Cold spare is the most common configuration amongst the three types of configuration for systems used on board and for power generation systems. A new approach to calculate the unavailability of systems composed of id...Cold spare is the most common configuration amongst the three types of configuration for systems used on board and for power generation systems. A new approach to calculate the unavailability of systems composed of identical spares in cold spare configuration was proposed in this study. Instead of using the spare gate of dynamic fault tree( DFT) and the Markov analysis,AND gate of static fault tree used for calculating the unavailability of cold spare systems was proposed in this paper. By using this approach,unavailability of identical cold spare systems composed of nonrepairable spare components can be calculated exactly and systems composed of both repairable and nonreparable identical spare components can be estimated without building large Markov state diagram.展开更多
Based on an investigation on the current situation of SPM in some enterprises, this paper presents the common probletns and poor fields existing in SPM in enterprise; analyzes the reasons which resulted in the situati...Based on an investigation on the current situation of SPM in some enterprises, this paper presents the common probletns and poor fields existing in SPM in enterprise; analyzes the reasons which resulted in the situation, and then puts forward some feasible measures to improve it. Lastly, some fields that should be paid more attention in SPM are provided.展开更多
Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost （LCC）. With an analysis of various impacts on support system, the spares...Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost （LCC）. With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and con-sumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the （s-1, s） and （R, Q） inventory policy, the spares resup-ply model is established under the batch ordering policy based on inventory state, and the optimi-zation analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets：one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation;therefore, the model＇s correctness, method＇s validity as well as optimization project＇s rationality are proved to a certain extent.展开更多
Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- a...Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- anism. Here, we determined that spared nerve injury （SNI） increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia （DRG） neurons and satellite glial cells. SNI also induced long- lasting upregulation of CXCL12 and CXCR4 in the ipsi- lateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNI- induced a sustained increase in TNF-α expression in the DRG and spinal cord. Intraperitoneal injection （i.p.） of the TNF-α synthesis inhibitor thalidomide reduced the SNI-in- duced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection （i.t.） of the CXCR4 antagonist AMD3100, both 30 rain before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. admin- istration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the acti- vation of ERK in the spinal cord. The mechanical hyper- sensitivity induced in nai＇ve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-α might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL 12/CXCR4 sig- naling via ERK activation contributes to the development and maintenance of neuropathic pain.展开更多
Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair...Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair level focuses on economic analysis models which are used to optimize costs and rarely considers the maintenance time required by the implementation of the maintenance program. In fact, as to the system requiring high mission complete success, the maintenance time is an important factor which has a great influence on the availability of equipment systems. Considering the relationship between the maintenance time and the spares stocks level, it is obvious that there are contradictions between the maintenance time and the cost. In order to balance these two factors, it is necessary to build an optimization LORA model. To this end, the maintenance time representing performance characteristic is introduced, and on the basis of spares stocks which is traditionally regarded as a decision variable, a decision variable of repair level is added, and a multi-echelon multiindenture（MEMI） optimization LORA model is built which takes the best cost-effectiveness ratio as the criterion, the expected number of backorder（EBO） as the objective function and the cost as the constraint. Besides, the paper designs a convex programming algorithm of multi-variable for the optimization model, provides solutions to the non-convex objective function and methods for improving the efficiency of the algorithm. The method provided in this paper is proved to be credible and effective according to the numerical example and the simulation result.展开更多
In order to optimize the spares configuration project at different stages during the life cycle, the factor of time is considered to relax the assumption of the spares steady demand in multi-echelon technique for reco...In order to optimize the spares configuration project at different stages during the life cycle, the factor of time is considered to relax the assumption of the spares steady demand in multi-echelon technique for recoverable item control (METRIC) theory. According to the method of systems analysis, the dynamic palm theorem is introduced to establish the prediction model of the spares demand rate, and its main influence factors are analyzed, based on which, the spares support effectiveness evaluation index system is studied, and the system optimization-oriented spares dynamic configuration method for multi-echelon multi-indenture system is proposed. Through the analysis of the optimization algorithm, the layered marginal algorithm is designed to improve the model calculation efficiency. In a given example, the multi-stage spares configuration project during its life cycle is gotten, the research result conforms to the actual status, and it can provide a new way for the spares dynamic optimization.展开更多
A collaborative optimization model for maintenance and spare ordering of a single-unit degrading system is proposed in this paper based on the continuous detection. A gamma distribution is used to model the material d...A collaborative optimization model for maintenance and spare ordering of a single-unit degrading system is proposed in this paper based on the continuous detection. A gamma distribution is used to model the material degradation. The degrading decrement after the imperfect maintenance action is assumed as a random variable normal distribution. This model aims to ob- tain the optimal maintenance policy and spare ordering point with the expected cost rate within system lifecycle as the optimization objective. The rationality and feasibility of the model are proved through a numerical example.展开更多
Redundancy is a common structure for warship system,and it is an effective way to improve the reliability of the system.In this paper, warship system is taken as the object of study,based on the system reliability equ...Redundancy is a common structure for warship system,and it is an effective way to improve the reliability of the system.In this paper, warship system is taken as the object of study,based on the system reliability equivalence principle, a spares demand rate calculation method for redundant system is proposed through structure transformation. According to the system analysis method, the general modeling data structure of spares support echelon and system indenture is established, and the mission success probability is taken as the optimization target to build the dynamic optimization model of carrying spares during the process of multi-phase. By introducing the Lagrange multiplier, the spares weight, volume and cost are transformed to the single target of the spares total scale, and the initial Lagrange factors and its dynamic adjustment policy is proposed. In a given example, the main influence factors of the carrying spares project are analyzed, and the study results are in accordance with the reality, which can provide a new approach to mission-oriented carrying spares optimization for the redundant system.展开更多
With the wide application of condition based maintenance(CBM) in aircraft maintenance practice, the joint optimization of maintenance and inventory management, which can take full advantage of CBM and reduce the aircr...With the wide application of condition based maintenance(CBM) in aircraft maintenance practice, the joint optimization of maintenance and inventory management, which can take full advantage of CBM and reduce the aircraft operational cost, is receiving increasing attention. In order to optimize the inspection interval, maintenance decision and spare provisioning together for aircraft deteriorating parts, firstly, a joint inventory management strategy is presented, then, a joint optimization of maintenance inspection and spare provisioning for aircraft parts subject to the Wiener degradation process is proposed based on the strategy.Secondly, a combination of the genetic algorithm(GA) and the Monte Carol method is developed to minimize the total cost rate.Finally, a case study is conducted and the proposed joint optimization model is compared with the existing optimization model and the airline real case. The results demonstrate that the proposed model is more beneficial and effective. In addition, the sensitivity analysis of the proposed model shows that the lead time has higher influence on the optimal results than the urgent order cost and the corrective maintenance cost, which is consistent with the actual situation of aircraft maintenance practices and inventory management.展开更多
Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brushevoked dynamic and filament-evoked punctate mechanical allodyn...Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brushevoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1(Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury(SNI).Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in na¨?ve but also in ML133-pretreated mice. In contrast, bicuculline, a GABAAreceptor antagonist, induced only punctate, but not dynamic,allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents(gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration oracute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively.In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.展开更多
The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological condition...The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.展开更多
In equipment integrated logistics support(ILS), the supply capability of spare parts is a significant factor. There are lots of depots in the traditional support system, which makes too many redundant spare parts and ...In equipment integrated logistics support(ILS), the supply capability of spare parts is a significant factor. There are lots of depots in the traditional support system, which makes too many redundant spare parts and causes high cost of support. Meanwhile,the inconsistency among depots makes it difficult to manage spare parts. With the development of information technology and transportation, the supply network has become more efficient. In order to further improve the efficiency of supply-support work and the availability of the equipment system, building a system of one centralized depot with multiple depots becomes an appropriate way.In this case, location selection of the depots including centralized depots and multiple depots becomes a top priority in the support system. This paper will focus on the location selection problem of centralized depots considering ILS factors. Unlike the common location selection problem, depots in ILS require a higher service level. Therefore, it becomes desperately necessary to take the high requirement of the mission into account while determining location of depots. Based on this, we raise an optimal depot location model. First, the expected transportation cost is calculated.Next, factors in ILS such as response time, availability and fill rate are analyzed for evaluating positions of open depots. Then, an optimization model of depot location is developed with the minimum expected cost of transportation as objective and ILS factors as constraints. Finally, a numerical case is studied to prove the validity of the model by using the genetic algorithm. Results show that depot location obtained by this model can guarantee the effectiveness and capability of ILS well.展开更多
Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to si...Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.展开更多
Spare parts are critical to scheduled maintenance and fault repair, and can directly affect the readiness and combat capability of equipment. Equipmentrs capacity of carrying spares is influenced by its storage space ...Spare parts are critical to scheduled maintenance and fault repair, and can directly affect the readiness and combat capability of equipment. Equipmentrs capacity of carrying spares is influenced by its storage space and scales, so it is necessary to consider economic factors, e.g. spares cost, as well as non-economic ones, such as spares volume, mass and scale, when optimizing spares configuration. Aiming at this problem, the optimization model based on multi-constraints for carrying spares is built by METRIC theory and system analysis. Through the introduction of Lagrange factors, the spares cost is transformed to shadow price, and the optimization method for carrying spares and the dynamic adjustment policy of Lagrange factors are proposed. The result of a given example is analyzed, and demonstrates that the proposed model can be optimized with all constraints, and the research can provide a new way for carrying spares optimization.展开更多
Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays...Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.展开更多
Allocation of fleet's spare parts is rarely studied due to its complexity. However, this task is extremely important because the warship's service level highly relies on the maintenance logistics' level. I...Allocation of fleet's spare parts is rarely studied due to its complexity. However, this task is extremely important because the warship's service level highly relies on the maintenance logistics' level. In this study, the readiness ratio is proposed as a critical index in measuring the system's reliability. A well-established mathematical model adopting the optimization method of spare part allocation is also introduced. The objective is to minimize the number of each spare part while satisfying the fleet's system reliability. The fault tree analysis(FTA) is applied to analyze the system's failure logic and stratify the units on ship. As a result, the strategy of spare part sharing can be introduced in detail. The solution algorithm is developed, and the simulation experiments to obtain the key parameters are conducted. The proposed model and algorithm are applied to an actual fleet of two warships, and results show that the method above is feasible and can be directly applied into practice.展开更多
This paper presents a joint optimization policy of preventive maintenance(PM)and spare ordering for single-unit systems,which deteriorate subject to the delay-time concept with three deterioration stages.PM activities...This paper presents a joint optimization policy of preventive maintenance(PM)and spare ordering for single-unit systems,which deteriorate subject to the delay-time concept with three deterioration stages.PM activities that combine a non-periodic inspection scheme with age-replacement are implemented.When the system is detected to be in the minor defective stage by an inspection for the first time,place an order and shorten the inspection interval.If the system has deteriorated to a severe defective stage,it is either repaired imperfectly or replaced by a new spare.However,an immediate replacement is required once the system fails,the maximal number of imperfect maintenance(IPM)is satisfied or its age reaches to a pre-specified threshold.In consideration of the spare’s availability as needed,there are three types of decisions,i.e.,an immediate or a delayed replacement by a regular ordered spare,an immediate replacement by an expedited ordered spare with a relative higher cost.Then,some mutually independent and exclusive renewal events at the end of a renewal cycle are discussed,and the optimization model of such a joint policy is further developed by minimizing the long-run expected cost rate to find the optimal inspection and age-replacement intervals,and the maximum number of IPM.A Monte-Carlo based integration method is also designed to solve the proposed model.Finally,a numerical example is given to illustrate the proposed joint optimization policy and the performance of the Monte-Carlo based integration method.展开更多
This paper proposes a joint inspection-based maintenance and spare ordering optimization policy that considers the problem of integrated inspection,preventive maintenance,spare ordering,and quality control for a four-...This paper proposes a joint inspection-based maintenance and spare ordering optimization policy that considers the problem of integrated inspection,preventive maintenance,spare ordering,and quality control for a four-state single-unit manufacturing system.When an inspection detects a minor defect,a second phase inspection is initiated and a regular order is placed.Product quality begins to deteriorate when the system undergoes a severe defect.To counter this,an advanced replacement of the minor defective system is carried out at the Jth second phase inspection.If a severe defect is recognized prior to the Jth inspection,or if system failure occurs,preventive or corrective replacement is executed.The timeliness of replacement depends on the availability of spare.We adopt two modes of ordering:a regular order and an emergency order.Meanwhile,a threshold level is introduced to determine whether an emergency order is preferred even when the regular order is already ordered but has not yet arrived.The optimal joint inspection-based maintenance and spare ordering policy is formulated by minimizing the expected cost per unit time.A simulation algorithm is proposed to obtain the optimal two-phase inspection interval,threshold level and advanced replacement interval.Results from several numerical examples demonstrate that,in terms of the expected cost per unit time,our proposed model is superior to some existing models.展开更多
Characters of head of low head pump station and the pump shaft power areanalyzed. Influence of each single factor on pump shaft power is expressed as change of specificshaft power. (non-dimensional) and the probabilit...Characters of head of low head pump station and the pump shaft power areanalyzed. Influence of each single factor on pump shaft power is expressed as change of specificshaft power. (non-dimensional) and the probability density function is determined. Influences ofmultiple factors on pump shaft power are analyzed. Method of calculating none over-loadedprobability of motor by integration by successive reductions is put forward and then relationbetween power spare coefficient and none over-loaded reliability of electric motor is established.Influences of all factors on pump shaft power being considered completely; power spare coefficientsof motor are calculated in three kinds of heads (changing and unchanging), two kinds of dirty-outconditions. Electrical motor power spare coefficients should be chosen as 1.20 approx 1.44, 1.11approx 1.19, 1.09 approx.14 respectively when pump heads are 4, 7, 9.5 m. The results mean much toreasonable choose of electrical motors in large pump stations, increasing reliability of pump unitsand saving equipment investment.展开更多
基金National High-Technology Research and Development Program of China(863 Program)(No.2013AA040203)
文摘Cold spare is the most common configuration amongst the three types of configuration for systems used on board and for power generation systems. A new approach to calculate the unavailability of systems composed of identical spares in cold spare configuration was proposed in this study. Instead of using the spare gate of dynamic fault tree( DFT) and the Markov analysis,AND gate of static fault tree used for calculating the unavailability of cold spare systems was proposed in this paper. By using this approach,unavailability of identical cold spare systems composed of nonrepairable spare components can be calculated exactly and systems composed of both repairable and nonreparable identical spare components can be estimated without building large Markov state diagram.
文摘Based on an investigation on the current situation of SPM in some enterprises, this paper presents the common probletns and poor fields existing in SPM in enterprise; analyzes the reasons which resulted in the situation, and then puts forward some feasible measures to improve it. Lastly, some fields that should be paid more attention in SPM are provided.
基金co-supported by the General Armament Department Pre-research Foundation of China (Nos. 51304010206, 51327 020105)
文摘Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost （LCC）. With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and con-sumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the （s-1, s） and （R, Q） inventory policy, the spares resup-ply model is established under the batch ordering policy based on inventory state, and the optimi-zation analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets：one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation;therefore, the model＇s correctness, method＇s validity as well as optimization project＇s rationality are proved to a certain extent.
基金supported by grants from the National Natural Science Foundation of China(31171070,81171060,81501070and 81571079)
文摘Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- anism. Here, we determined that spared nerve injury （SNI） increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia （DRG） neurons and satellite glial cells. SNI also induced long- lasting upregulation of CXCL12 and CXCR4 in the ipsi- lateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNI- induced a sustained increase in TNF-α expression in the DRG and spinal cord. Intraperitoneal injection （i.p.） of the TNF-α synthesis inhibitor thalidomide reduced the SNI-in- duced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection （i.t.） of the CXCR4 antagonist AMD3100, both 30 rain before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. admin- istration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the acti- vation of ERK in the spinal cord. The mechanical hyper- sensitivity induced in nai＇ve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-α might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL 12/CXCR4 sig- naling via ERK activation contributes to the development and maintenance of neuropathic pain.
基金supported by the National Natural Science Foundation of China(6110413261304148)
文摘Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair level focuses on economic analysis models which are used to optimize costs and rarely considers the maintenance time required by the implementation of the maintenance program. In fact, as to the system requiring high mission complete success, the maintenance time is an important factor which has a great influence on the availability of equipment systems. Considering the relationship between the maintenance time and the spares stocks level, it is obvious that there are contradictions between the maintenance time and the cost. In order to balance these two factors, it is necessary to build an optimization LORA model. To this end, the maintenance time representing performance characteristic is introduced, and on the basis of spares stocks which is traditionally regarded as a decision variable, a decision variable of repair level is added, and a multi-echelon multiindenture（MEMI） optimization LORA model is built which takes the best cost-effectiveness ratio as the criterion, the expected number of backorder（EBO） as the objective function and the cost as the constraint. Besides, the paper designs a convex programming algorithm of multi-variable for the optimization model, provides solutions to the non-convex objective function and methods for improving the efficiency of the algorithm. The method provided in this paper is proved to be credible and effective according to the numerical example and the simulation result.
基金supported by the National Defense Pre-research Project in 13th Five-Year(41404050502)the National Defense Science and Technology Fund of the Central Military Commission(2101140)
文摘In order to optimize the spares configuration project at different stages during the life cycle, the factor of time is considered to relax the assumption of the spares steady demand in multi-echelon technique for recoverable item control (METRIC) theory. According to the method of systems analysis, the dynamic palm theorem is introduced to establish the prediction model of the spares demand rate, and its main influence factors are analyzed, based on which, the spares support effectiveness evaluation index system is studied, and the system optimization-oriented spares dynamic configuration method for multi-echelon multi-indenture system is proposed. Through the analysis of the optimization algorithm, the layered marginal algorithm is designed to improve the model calculation efficiency. In a given example, the multi-stage spares configuration project during its life cycle is gotten, the research result conforms to the actual status, and it can provide a new way for the spares dynamic optimization.
基金supported by the National Natural Science Foundation of China (60904002 70971132)
文摘A collaborative optimization model for maintenance and spare ordering of a single-unit degrading system is proposed in this paper based on the continuous detection. A gamma distribution is used to model the material degradation. The degrading decrement after the imperfect maintenance action is assumed as a random variable normal distribution. This model aims to ob- tain the optimal maintenance policy and spare ordering point with the expected cost rate within system lifecycle as the optimization objective. The rationality and feasibility of the model are proved through a numerical example.
基金supported by the National Defense Pre-research Project in the 13th Five-Year(41404050502)the National Defense Science and Technology Fund of the Central Military Commission(2101140)
文摘Redundancy is a common structure for warship system,and it is an effective way to improve the reliability of the system.In this paper, warship system is taken as the object of study,based on the system reliability equivalence principle, a spares demand rate calculation method for redundant system is proposed through structure transformation. According to the system analysis method, the general modeling data structure of spares support echelon and system indenture is established, and the mission success probability is taken as the optimization target to build the dynamic optimization model of carrying spares during the process of multi-phase. By introducing the Lagrange multiplier, the spares weight, volume and cost are transformed to the single target of the spares total scale, and the initial Lagrange factors and its dynamic adjustment policy is proposed. In a given example, the main influence factors of the carrying spares project are analyzed, and the study results are in accordance with the reality, which can provide a new approach to mission-oriented carrying spares optimization for the redundant system.
基金supported by the Fundamental Research Funds for the Central Universities(NS2015072)
文摘With the wide application of condition based maintenance(CBM) in aircraft maintenance practice, the joint optimization of maintenance and inventory management, which can take full advantage of CBM and reduce the aircraft operational cost, is receiving increasing attention. In order to optimize the inspection interval, maintenance decision and spare provisioning together for aircraft deteriorating parts, firstly, a joint inventory management strategy is presented, then, a joint optimization of maintenance inspection and spare provisioning for aircraft parts subject to the Wiener degradation process is proposed based on the strategy.Secondly, a combination of the genetic algorithm(GA) and the Monte Carol method is developed to minimize the total cost rate.Finally, a case study is conducted and the proposed joint optimization model is compared with the existing optimization model and the airline real case. The results demonstrate that the proposed model is more beneficial and effective. In addition, the sensitivity analysis of the proposed model shows that the lead time has higher influence on the optimal results than the urgent order cost and the corrective maintenance cost, which is consistent with the actual situation of aircraft maintenance practices and inventory management.
基金supported by grants from the National Natural Science Foundation of China (31771188 and 31471027)the Science and Technology Commission of Shanghai Municipality, China (13DJ1400302)
文摘Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brushevoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1(Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury(SNI).Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in na¨?ve but also in ML133-pretreated mice. In contrast, bicuculline, a GABAAreceptor antagonist, induced only punctate, but not dynamic,allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents(gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration oracute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively.In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.
基金partially supported by the MBRS-RISE Program(R25 GM061838)MBRS-SCORE(SO6-GM08224)+2 种基金COBRE(5P20-GM103642)SNRP(NS39405)RCMI(8G12MD007600)
文摘The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.
基金supported by the Science Challenge Project(TZ2018007)the National Natural Science Foundation of China(71671009+2 种基金 61871013 61573041 61573043)
文摘In equipment integrated logistics support(ILS), the supply capability of spare parts is a significant factor. There are lots of depots in the traditional support system, which makes too many redundant spare parts and causes high cost of support. Meanwhile,the inconsistency among depots makes it difficult to manage spare parts. With the development of information technology and transportation, the supply network has become more efficient. In order to further improve the efficiency of supply-support work and the availability of the equipment system, building a system of one centralized depot with multiple depots becomes an appropriate way.In this case, location selection of the depots including centralized depots and multiple depots becomes a top priority in the support system. This paper will focus on the location selection problem of centralized depots considering ILS factors. Unlike the common location selection problem, depots in ILS require a higher service level. Therefore, it becomes desperately necessary to take the high requirement of the mission into account while determining location of depots. Based on this, we raise an optimal depot location model. First, the expected transportation cost is calculated.Next, factors in ILS such as response time, availability and fill rate are analyzed for evaluating positions of open depots. Then, an optimization model of depot location is developed with the minimum expected cost of transportation as objective and ILS factors as constraints. Finally, a numerical case is studied to prove the validity of the model by using the genetic algorithm. Results show that depot location obtained by this model can guarantee the effectiveness and capability of ILS well.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2015RIDIAIA01059432)
文摘Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.
基金supported in part by the General Armament Department Pre-research Foundation in 12th FiveYear(No.51304010206)the National Defense Pre-research Project in 13th Five-Year (No.41404050502)
文摘Spare parts are critical to scheduled maintenance and fault repair, and can directly affect the readiness and combat capability of equipment. Equipmentrs capacity of carrying spares is influenced by its storage space and scales, so it is necessary to consider economic factors, e.g. spares cost, as well as non-economic ones, such as spares volume, mass and scale, when optimizing spares configuration. Aiming at this problem, the optimization model based on multi-constraints for carrying spares is built by METRIC theory and system analysis. Through the introduction of Lagrange factors, the spares cost is transformed to shadow price, and the optimization method for carrying spares and the dynamic adjustment policy of Lagrange factors are proposed. The result of a given example is analyzed, and demonstrates that the proposed model can be optimized with all constraints, and the research can provide a new way for carrying spares optimization.
基金National Natural Science Foundation of China,No.819 73305 (to ZQ)Science and Technology Planning Project of Guangzhou of China,No.20190401 0487 (to ZQ)+1 种基金Natural Science Foundation of Guangdong Province,China,No.2021A1515010897 (to TT)Discipline Construction Fund of Cen tral Peoples Hospital of Zhanjiang,Nos.2020A01 (to TT) and 2020A02 (to TT)。
文摘Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.
文摘Allocation of fleet's spare parts is rarely studied due to its complexity. However, this task is extremely important because the warship's service level highly relies on the maintenance logistics' level. In this study, the readiness ratio is proposed as a critical index in measuring the system's reliability. A well-established mathematical model adopting the optimization method of spare part allocation is also introduced. The objective is to minimize the number of each spare part while satisfying the fleet's system reliability. The fault tree analysis(FTA) is applied to analyze the system's failure logic and stratify the units on ship. As a result, the strategy of spare part sharing can be introduced in detail. The solution algorithm is developed, and the simulation experiments to obtain the key parameters are conducted. The proposed model and algorithm are applied to an actual fleet of two warships, and results show that the method above is feasible and can be directly applied into practice.
基金supported by the Naitonal Natural Science Foundation of China(71701038)China Ministry of Education Humanities and Social Sciences Research Youth Fund Project(16YJC630174)+2 种基金the Natural Science Foundation of Hebei Province(G2019501074)the Fundamental Research Funds for the Central Universities(N2123019)the Postgraduate Funding Project of PLA(JY2020B085).
文摘This paper presents a joint optimization policy of preventive maintenance(PM)and spare ordering for single-unit systems,which deteriorate subject to the delay-time concept with three deterioration stages.PM activities that combine a non-periodic inspection scheme with age-replacement are implemented.When the system is detected to be in the minor defective stage by an inspection for the first time,place an order and shorten the inspection interval.If the system has deteriorated to a severe defective stage,it is either repaired imperfectly or replaced by a new spare.However,an immediate replacement is required once the system fails,the maximal number of imperfect maintenance(IPM)is satisfied or its age reaches to a pre-specified threshold.In consideration of the spare’s availability as needed,there are three types of decisions,i.e.,an immediate or a delayed replacement by a regular ordered spare,an immediate replacement by an expedited ordered spare with a relative higher cost.Then,some mutually independent and exclusive renewal events at the end of a renewal cycle are discussed,and the optimization model of such a joint policy is further developed by minimizing the long-run expected cost rate to find the optimal inspection and age-replacement intervals,and the maximum number of IPM.A Monte-Carlo based integration method is also designed to solve the proposed model.Finally,a numerical example is given to illustrate the proposed joint optimization policy and the performance of the Monte-Carlo based integration method.
基金This work was supported by the National Natural Science Foundation of China(71471015)the Social Science Fund Base Project of Beijing(19JDGLA001).
文摘This paper proposes a joint inspection-based maintenance and spare ordering optimization policy that considers the problem of integrated inspection,preventive maintenance,spare ordering,and quality control for a four-state single-unit manufacturing system.When an inspection detects a minor defect,a second phase inspection is initiated and a regular order is placed.Product quality begins to deteriorate when the system undergoes a severe defect.To counter this,an advanced replacement of the minor defective system is carried out at the Jth second phase inspection.If a severe defect is recognized prior to the Jth inspection,or if system failure occurs,preventive or corrective replacement is executed.The timeliness of replacement depends on the availability of spare.We adopt two modes of ordering:a regular order and an emergency order.Meanwhile,a threshold level is introduced to determine whether an emergency order is preferred even when the regular order is already ordered but has not yet arrived.The optimal joint inspection-based maintenance and spare ordering policy is formulated by minimizing the expected cost per unit time.A simulation algorithm is proposed to obtain the optimal two-phase inspection interval,threshold level and advanced replacement interval.Results from several numerical examples demonstrate that,in terms of the expected cost per unit time,our proposed model is superior to some existing models.
文摘Characters of head of low head pump station and the pump shaft power areanalyzed. Influence of each single factor on pump shaft power is expressed as change of specificshaft power. (non-dimensional) and the probability density function is determined. Influences ofmultiple factors on pump shaft power are analyzed. Method of calculating none over-loadedprobability of motor by integration by successive reductions is put forward and then relationbetween power spare coefficient and none over-loaded reliability of electric motor is established.Influences of all factors on pump shaft power being considered completely; power spare coefficientsof motor are calculated in three kinds of heads (changing and unchanging), two kinds of dirty-outconditions. Electrical motor power spare coefficients should be chosen as 1.20 approx 1.44, 1.11approx 1.19, 1.09 approx.14 respectively when pump heads are 4, 7, 9.5 m. The results mean much toreasonable choose of electrical motors in large pump stations, increasing reliability of pump unitsand saving equipment investment.
