dimensional and three-dimensional schemes are used to form a complete set. Some techniques, such as implicit-explicit difference scheme, calculus of variations, multiplicative commutation rule of difference operators, decomposition of high order difference operators and prior estimates, are adopted. Optimal order estimates in L 2 norm are derived to determine the error in the second order approximate solution. This method has already been applied to the numerical simulation of migration-accumulation of oil resources. Keywords: combinatorial system, multilayer dynamics of fluids in porous media, two-class upwind finite difference fractional steps method, convergence, numerical simulation of energy sources.展开更多
Cellular immune responses,particularly those associated with CD3+CD8+ cytotoxic T lymphocytes (CTL),are critical factors in controlling viral infection.Nasopharyngeal carcinoma (NPC) is closely associated with persist...Cellular immune responses,particularly those associated with CD3+CD8+ cytotoxic T lymphocytes (CTL),are critical factors in controlling viral infection.Nasopharyngeal carcinoma (NPC) is closely associated with persistent Epstein-Barr virus (EBV) infection.NPC vaccine studies have focused on enhancing specific antiviral CTL responses.In this study,three vaccines capable of expressing the EBV-latent membrane protein 2 (LMP2) (a DNA vector,an adeno-associated virus (AAV) vector,and a replication-defective adenovirus serotype 5 (Ad5) vector) were respectively used to immunize female Balb/c mice (4-6 weeks old) at weeks 0,2 and 4,either alone or in combination.Our results suggest that combined immunization with DNA,AAV,and adenovirus vector vaccines induced specific cellular immunity more effectively than any of these vectors alone or a combination of two of the three,constituting a sound vaccine strategy for the prevention and treatment of NPC.展开更多
A hyper-heuristic algorithm is a general solution framework that adaptively selects the optimizer to address complex problems.A classical hyper-heuristic framework consists of two levels,including the high-level heuri...A hyper-heuristic algorithm is a general solution framework that adaptively selects the optimizer to address complex problems.A classical hyper-heuristic framework consists of two levels,including the high-level heuristic and a set of low-level heuristics.The low-level heuristics to be used in the optimization process are chosen by the high-level tactics in the hyper-heuristic.In this study,a Cooperative Multi-Stage Hyper-Heuristic(CMS-HH)algorithm is proposed to address certain combinatorial optimization problems.In the CMS-HH,a genetic algorithm is introduced to perturb the initial solution to increase the diversity of the solution.In the search phase,an online learning mechanism based on the multi-armed bandits and relay hybridization technology are proposed to improve the quality of the solution.In addition,a multi-point search is introduced to cooperatively search with a single-point search when the state of the solution does not change in continuous time.The performance of the CMS-HH algorithm is assessed in six specific combinatorial optimization problems,including Boolean satisfiability problems,one-dimensional packing problems,permutation flow-shop scheduling problems,personnel scheduling problems,traveling salesman problems,and vehicle routing problems.The experimental results demonstrate the efficiency and significance of the proposed CMS-HH algorithm.展开更多
Increasing the self-resistance levels of Streptomyces is an effective strategy to improve the production of antibiotics.To increase the oxytetracycline(OTC) production in Streptomyces rimosus,we investigated the coope...Increasing the self-resistance levels of Streptomyces is an effective strategy to improve the production of antibiotics.To increase the oxytetracycline(OTC) production in Streptomyces rimosus,we investigated the cooperative effect of three co-overexpressing OTC resistance genes:one gene encodes a ribosomal protection protein(otrA) and the other two express efflux proteins(otrB and otrC).Results indicated that combinational overexpression of otrA,otrB,and otrC(MKABC) exerted a synergetic effect.OTC production increased by 179%in the recombinant strain compared with that of the wild-type strain M4018.The resistance level to OTC was increased by approximately two-fold relative to the parental strain,thereby indicating that applying the cooperative effect of self-resistance genes is useful to improve OTC production.Furthermore,the previously identified cluster-situated activator OtcR was overexpressed in MKABC in constructing the recombinant strain MKRABC;such strain can produce OTC of approximately7.49 g L^((-1)),which represents an increase of 19%in comparison with that of the OtcR-overexpressing strain alone.Our work showed that the cooperative overexpression of self-resistance genes is a promising strategy to enhance the antibiotics production in Streptomyces.展开更多
As a class of newly emerging material, liquid metal exhibits many outstanding performances in a wide variety of thermal management areas, such as thermal interface material, heat spreader, convective cooling and phase...As a class of newly emerging material, liquid metal exhibits many outstanding performances in a wide variety of thermal management areas, such as thermal interface material, heat spreader, convective cooling and phase change material （PCM） for thermal buffering etc. To help mold next generation unconventional cooling technologies and further advance the liquid metal cooling to an ever higher level in tackling more extreme, complex and critical thermal issues and energy utilizations, a novel conceptual scientific category was dedicated here which could be termed as combinatorial liquid metal heat transfer science. Through comprehensive interpretations on a group of representative liquid metal thermal management strategies, the most basic ways were outlined for developing liquid metal enabled combined cooling systems. The main scientific and technical features of the proposed hybrid cooling systems were illustrated. Particularly, five abstractive segments toward constructing the combinatorial liquid metal heat transfer systems were clarified. The most common methods on innovating liquid metal combined cooling systems based on this classification principle were discussed, and their potential utilization forms were proposed. For illustration purpose, several typical examples such as low melting point metal PCM combined cooling systems and liquid metal convection combined cooling systems, etc. were specifically introduced. Finally, future prospects to search for and make full use of the liquid metal combined high performance cooling system were discussed. It is expected that in practical application in the future, more unconventional combination forms on the liquid metal cooling can be obtained from the current fundamental principles.展开更多
Conflict avoidance （CA） plays a crucial role in guaranteeing the airspace safety. The cur- rent approaches, mostly focusing on a short-term situation which eliminates conflicts via local adjust- ment, cannot provide...Conflict avoidance （CA） plays a crucial role in guaranteeing the airspace safety. The cur- rent approaches, mostly focusing on a short-term situation which eliminates conflicts via local adjust- ment, cannot provide a global solution. Recently, long-term conflict avoidance approaches, which are proposed to provide solutions via strategically planning traffic flow from a global view, have attracted more attentions. With consideration of the situation in China, there are thousands of flights per day and the air route network is large and complex, which makes the long-term problem to be a large-scale combinatorial optimization problem with complex constraints. To minimize the risk of premature convergence being faced by current approaches and obtain higher quality solutions, in this work, we present an effective strategic framework based on a memetic algorithm （MA）, which can markedly improve search capability via a combination of population-based global search and local improve- ments made by individuals. In addition, a specially designed local search operator and an adaptive local search frequency strategy are proposed to improve the solution quality. Furthermore, a fast genetic algorithm （GA） is presented as the global optimization method. Empirical studies using real traffic data of the Chinese air route network and daily flight plans show that our approach outper- formed the existing approaches including the GA .based approach and the cooperative coevolution based approach as well as some well-known memetic algorithm based approaches.展开更多
Based on the analysis of previous genetic algorithms (GAs) for TSP, a novel method called Ge- GA is proposed. It combines gene pool and GA so as to direct the evolution of the whole population. The core of Ge- GA is t...Based on the analysis of previous genetic algorithms (GAs) for TSP, a novel method called Ge- GA is proposed. It combines gene pool and GA so as to direct the evolution of the whole population. The core of Ge- GA is the construction of gene pool and how to apply it to GA. Different from standard GAs, Ge- GA aims to enhance the ability of exploration and exploitation by incorporating global search with local search. On one hand a local search called Ge- Lo-calSearch operator is proposed to improve the solution quality, on the other hand the modified Inver-Over operator called Ge InverOver is considered as a global search mechanism to expand solution space of local minimal. Both of these operators are based on the gene pool. Our algorithm is applied to 11 well-known traveling salesman problems whose numbers of cities are from 70 to 1577 cities. The experiments results indicate that Ge- GA has great robustness for TSP. For each test instance, the average value of solution quality, found in accepted time, stays within 0. 001% from the optimum.展开更多
There is an urgent need for new antifungal agents to treat or combat fungal infection in humans and plants.Antifungal nucleoside antibiotics are an important family of natural products with distinctive structural feat...There is an urgent need for new antifungal agents to treat or combat fungal infection in humans and plants.Antifungal nucleoside antibiotics are an important family of natural products with distinctive structural features.Understanding their biosynthetic machinery is of great importance for the improvement of antibiotics titers.More importantly,it is a requisite for combinatorial biosynthesis to create hybrid nucleoside antibiotics.We herein focus on findings on the natural and designed biosynthesis of this important family of nucleoside antibiotics.展开更多
Hopfield neural network is a single layer feedforward neural network. Hopfield network requires some control parameters to be carefully selected, else the network is apt to converge to local minimum. An ant system is ...Hopfield neural network is a single layer feedforward neural network. Hopfield network requires some control parameters to be carefully selected, else the network is apt to converge to local minimum. An ant system is a nature inspired meta heuristic algorithm. It has been applied to several combinatorial optimization problems such as Traveling Salesman Problem, Scheduling Problems, etc. This paper will show an ant system may be used in tuning the network control parameters by a group of cooperated ants. The major advantage of this network is to adjust the network parameters automatically, avoiding a blind search for the set of control parameters. This network was tested on two TSP problems, 5 cities and 10 cities. The results have shown an obvious improvement.展开更多
Therapeutic targeting FOxO3A(a forkhead transcription factor)represents a prom-ising strategy to suppress acute myeloid leukemia(AML).However,the effective inhibitors that target FOXO3A are lacking and the adaptive re...Therapeutic targeting FOxO3A(a forkhead transcription factor)represents a prom-ising strategy to suppress acute myeloid leukemia(AML).However,the effective inhibitors that target FOXO3A are lacking and the adaptive response signaling weakens the cytotoxic effect of FOxO3A depletion on AML cells.Here,we show that FOxO3A deficiency induces a compensa-tory response involved in the reactive activation of mTOR that leads to signaling rebound and adaptive resistance.Mitochondrial metabolism acts downstream of mTOR to provoke activa-tion of JNK/c-JUN via reactive oxygen species(ROS).At the molecular level,FOXO3A directly binds to the promoter of G protein gamma subunit 7(GNG7)and preserves its expression,while GNG7 interacts with mTOR and restricts phosphorylated activation of mTOR.Consequently,combinatorial inhibition of FOXO3A and mTOR show a synergistic cytotoxic effect on AML cells and prolongs survival in a mouse model of AML.Through a structure-based virtual screening,we report one potent small-molecule FOxO3A inhibitor(Gardenoside)that exhibits a strong effect of anti-FOXO3A DNA binding.Gardenoside synergizes with rapamycin to substantially reduce tumor burden and extend survival in AML patient-derived xenograft model.These results demonstrate that mTOR can mediate adaptive resistance to FOxO3A inhibition and validate a combinatorial approach for treating AML.展开更多
Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecu...Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecule drugs,proteins and peptides,and nucleic acids.However,as the physicochemical properties of small-and macromolecular cargos can vary drastically,every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner.Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery.In this Review,we highlight our recent progress in the design,synthesis,characterization,evaluation,and optimization of combinatorial LNPs with novel structures and properties for the delivery of small-and macromolecular therapeutics both in vitro and in vivo.These delivery systems have enormous potentials for cancer therapy,antimicrobial applications,gene silencing,genome editing,and more.We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.展开更多
The problem of relevant enumeration with pattern-avoiding permutations is a significant topic in enumerative combinatorics and has wide applications in physics,chemistry,and computer science.This paper summarizes the ...The problem of relevant enumeration with pattern-avoiding permutations is a significant topic in enumerative combinatorics and has wide applications in physics,chemistry,and computer science.This paper summarizes the relevant conclusions of the enumeration of pattern-avoiding permutations on the nelement symmetric group Sn,alternating permutations,Dumont permutations,Ballot permutations,and inversion sequences.It also introduces relevant research results on avoiding vincular patterns and barred patterns in S_(n).展开更多
In dentistry, panoramic X-ray images are extensively used by dentists for tooth structure analysis and disease diagnosis. However, the manual analysis of these images is time-consuming and prone to misdiagnosis or ove...In dentistry, panoramic X-ray images are extensively used by dentists for tooth structure analysis and disease diagnosis. However, the manual analysis of these images is time-consuming and prone to misdiagnosis or overlooked. While deep learning techniques have been employed to segment teeth in panoramic X-ray images, accurate segmentation of individual teeth remains an underexplored area. In this study, we propose an end-to-end deep learning method that effectively addresses this challenge by employing an improved combinatorial loss function to separate the boundaries of adjacent teeth, enabling precise segmentation of individual teeth in panoramic X-ray images. We validate the feasibility of our approach using a challenging dataset. By training our segmentation network on 115 panoramic X-ray images, we achieve an intersection over union (IoU) of 86.56% for tooth segmentation and an accuracy of 65.52% in tooth counting on 87 test set images. Experimental results demonstrate the significant improvement of our proposed method in single tooth segmentation compared to existing methods.展开更多
基金supported by National Natural Science Foundation of China(61425008,61333004,61273054)Top-Notch Young Talents Program of China,and Aeronautical Foundation of China(2013585104)
基金the National Natural Science Foundation of China(No.61502198)the Science&Technology Development Project of Jilin Province(Nos.20180101334JC and 20190302117GX)the"3th-Five Year" Science and Technology Research Project of Education Department of Jilin Province(No.JJKH20170574KJ)
文摘Traveling salesman problem(TSP) is one of the typical NP-hard problems, and it has been used in many engineering applications. However, the previous swarm intelligence(SI) based algorithms for TSP cannot coordinate with the exploration and exploitation abilities and are easily trapped into local optimum. In order to deal with this situation, a new hybrid optimization algorithm based on wolf pack search and local search(WPS-LS)is proposed for TSP. The new method firstly simulates the predatory process of wolf pack from the broad field to a specific place so that it allows for a search through all possible solution spaces and prevents wolf individuals from getting trapped into local optimum. Then, local search operation is used in the algorithm to improve the speed of solving and the accuracy of solution. The test of benchmarks selected from TSPLIB shows that the results obtained by this algorithm are better and closer to the theoretical optimal values with better robustness than those obtained by other methods.
基金This work was supported by the Major State Basic Research Program of China(Grant No. 1990328) the National Tackling Key Problem Program, the National Natural Science Foundation of China (Grant Nos. 19871051 and 19972039) the Doctorate Foundation
文摘For combinatorial system of multilayer dynamics of fluids in porous media, the second order and first order upwind finite difference fractional steps schemes applicable to parallel arithmetic are put forward and two-dimensional and three-dimensional schemes are used to form a complete set. Some techniques, such as implicit-explicit difference scheme, calculus of variations, multiplicative commutation rule of difference operators, decomposition of high order difference operators and prior estimates, are adopted. Optimal order estimates in L 2 norm are derived to determine the error in the second order approximate solution. This method has already been applied to the numerical simulation of migration-accumulation of oil resources. Keywords: combinatorial system, multilayer dynamics of fluids in porous media, two-class upwind finite difference fractional steps method, convergence, numerical simulation of energy sources.
基金supported by the National High Technology Research and Development Program of China(Grant No. 2006AA02A229)
文摘Cellular immune responses,particularly those associated with CD3+CD8+ cytotoxic T lymphocytes (CTL),are critical factors in controlling viral infection.Nasopharyngeal carcinoma (NPC) is closely associated with persistent Epstein-Barr virus (EBV) infection.NPC vaccine studies have focused on enhancing specific antiviral CTL responses.In this study,three vaccines capable of expressing the EBV-latent membrane protein 2 (LMP2) (a DNA vector,an adeno-associated virus (AAV) vector,and a replication-defective adenovirus serotype 5 (Ad5) vector) were respectively used to immunize female Balb/c mice (4-6 weeks old) at weeks 0,2 and 4,either alone or in combination.Our results suggest that combined immunization with DNA,AAV,and adenovirus vector vaccines induced specific cellular immunity more effectively than any of these vectors alone or a combination of two of the three,constituting a sound vaccine strategy for the prevention and treatment of NPC.
基金supported by the National Key Research and Development Plan(No.2020YFB1713600)the National Natural Science Foundation of China(No.62063021)+2 种基金the Lanzhou Science Bureau Project(No.2018-rc-98)Public Welfare Project of Zhejiang Natural Science Foundation(No.LGJ19E050001)Project of Zhejiang Natural Science Foundation(No.LQ20F020011).
文摘A hyper-heuristic algorithm is a general solution framework that adaptively selects the optimizer to address complex problems.A classical hyper-heuristic framework consists of two levels,including the high-level heuristic and a set of low-level heuristics.The low-level heuristics to be used in the optimization process are chosen by the high-level tactics in the hyper-heuristic.In this study,a Cooperative Multi-Stage Hyper-Heuristic(CMS-HH)algorithm is proposed to address certain combinatorial optimization problems.In the CMS-HH,a genetic algorithm is introduced to perturb the initial solution to increase the diversity of the solution.In the search phase,an online learning mechanism based on the multi-armed bandits and relay hybridization technology are proposed to improve the quality of the solution.In addition,a multi-point search is introduced to cooperatively search with a single-point search when the state of the solution does not change in continuous time.The performance of the CMS-HH algorithm is assessed in six specific combinatorial optimization problems,including Boolean satisfiability problems,one-dimensional packing problems,permutation flow-shop scheduling problems,personnel scheduling problems,traveling salesman problems,and vehicle routing problems.The experimental results demonstrate the efficiency and significance of the proposed CMS-HH algorithm.
基金supported by funding from Shengxue Dacheng Pharmaceutical Co.,Ltd,National Natural Science Foundation of China(31400034 and 31570031)the Ministry of Science and Technology of China(2013CB734001)
文摘Increasing the self-resistance levels of Streptomyces is an effective strategy to improve the production of antibiotics.To increase the oxytetracycline(OTC) production in Streptomyces rimosus,we investigated the cooperative effect of three co-overexpressing OTC resistance genes:one gene encodes a ribosomal protection protein(otrA) and the other two express efflux proteins(otrB and otrC).Results indicated that combinational overexpression of otrA,otrB,and otrC(MKABC) exerted a synergetic effect.OTC production increased by 179%in the recombinant strain compared with that of the wild-type strain M4018.The resistance level to OTC was increased by approximately two-fold relative to the parental strain,thereby indicating that applying the cooperative effect of self-resistance genes is useful to improve OTC production.Furthermore,the previously identified cluster-situated activator OtcR was overexpressed in MKABC in constructing the recombinant strain MKRABC;such strain can produce OTC of approximately7.49 g L^((-1)),which represents an increase of 19%in comparison with that of the OtcR-overexpressing strain alone.Our work showed that the cooperative overexpression of self-resistance genes is a promising strategy to enhance the antibiotics production in Streptomyces.
文摘As a class of newly emerging material, liquid metal exhibits many outstanding performances in a wide variety of thermal management areas, such as thermal interface material, heat spreader, convective cooling and phase change material （PCM） for thermal buffering etc. To help mold next generation unconventional cooling technologies and further advance the liquid metal cooling to an ever higher level in tackling more extreme, complex and critical thermal issues and energy utilizations, a novel conceptual scientific category was dedicated here which could be termed as combinatorial liquid metal heat transfer science. Through comprehensive interpretations on a group of representative liquid metal thermal management strategies, the most basic ways were outlined for developing liquid metal enabled combined cooling systems. The main scientific and technical features of the proposed hybrid cooling systems were illustrated. Particularly, five abstractive segments toward constructing the combinatorial liquid metal heat transfer systems were clarified. The most common methods on innovating liquid metal combined cooling systems based on this classification principle were discussed, and their potential utilization forms were proposed. For illustration purpose, several typical examples such as low melting point metal PCM combined cooling systems and liquid metal convection combined cooling systems, etc. were specifically introduced. Finally, future prospects to search for and make full use of the liquid metal combined high performance cooling system were discussed. It is expected that in practical application in the future, more unconventional combination forms on the liquid metal cooling can be obtained from the current fundamental principles.
基金co-supported by the National High-tech Research and Development Program of China (Grant No.2011AA110101)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 60921001)China Scholarship Council
文摘Conflict avoidance （CA） plays a crucial role in guaranteeing the airspace safety. The cur- rent approaches, mostly focusing on a short-term situation which eliminates conflicts via local adjust- ment, cannot provide a global solution. Recently, long-term conflict avoidance approaches, which are proposed to provide solutions via strategically planning traffic flow from a global view, have attracted more attentions. With consideration of the situation in China, there are thousands of flights per day and the air route network is large and complex, which makes the long-term problem to be a large-scale combinatorial optimization problem with complex constraints. To minimize the risk of premature convergence being faced by current approaches and obtain higher quality solutions, in this work, we present an effective strategic framework based on a memetic algorithm （MA）, which can markedly improve search capability via a combination of population-based global search and local improve- ments made by individuals. In addition, a specially designed local search operator and an adaptive local search frequency strategy are proposed to improve the solution quality. Furthermore, a fast genetic algorithm （GA） is presented as the global optimization method. Empirical studies using real traffic data of the Chinese air route network and daily flight plans show that our approach outper- formed the existing approaches including the GA .based approach and the cooperative coevolution based approach as well as some well-known memetic algorithm based approaches.
基金Supported by the National Natural Science Foundation of China(70071042,60073043,and 60133010)
文摘Based on the analysis of previous genetic algorithms (GAs) for TSP, a novel method called Ge- GA is proposed. It combines gene pool and GA so as to direct the evolution of the whole population. The core of Ge- GA is the construction of gene pool and how to apply it to GA. Different from standard GAs, Ge- GA aims to enhance the ability of exploration and exploitation by incorporating global search with local search. On one hand a local search called Ge- Lo-calSearch operator is proposed to improve the solution quality, on the other hand the modified Inver-Over operator called Ge InverOver is considered as a global search mechanism to expand solution space of local minimal. Both of these operators are based on the gene pool. Our algorithm is applied to 11 well-known traveling salesman problems whose numbers of cities are from 70 to 1577 cities. The experiments results indicate that Ge- GA has great robustness for TSP. For each test instance, the average value of solution quality, found in accepted time, stays within 0. 001% from the optimum.
基金supported by grants from the Ministry of Science and Technology of China(2013CB 734001)the National Natural Science Foundation of China(31470206 and 31571281)
文摘There is an urgent need for new antifungal agents to treat or combat fungal infection in humans and plants.Antifungal nucleoside antibiotics are an important family of natural products with distinctive structural features.Understanding their biosynthetic machinery is of great importance for the improvement of antibiotics titers.More importantly,it is a requisite for combinatorial biosynthesis to create hybrid nucleoside antibiotics.We herein focus on findings on the natural and designed biosynthesis of this important family of nucleoside antibiotics.
文摘Hopfield neural network is a single layer feedforward neural network. Hopfield network requires some control parameters to be carefully selected, else the network is apt to converge to local minimum. An ant system is a nature inspired meta heuristic algorithm. It has been applied to several combinatorial optimization problems such as Traveling Salesman Problem, Scheduling Problems, etc. This paper will show an ant system may be used in tuning the network control parameters by a group of cooperated ants. The major advantage of this network is to adjust the network parameters automatically, avoiding a blind search for the set of control parameters. This network was tested on two TSP problems, 5 cities and 10 cities. The results have shown an obvious improvement.
基金supported by the Chongqing Science Fund for Distinguished Young Scholars,China(C(STB2022NSCQJQX0032)National Science Foundation of China(No.81970100,82170115 and 81700135)the Doctor Research Project of Chongqing,China(No.CSTB2022BSXMJCX0005)。
文摘Therapeutic targeting FOxO3A(a forkhead transcription factor)represents a prom-ising strategy to suppress acute myeloid leukemia(AML).However,the effective inhibitors that target FOXO3A are lacking and the adaptive response signaling weakens the cytotoxic effect of FOxO3A depletion on AML cells.Here,we show that FOxO3A deficiency induces a compensa-tory response involved in the reactive activation of mTOR that leads to signaling rebound and adaptive resistance.Mitochondrial metabolism acts downstream of mTOR to provoke activa-tion of JNK/c-JUN via reactive oxygen species(ROS).At the molecular level,FOXO3A directly binds to the promoter of G protein gamma subunit 7(GNG7)and preserves its expression,while GNG7 interacts with mTOR and restricts phosphorylated activation of mTOR.Consequently,combinatorial inhibition of FOXO3A and mTOR show a synergistic cytotoxic effect on AML cells and prolongs survival in a mouse model of AML.Through a structure-based virtual screening,we report one potent small-molecule FOxO3A inhibitor(Gardenoside)that exhibits a strong effect of anti-FOXO3A DNA binding.Gardenoside synergizes with rapamycin to substantially reduce tumor burden and extend survival in AML patient-derived xenograft model.These results demonstrate that mTOR can mediate adaptive resistance to FOxO3A inhibition and validate a combinatorial approach for treating AML.
基金supported by the National Institutes of Health(NIH)Grants R01 EB027170-04 and UG3 TR002636-01,USA。
文摘Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecule drugs,proteins and peptides,and nucleic acids.However,as the physicochemical properties of small-and macromolecular cargos can vary drastically,every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner.Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery.In this Review,we highlight our recent progress in the design,synthesis,characterization,evaluation,and optimization of combinatorial LNPs with novel structures and properties for the delivery of small-and macromolecular therapeutics both in vitro and in vivo.These delivery systems have enormous potentials for cancer therapy,antimicrobial applications,gene silencing,genome editing,and more.We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.
文摘The problem of relevant enumeration with pattern-avoiding permutations is a significant topic in enumerative combinatorics and has wide applications in physics,chemistry,and computer science.This paper summarizes the relevant conclusions of the enumeration of pattern-avoiding permutations on the nelement symmetric group Sn,alternating permutations,Dumont permutations,Ballot permutations,and inversion sequences.It also introduces relevant research results on avoiding vincular patterns and barred patterns in S_(n).
文摘In dentistry, panoramic X-ray images are extensively used by dentists for tooth structure analysis and disease diagnosis. However, the manual analysis of these images is time-consuming and prone to misdiagnosis or overlooked. While deep learning techniques have been employed to segment teeth in panoramic X-ray images, accurate segmentation of individual teeth remains an underexplored area. In this study, we propose an end-to-end deep learning method that effectively addresses this challenge by employing an improved combinatorial loss function to separate the boundaries of adjacent teeth, enabling precise segmentation of individual teeth in panoramic X-ray images. We validate the feasibility of our approach using a challenging dataset. By training our segmentation network on 115 panoramic X-ray images, we achieve an intersection over union (IoU) of 86.56% for tooth segmentation and an accuracy of 65.52% in tooth counting on 87 test set images. Experimental results demonstrate the significant improvement of our proposed method in single tooth segmentation compared to existing methods.
