Due to the impact of source-load prediction power errors and uncertainties,the actual operation of the park will have a wide range of fluctuations compared with the expected state,resulting in its inability to achieve...Due to the impact of source-load prediction power errors and uncertainties,the actual operation of the park will have a wide range of fluctuations compared with the expected state,resulting in its inability to achieve the expected economy.This paper constructs an operating simulation model of the park power grid operation considering demand response and proposes a multi-time scale operating simulation method that combines day-ahead optimization and model predictive control(MPC).In the day-ahead stage,an operating simulation plan that comprehensively considers the user’s side comfort and operating costs is proposed with a long-term time scale of 15 min.In order to cope with power fluctuations of photovoltaic,wind turbine and conventional load,MPC is used to track and roll correct the day-ahead operating simulation plan in the intra-day stage to meet the actual operating operation status of the park.Finally,the validity and economy of the operating simulation strategy are verified through the analysis of arithmetic examples.展开更多
Building emission reduction is an important way to achieve China’s carbon peaking and carbon neutrality goals.Aiming at the problem of low carbon economic operation of a photovoltaic energy storage building system,a ...Building emission reduction is an important way to achieve China’s carbon peaking and carbon neutrality goals.Aiming at the problem of low carbon economic operation of a photovoltaic energy storage building system,a multi-time scale optimal scheduling strategy based on model predictive control(MPC)is proposed under the consideration of load optimization.First,load optimization is achieved by controlling the charging time of electric vehicles as well as adjusting the air conditioning operation temperature,and the photovoltaic energy storage building system model is constructed to propose a day-ahead scheduling strategy with the lowest daily operation cost.Second,considering inter-day to intra-day source-load prediction error,an intraday rolling optimal scheduling strategy based on MPC is proposed that dynamically corrects the day-ahead dispatch results to stabilize system power fluctuations and promote photovoltaic consumption.Finally,taking an office building on a summer work day as an example,the effectiveness of the proposed scheduling strategy is verified.The results of the example show that the strategy reduces the total operating cost of the photovoltaic energy storage building system by 17.11%,improves the carbon emission reduction by 7.99%,and the photovoltaic consumption rate reaches 98.57%,improving the system’s low-carbon and economic performance.展开更多
This paper introduces a novel multi-tiered defense architecture to protect language models from adversarial prompt attacks. We construct adversarial prompts using strategies like role emulation and manipulative assist...This paper introduces a novel multi-tiered defense architecture to protect language models from adversarial prompt attacks. We construct adversarial prompts using strategies like role emulation and manipulative assistance to simulate real threats. We introduce a comprehensive, multi-tiered defense framework named GUARDIAN (Guardrails for Upholding Ethics in Language Models) comprising a system prompt filter, pre-processing filter leveraging a toxic classifier and ethical prompt generator, and pre-display filter using the model itself for output screening. Extensive testing on Meta’s Llama-2 model demonstrates the capability to block 100% of attack prompts. The approach also auto-suggests safer prompt alternatives, thereby bolstering language model security. Quantitatively evaluated defense layers and an ethical substitution mechanism represent key innovations to counter sophisticated attacks. The integrated methodology not only fortifies smaller LLMs against emerging cyber threats but also guides the broader application of LLMs in a secure and ethical manner.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these me...To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.展开更多
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
Expenditure on wells constitute a significant part of the operational costs for a petroleum enterprise, where most of the cost results from drilling. This has prompted drilling departments to continuously look for wa...Expenditure on wells constitute a significant part of the operational costs for a petroleum enterprise, where most of the cost results from drilling. This has prompted drilling departments to continuously look for ways to reduce their drilling costs and be as efficient as possible. A system called the Drilling Comprehensive Information Management and Application System (DCIMAS) is developed and presented here, with an aim at collecting, storing and making full use of the valuable well data and information relating to all drilling activities and operations. The DCIMAS comprises three main parts, including a data collection and transmission system, a data warehouse (DW) management system, and an integrated platform of core applications. With the support of the application platform, the DW management system is introduced, whereby the operation data are captured at well sites and transmitted electronically to a data warehouse via transmission equipment and ETL (extract, transformation and load) tools. With the high quality of the data guaranteed, our central task is to make the best use of the operation data and information for drilling analysis and to provide further information to guide later production stages. Applications have been developed and integrated on a uniform platform to interface directly with different layers of the multi-tier DW. Now, engineers in every department spend less time on data handling and more time on applying technology in their real work with the system.展开更多
安全生产事故往往由多组织交互、多因素耦合造成,事故原因涉及多个组织。为预防和遏制多组织生产安全事故的发生,基于系统理论事故建模与过程模型(Systems-Theory Accident Modeling and Process,STAMP)、24Model,构建一种用于多组织事...安全生产事故往往由多组织交互、多因素耦合造成,事故原因涉及多个组织。为预防和遏制多组织生产安全事故的发生,基于系统理论事故建模与过程模型(Systems-Theory Accident Modeling and Process,STAMP)、24Model,构建一种用于多组织事故分析的方法,并以青岛石油爆炸事故为例进行事故原因分析。结果显示:STAMP-24Model可以分组织,分层次且有效、全面、详细地分析涉及多个组织的事故原因,探究多组织之间的交互关系;对事故进行动态演化分析,可得到各组织不安全动作耦合关系与形成的事故失效链及管控失效路径,进而为预防多组织事故提供思路和参考。展开更多
A seismic assessment of two multi-tier pagodas by numerical analysis is presented herein.The Changu Narayan temple and the Kumbeshwar temple in Nepal are used as the case studies.Both pagodas are built of brick masonr...A seismic assessment of two multi-tier pagodas by numerical analysis is presented herein.The Changu Narayan temple and the Kumbeshwar temple in Nepal are used as the case studies.Both pagodas are built of brick masonry in earthen mortar,with timber columns and crossbeams.The Changu Narayan temple is a two-tier pagoda,and was seriously damaged during the 2015 Gorkha earthquake.The Kumbeshwar temple is a five-tier pagoda,and its top-tier collapsed due to the Gorkha earthquake.A seismic assessment was carried out using finite element(FE)analysis.The FE models were prepared,and dynamic identification tests and penetrometer tests were conducted.Pushover analysis and nonlinear dynamic analysis were performed as part of the seismic assessment.The main shock of the 2015 Gorkha earthquake was considered as the input accelerograms.The behavior between the two pagodas was compared with the collapse mechanisms and damage patterns observed in the actual structures.The comparison suggested common structural features of multi-tier pagodas.This study is dedicated to providing a better understanding of the seismic behavior of multi-tier pagoda-type structures and provides suggestions for their effective analysis.展开更多
The current mathematical models for the storage assignment problem are generally established based on the traveling salesman problem(TSP),which has been widely applied in the conventional automated storage and retri...The current mathematical models for the storage assignment problem are generally established based on the traveling salesman problem(TSP),which has been widely applied in the conventional automated storage and retrieval system(AS/RS).However,the previous mathematical models in conventional AS/RS do not match multi-tier shuttle warehousing systems(MSWS) because the characteristics of parallel retrieval in multiple tiers and progressive vertical movement destroy the foundation of TSP.In this study,a two-stage open queuing network model in which shuttles and a lift are regarded as servers at different stages is proposed to analyze system performance in the terms of shuttle waiting period(SWP) and lift idle period(LIP) during transaction cycle time.A mean arrival time difference matrix for pairwise stock keeping units(SKUs) is presented to determine the mean waiting time and queue length to optimize the storage assignment problem on the basis of SKU correlation.The decomposition method is applied to analyze the interactions among outbound task time,SWP,and LIP.The ant colony clustering algorithm is designed to determine storage partitions using clustering items.In addition,goods are assigned for storage according to the rearranging permutation and the combination of storage partitions in a 2D plane.This combination is derived based on the analysis results of the queuing network model and on three basic principles.The storage assignment method and its entire optimization algorithm method as applied in a MSWS are verified through a practical engineering project conducted in the tobacco industry.The applying results show that the total SWP and LIP can be reduced effectively to improve the utilization rates of all devices and to increase the throughput of the distribution center.展开更多
Complex multi-tier applications deployed in cloud computing environments can experience rapid changes in their workloads. To ensure market readiness of such applications, adequate resources need to be provisioned so t...Complex multi-tier applications deployed in cloud computing environments can experience rapid changes in their workloads. To ensure market readiness of such applications, adequate resources need to be provisioned so that the applications can meet the demands of specified workload levels and at the same time ensure that service level agreements are met. Multi-tier cloud applications can have complex deployment configurations with load balancers, web servers, application servers and database servers. Complex dependencies may exist between servers in various tiers. To support provisioning and capacity planning decisions, performance testing approaches with synthetic workloads are used. Accuracy of a performance testing approach is determined by how closely the generated synthetic workloads mimic the realistic workloads. Since multi-tier applications can have varied deployment configurations and characteristic workloads, there is a need for a generic performance testing methodology that allows accurately modeling the performance of applications. We propose a methodology for performance testing of complex multi-tier applications. The workloads of multi-tier cloud applications are captured in two different models-benchmark application and workload models. An architecture model captures the deployment configurations of multi-tier applications. We propose a rapid deployment prototyping methodology that can help in choosing the best and most cost effective deployments for multi-tier applications that meet the specified performance requirements. We also describe a system bottleneck detection approach based on experimental evaluation of multi-tier applications.展开更多
基金supported by the Science and Technology Project of State Grid Shanxi Electric Power Research Institute:Research on Data-Driven New Power System Operation Simulation and Multi Agent Control Strategy(52053022000F).
文摘Due to the impact of source-load prediction power errors and uncertainties,the actual operation of the park will have a wide range of fluctuations compared with the expected state,resulting in its inability to achieve the expected economy.This paper constructs an operating simulation model of the park power grid operation considering demand response and proposes a multi-time scale operating simulation method that combines day-ahead optimization and model predictive control(MPC).In the day-ahead stage,an operating simulation plan that comprehensively considers the user’s side comfort and operating costs is proposed with a long-term time scale of 15 min.In order to cope with power fluctuations of photovoltaic,wind turbine and conventional load,MPC is used to track and roll correct the day-ahead operating simulation plan in the intra-day stage to meet the actual operating operation status of the park.Finally,the validity and economy of the operating simulation strategy are verified through the analysis of arithmetic examples.
文摘Building emission reduction is an important way to achieve China’s carbon peaking and carbon neutrality goals.Aiming at the problem of low carbon economic operation of a photovoltaic energy storage building system,a multi-time scale optimal scheduling strategy based on model predictive control(MPC)is proposed under the consideration of load optimization.First,load optimization is achieved by controlling the charging time of electric vehicles as well as adjusting the air conditioning operation temperature,and the photovoltaic energy storage building system model is constructed to propose a day-ahead scheduling strategy with the lowest daily operation cost.Second,considering inter-day to intra-day source-load prediction error,an intraday rolling optimal scheduling strategy based on MPC is proposed that dynamically corrects the day-ahead dispatch results to stabilize system power fluctuations and promote photovoltaic consumption.Finally,taking an office building on a summer work day as an example,the effectiveness of the proposed scheduling strategy is verified.The results of the example show that the strategy reduces the total operating cost of the photovoltaic energy storage building system by 17.11%,improves the carbon emission reduction by 7.99%,and the photovoltaic consumption rate reaches 98.57%,improving the system’s low-carbon and economic performance.
文摘This paper introduces a novel multi-tiered defense architecture to protect language models from adversarial prompt attacks. We construct adversarial prompts using strategies like role emulation and manipulative assistance to simulate real threats. We introduce a comprehensive, multi-tiered defense framework named GUARDIAN (Guardrails for Upholding Ethics in Language Models) comprising a system prompt filter, pre-processing filter leveraging a toxic classifier and ethical prompt generator, and pre-display filter using the model itself for output screening. Extensive testing on Meta’s Llama-2 model demonstrates the capability to block 100% of attack prompts. The approach also auto-suggests safer prompt alternatives, thereby bolstering language model security. Quantitatively evaluated defense layers and an ethical substitution mechanism represent key innovations to counter sophisticated attacks. The integrated methodology not only fortifies smaller LLMs against emerging cyber threats but also guides the broader application of LLMs in a secure and ethical manner.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
基金supported by University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
文摘Expenditure on wells constitute a significant part of the operational costs for a petroleum enterprise, where most of the cost results from drilling. This has prompted drilling departments to continuously look for ways to reduce their drilling costs and be as efficient as possible. A system called the Drilling Comprehensive Information Management and Application System (DCIMAS) is developed and presented here, with an aim at collecting, storing and making full use of the valuable well data and information relating to all drilling activities and operations. The DCIMAS comprises three main parts, including a data collection and transmission system, a data warehouse (DW) management system, and an integrated platform of core applications. With the support of the application platform, the DW management system is introduced, whereby the operation data are captured at well sites and transmitted electronically to a data warehouse via transmission equipment and ETL (extract, transformation and load) tools. With the high quality of the data guaranteed, our central task is to make the best use of the operation data and information for drilling analysis and to provide further information to guide later production stages. Applications have been developed and integrated on a uniform platform to interface directly with different layers of the multi-tier DW. Now, engineers in every department spend less time on data handling and more time on applying technology in their real work with the system.
文摘安全生产事故往往由多组织交互、多因素耦合造成,事故原因涉及多个组织。为预防和遏制多组织生产安全事故的发生,基于系统理论事故建模与过程模型(Systems-Theory Accident Modeling and Process,STAMP)、24Model,构建一种用于多组织事故分析的方法,并以青岛石油爆炸事故为例进行事故原因分析。结果显示:STAMP-24Model可以分组织,分层次且有效、全面、详细地分析涉及多个组织的事故原因,探究多组织之间的交互关系;对事故进行动态演化分析,可得到各组织不安全动作耦合关系与形成的事故失效链及管控失效路径,进而为预防多组织事故提供思路和参考。
基金Funding of Grant-in-Aid for Scientific Research(A)Provided by the Japan Society for the Promotion of the Science under Grant No.16H01825。
文摘A seismic assessment of two multi-tier pagodas by numerical analysis is presented herein.The Changu Narayan temple and the Kumbeshwar temple in Nepal are used as the case studies.Both pagodas are built of brick masonry in earthen mortar,with timber columns and crossbeams.The Changu Narayan temple is a two-tier pagoda,and was seriously damaged during the 2015 Gorkha earthquake.The Kumbeshwar temple is a five-tier pagoda,and its top-tier collapsed due to the Gorkha earthquake.A seismic assessment was carried out using finite element(FE)analysis.The FE models were prepared,and dynamic identification tests and penetrometer tests were conducted.Pushover analysis and nonlinear dynamic analysis were performed as part of the seismic assessment.The main shock of the 2015 Gorkha earthquake was considered as the input accelerograms.The behavior between the two pagodas was compared with the collapse mechanisms and damage patterns observed in the actual structures.The comparison suggested common structural features of multi-tier pagodas.This study is dedicated to providing a better understanding of the seismic behavior of multi-tier pagoda-type structures and provides suggestions for their effective analysis.
基金Supported by National Natural Science Foundation of China(Grant No.661403234)Shandong Provincial Science and Techhnology Development Plan of China(Grant No.2014GGX106009)
文摘The current mathematical models for the storage assignment problem are generally established based on the traveling salesman problem(TSP),which has been widely applied in the conventional automated storage and retrieval system(AS/RS).However,the previous mathematical models in conventional AS/RS do not match multi-tier shuttle warehousing systems(MSWS) because the characteristics of parallel retrieval in multiple tiers and progressive vertical movement destroy the foundation of TSP.In this study,a two-stage open queuing network model in which shuttles and a lift are regarded as servers at different stages is proposed to analyze system performance in the terms of shuttle waiting period(SWP) and lift idle period(LIP) during transaction cycle time.A mean arrival time difference matrix for pairwise stock keeping units(SKUs) is presented to determine the mean waiting time and queue length to optimize the storage assignment problem on the basis of SKU correlation.The decomposition method is applied to analyze the interactions among outbound task time,SWP,and LIP.The ant colony clustering algorithm is designed to determine storage partitions using clustering items.In addition,goods are assigned for storage according to the rearranging permutation and the combination of storage partitions in a 2D plane.This combination is derived based on the analysis results of the queuing network model and on three basic principles.The storage assignment method and its entire optimization algorithm method as applied in a MSWS are verified through a practical engineering project conducted in the tobacco industry.The applying results show that the total SWP and LIP can be reduced effectively to improve the utilization rates of all devices and to increase the throughput of the distribution center.
文摘Complex multi-tier applications deployed in cloud computing environments can experience rapid changes in their workloads. To ensure market readiness of such applications, adequate resources need to be provisioned so that the applications can meet the demands of specified workload levels and at the same time ensure that service level agreements are met. Multi-tier cloud applications can have complex deployment configurations with load balancers, web servers, application servers and database servers. Complex dependencies may exist between servers in various tiers. To support provisioning and capacity planning decisions, performance testing approaches with synthetic workloads are used. Accuracy of a performance testing approach is determined by how closely the generated synthetic workloads mimic the realistic workloads. Since multi-tier applications can have varied deployment configurations and characteristic workloads, there is a need for a generic performance testing methodology that allows accurately modeling the performance of applications. We propose a methodology for performance testing of complex multi-tier applications. The workloads of multi-tier cloud applications are captured in two different models-benchmark application and workload models. An architecture model captures the deployment configurations of multi-tier applications. We propose a rapid deployment prototyping methodology that can help in choosing the best and most cost effective deployments for multi-tier applications that meet the specified performance requirements. We also describe a system bottleneck detection approach based on experimental evaluation of multi-tier applications.