In this paper, a life-cycle model with retirement is set up to study how an individual chooses the optimal retiring age on account of wage growth rate, longevity and healthy state. It is proved that there exists optim...In this paper, a life-cycle model with retirement is set up to study how an individual chooses the optimal retiring age on account of wage growth rate, longevity and healthy state. It is proved that there exists optimal retiring age under given conditions. The numerical simulations are given to show how wage growth rate, longevity and healthy state affect retiring age.展开更多
Intelligent chatbots powered by large language models(LLMs)have recently been sweeping the world,with potential for a wide variety of industrial applications.Global frontier technology companies are feverishly partici...Intelligent chatbots powered by large language models(LLMs)have recently been sweeping the world,with potential for a wide variety of industrial applications.Global frontier technology companies are feverishly participating in LLM-powered chatbot design and development,providing several alternatives beyond the famous ChatGPT.However,training,fine-tuning,and updating such intelligent chatbots consume substantial amounts of electricity,resulting in significant carbon emissions.The research and development of all intelligent LLMs and software,hardware manufacturing(e.g.,graphics processing units and supercomputers),related data/operations management,and material recycling supporting chatbot services are associated with carbon emissions to varying extents.Attention should therefore be paid to the entire life-cycle energy and carbon footprints of LLM-powered intelligent chatbots in both the present and future in order to mitigate their climate change impact.In this work,we clarify and highlight the energy consumption and carbon emission implications of eight main phases throughout the life cycle of the development of such intelligent chatbots.Based on a life-cycle and interaction analysis of these phases,we propose a system-level solution with three strategic pathways to optimize the management of this industry and mitigate the related footprints.While anticipating the enormous potential of this advanced technology and its products,we make an appeal for a rethinking of the mitigation pathways and strategies of the life-cycle energy usage and carbon emissions of the LLM-powered intelligent chatbot industry and a reshaping of their energy and environmental implications at this early stage of development.展开更多
Reinforcement corrosion is the main cause of performance deterioration of reinforced concrete(RC)structures.Limited research has been performed to investigate the life-cycle cost(LCC)of coastal bridge piers with nonun...Reinforcement corrosion is the main cause of performance deterioration of reinforced concrete(RC)structures.Limited research has been performed to investigate the life-cycle cost(LCC)of coastal bridge piers with nonuniform corrosion using different materials.In this study,a reliability-based design optimization(RBDO)procedure is improved for the design of coastal bridge piers using six groups of commonly used materials,i.e.,normal performance concrete(NPC)with black steel(BS)rebar,high strength steel(HSS)rebar,epoxy coated(EC)rebar,and stainless steel(SS)rebar(named NPC-BS,NPC-HSS,NPC-EC,and NPC-SS,respectively),NPC with BS with silane soakage on the pier surface(named NPC-Silane),and high-performance concrete(HPC)with BS rebar(named HPC-BS).First,the RBDO procedure is improved for the design optimization of coastal bridge piers,and a bridge is selected to illustrate the procedure.Then,reliability analysis of the pier designed with each group of materials is carried out to obtain the time-dependent reliability in terms of the ultimate and serviceability performances.Next,the repair time of the pier is predicted based on the time-dependent reliability indices.Finally,the time-dependent LCCs for the pier are obtained for the selection of the optimal design.展开更多
With the continuous development of urban public transportation, the harmful GHG emissions and pollutants generated by itself and the consequent issues such as the losses of residents’ health, economic value and resid...With the continuous development of urban public transportation, the harmful GHG emissions and pollutants generated by itself and the consequent issues such as the losses of residents’ health, economic value and residents’ welfare have become the focus of social attention. In order to study the impacts of promoting new energy vehicles on public transportation pollution mitigation and residents’ health benefits, this paper adopts the LEAP model to build some scenarios that fulfill different development needs to quantitatively analyze the ownership of new energy buses, the reduction of pollutants and the losses of residents’ health welfare. It is concluded that promoting new energy buses comprehensively can significantly reduce the emissions of atmospheric pollutants and the economic losses of residents’ health, but cannot fully realize the targets of greenhouse gas reduction under Life Cycle Analysis.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
In order to more effectively assess the health status of a project, the monitoring indices in a project's life cycle are divided into quality index, cost index, time index, satisfaction index, and sustainable develop...In order to more effectively assess the health status of a project, the monitoring indices in a project's life cycle are divided into quality index, cost index, time index, satisfaction index, and sustainable development index. Based on the feature of qualitative and quantitative indices combining, the PCA-PR (principal component analysis and pattern recognition) model is constructed. The model first analyzes the principal components of the life-cycle indices system constructed above, and picks up those principal component indices that can reflect the health status of a project at any time. Then the pattern recognition model is used to study these principal components, which means that the real time health status of the project can be divided into five lamps from a green lamp to a red one and the health status lamp of the project can be recognized by using the PR model and those principal components. Finally, the process is shown with a real example and a conclusion consistent with the actual situation is drawn. So the validity of the index system and the PCA-PR model can be confirmed.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
Engineering structures may be exposed to one or more extreme hazards during their life-cycles.Current structural design specifications usually treat multiple hazards separately in designing structures and there is a l...Engineering structures may be exposed to one or more extreme hazards during their life-cycles.Current structural design specifications usually treat multiple hazards separately in designing structures and there is a limited probabilistic basis on extreme load combinations.Additionally,the performance of engineering structures will be deteriorated by the aggressive environments during their service periods,such as chloride attack,concrete carbonation,and wind-induced fatigue.This study presents a probabilistic methodology to assess the time-dependent failure probability of RC bridges with chloride-induced corrosion under the multiple hazards of earthquakes and strong winds.The loss of cross-section area of reinforcements and the reduction in strength of reinforcing steel and concrete cover induced by the chloride attack are considered.Moreover,the Poisson model is employed to obtain the occurrence probabilities of the individual and concurrent earthquake and strong wind events.The convolution integral is used to determine the joint probability distribution of combined load effects under simultaneous earthquakes and strong winds.Numerical results indicate that the structural failure probability under multiple hazards increases significantly during the bridge′s life-cycle due to the chloride corrosion effect.The contribution of each hazard event on the total structural failure probability varies with time.Thus,neglecting the combined influences of multiple hazards and chloride-induced corrosion may bring erroneous predictions in failure probability estimates of RC bridges.展开更多
The quantitative determination and evaluation of rock brittleness are crucial for the estimation of excavation efficiency and the improvement of hydraulic fracturing efficiency.Therefore,a“three-stage”triaxial loadi...The quantitative determination and evaluation of rock brittleness are crucial for the estimation of excavation efficiency and the improvement of hydraulic fracturing efficiency.Therefore,a“three-stage”triaxial loading and unloading stress path is designed and proposed.Subsequently,six brittleness indices are selected.In addition,the evolution characteristics of the six brittleness indices selected are characterized based on the bedding effect and the effect of confining pressure.Then,the entropy weight method(EWM)is introduced to assign weight to the six brittleness indices,and the comprehensive brittleness index Bcis defined and evaluated.Next,the new brittleness classification standard is determined,and the brittleness differences between the two stress paths are quantified.Finally,compared with the previous evaluation methods,the rationality of the proposed comprehensive brittleness index Bcis also verified.These results indicate that the proposed brittleness index Bccan reflect the brittle characteristics of deep bedded sandstone from the perspective of the whole life-cycle evolution process.Accordingly,the method proposed seems to offer reliable evaluations of the brittleness of deep bedded sandstone in deep engineering practices,although further validation is necessary.展开更多
The development and deployment of Carbon dioxide Capture and Storage (CCS) technology is a cornerstone of the Norwegian government's climate strategy. A number of projects are currently evaluated/planned along the ...The development and deployment of Carbon dioxide Capture and Storage (CCS) technology is a cornerstone of the Norwegian government's climate strategy. A number of projects are currently evaluated/planned along the Norwegian West Coast, one at Tjeldbergodden. COe from this project will be utilized in part for enhanced oil recovery in the Halten oil field, in the Norwegian Sea. We study a potential design of such a system. A combined cycle power plant with a gross power output of 832 MW is combined with CO2 capture plant based on a post-combustion capture using amines as a solvent. The captured CO2 is used for enhanced oil recovery (EOR). We employ a hybrid life-cycle assessment (LCA) method to assess the environmental impacts of the system. The study focuses on the modifications and operations of the platform during EOR. We allocate the impacts connected to the capture of CO2 to electricity production, and the impacts connected to the transport and storage of CO2 to the oil produced. Our study shows a substantial reduction of the greenhouse gas emissions from power production by 80% to 75 g·(kW·h)^-1. It also indicates a reduction of the emissions associated with oil production per unit oil produced, mostly due to the increased oil production. Reductions are especially significant if the additional power demand due to EOR leads to power supply from the land.展开更多
During the coronavirus disease 2019 (COVID-19) emergency, many hospitals were built or renovated around the world to meet the challenges posed by the rising number of infected cases. Environmental management in the ho...During the coronavirus disease 2019 (COVID-19) emergency, many hospitals were built or renovated around the world to meet the challenges posed by the rising number of infected cases. Environmental management in the hospital life cycle is vital in preventing nosocomial infection and includes many infection control procedures. In certain urgent situations, a hospital must be completed quickly, and work process approval and supervision must therefore be accelerated. Thus, many works cannot be checked in detail. This results in a lack of work liability control and increases the difficulty of ensuring the fulfillment of key infection prevention measures. This study investigates how blockchain technology can transform the work quality inspection workflow to assist in nosocomial infection control under a fast delivery requirement. A blockchain-based life-cycle environmental management framework is proposed to track the fulfillment of crucial infection control measures in the design, construction, and operation stages of hospitals. The proposed framework allows for work quality checking after the work is completed, when some work cannot be checked on time. Illustrative use cases are selected to demonstrate the capabilities of the developed solution. This study provides new insights into applying blockchain technology to address the challenge of environmental management brought by rapid delivery requirements.展开更多
As the construction sector is a major energy consumer and thus a significant contributor of CO_2 emissions in China,it is important to consider carbon reduction in this industry.This study analyzed six life-cycle stag...As the construction sector is a major energy consumer and thus a significant contributor of CO_2 emissions in China,it is important to consider carbon reduction in this industry.This study analyzed six life-cycle stages and calculated the life-cycle CO_2 emissions of the construction sector in 30 Chinese provincial jurisdictions to understand the disparity among them.Results show that building materials production was the key stage for carbon reduction in the construction sector,followed by the building operation stage.External variables,e.g.,economic growth,industrial structure,urbanization,price fluctuation,and marketization,were significantly correlated with the emission intensity of the construction sector.Specifically,economic growth exhibited an inverted U-shaped relation with CO_2 emissions per capita and per area during the period examined.Secondary industry and land urbanization were negatively correlated with CO_2 emission intensity indicators from the construction sector,whereas tertiary industry and urbanization were positively correlated.Price indices and marketization had negative effects on CO_2 emission intensity.The policy implications of our findings are that cleaner technologies should be encouraged for cement providers,and green purchasing rules for the construction sector should also be established.Pricing tools(e.g.,resource taxes)could help to adjust the demand for raw materials and energy.展开更多
基金Supported by the National Natural Science Foundation of China(71271158)
文摘In this paper, a life-cycle model with retirement is set up to study how an individual chooses the optimal retiring age on account of wage growth rate, longevity and healthy state. It is proved that there exists optimal retiring age under given conditions. The numerical simulations are given to show how wage growth rate, longevity and healthy state affect retiring age.
基金supported by the National Natural Science Foundation of China(72061127004 and 72104164)the System Science and Enterprise Development Research Center(Xq22B04)+1 种基金financial support from the Engineering and Physical Sciences Research Council(EPSRC)Programme(EP/V030515/1)financial support from the Science and Technology Support Project of Guizhou Province([2019]2839).
文摘Intelligent chatbots powered by large language models(LLMs)have recently been sweeping the world,with potential for a wide variety of industrial applications.Global frontier technology companies are feverishly participating in LLM-powered chatbot design and development,providing several alternatives beyond the famous ChatGPT.However,training,fine-tuning,and updating such intelligent chatbots consume substantial amounts of electricity,resulting in significant carbon emissions.The research and development of all intelligent LLMs and software,hardware manufacturing(e.g.,graphics processing units and supercomputers),related data/operations management,and material recycling supporting chatbot services are associated with carbon emissions to varying extents.Attention should therefore be paid to the entire life-cycle energy and carbon footprints of LLM-powered intelligent chatbots in both the present and future in order to mitigate their climate change impact.In this work,we clarify and highlight the energy consumption and carbon emission implications of eight main phases throughout the life cycle of the development of such intelligent chatbots.Based on a life-cycle and interaction analysis of these phases,we propose a system-level solution with three strategic pathways to optimize the management of this industry and mitigate the related footprints.While anticipating the enormous potential of this advanced technology and its products,we make an appeal for a rethinking of the mitigation pathways and strategies of the life-cycle energy usage and carbon emissions of the LLM-powered intelligent chatbot industry and a reshaping of their energy and environmental implications at this early stage of development.
基金National Natural Science Foundation of China under Grant Nos.51921006 and 51725801Fundamental Research Funds for the Central Universities under Grant No.FRFCU5710093320Heilongjiang Touyan Innovation Team Program。
文摘Reinforcement corrosion is the main cause of performance deterioration of reinforced concrete(RC)structures.Limited research has been performed to investigate the life-cycle cost(LCC)of coastal bridge piers with nonuniform corrosion using different materials.In this study,a reliability-based design optimization(RBDO)procedure is improved for the design of coastal bridge piers using six groups of commonly used materials,i.e.,normal performance concrete(NPC)with black steel(BS)rebar,high strength steel(HSS)rebar,epoxy coated(EC)rebar,and stainless steel(SS)rebar(named NPC-BS,NPC-HSS,NPC-EC,and NPC-SS,respectively),NPC with BS with silane soakage on the pier surface(named NPC-Silane),and high-performance concrete(HPC)with BS rebar(named HPC-BS).First,the RBDO procedure is improved for the design optimization of coastal bridge piers,and a bridge is selected to illustrate the procedure.Then,reliability analysis of the pier designed with each group of materials is carried out to obtain the time-dependent reliability in terms of the ultimate and serviceability performances.Next,the repair time of the pier is predicted based on the time-dependent reliability indices.Finally,the time-dependent LCCs for the pier are obtained for the selection of the optimal design.
文摘With the continuous development of urban public transportation, the harmful GHG emissions and pollutants generated by itself and the consequent issues such as the losses of residents’ health, economic value and residents’ welfare have become the focus of social attention. In order to study the impacts of promoting new energy vehicles on public transportation pollution mitigation and residents’ health benefits, this paper adopts the LEAP model to build some scenarios that fulfill different development needs to quantitatively analyze the ownership of new energy buses, the reduction of pollutants and the losses of residents’ health welfare. It is concluded that promoting new energy buses comprehensively can significantly reduce the emissions of atmospheric pollutants and the economic losses of residents’ health, but cannot fully realize the targets of greenhouse gas reduction under Life Cycle Analysis.
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.
基金The Social Science Fund of Hebei Province (No.200607011)the Key Science and Technology Project of Hebei Province(No.07213529)
文摘In order to more effectively assess the health status of a project, the monitoring indices in a project's life cycle are divided into quality index, cost index, time index, satisfaction index, and sustainable development index. Based on the feature of qualitative and quantitative indices combining, the PCA-PR (principal component analysis and pattern recognition) model is constructed. The model first analyzes the principal components of the life-cycle indices system constructed above, and picks up those principal component indices that can reflect the health status of a project at any time. Then the pattern recognition model is used to study these principal components, which means that the real time health status of the project can be divided into five lamps from a green lamp to a red one and the health status lamp of the project can be recognized by using the PR model and those principal components. Finally, the process is shown with a real example and a conclusion consistent with the actual situation is drawn. So the validity of the index system and the PCA-PR model can be confirmed.
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Supported by:Fundamental Research Funds for the Central Universities under Grant No.2021QN1022。
文摘Engineering structures may be exposed to one or more extreme hazards during their life-cycles.Current structural design specifications usually treat multiple hazards separately in designing structures and there is a limited probabilistic basis on extreme load combinations.Additionally,the performance of engineering structures will be deteriorated by the aggressive environments during their service periods,such as chloride attack,concrete carbonation,and wind-induced fatigue.This study presents a probabilistic methodology to assess the time-dependent failure probability of RC bridges with chloride-induced corrosion under the multiple hazards of earthquakes and strong winds.The loss of cross-section area of reinforcements and the reduction in strength of reinforcing steel and concrete cover induced by the chloride attack are considered.Moreover,the Poisson model is employed to obtain the occurrence probabilities of the individual and concurrent earthquake and strong wind events.The convolution integral is used to determine the joint probability distribution of combined load effects under simultaneous earthquakes and strong winds.Numerical results indicate that the structural failure probability under multiple hazards increases significantly during the bridge′s life-cycle due to the chloride corrosion effect.The contribution of each hazard event on the total structural failure probability varies with time.Thus,neglecting the combined influences of multiple hazards and chloride-induced corrosion may bring erroneous predictions in failure probability estimates of RC bridges.
基金supported by the National Natural Science Foundation of China(Nos.52034009 and 51974319)the Yue Qi Distinguished Scholar Project(No.2020JCB01)。
文摘The quantitative determination and evaluation of rock brittleness are crucial for the estimation of excavation efficiency and the improvement of hydraulic fracturing efficiency.Therefore,a“three-stage”triaxial loading and unloading stress path is designed and proposed.Subsequently,six brittleness indices are selected.In addition,the evolution characteristics of the six brittleness indices selected are characterized based on the bedding effect and the effect of confining pressure.Then,the entropy weight method(EWM)is introduced to assign weight to the six brittleness indices,and the comprehensive brittleness index Bcis defined and evaluated.Next,the new brittleness classification standard is determined,and the brittleness differences between the two stress paths are quantified.Finally,compared with the previous evaluation methods,the rationality of the proposed comprehensive brittleness index Bcis also verified.These results indicate that the proposed brittleness index Bccan reflect the brittle characteristics of deep bedded sandstone from the perspective of the whole life-cycle evolution process.Accordingly,the method proposed seems to offer reliable evaluations of the brittleness of deep bedded sandstone in deep engineering practices,although further validation is necessary.
文摘The development and deployment of Carbon dioxide Capture and Storage (CCS) technology is a cornerstone of the Norwegian government's climate strategy. A number of projects are currently evaluated/planned along the Norwegian West Coast, one at Tjeldbergodden. COe from this project will be utilized in part for enhanced oil recovery in the Halten oil field, in the Norwegian Sea. We study a potential design of such a system. A combined cycle power plant with a gross power output of 832 MW is combined with CO2 capture plant based on a post-combustion capture using amines as a solvent. The captured CO2 is used for enhanced oil recovery (EOR). We employ a hybrid life-cycle assessment (LCA) method to assess the environmental impacts of the system. The study focuses on the modifications and operations of the platform during EOR. We allocate the impacts connected to the capture of CO2 to electricity production, and the impacts connected to the transport and storage of CO2 to the oil produced. Our study shows a substantial reduction of the greenhouse gas emissions from power production by 80% to 75 g·(kW·h)^-1. It also indicates a reduction of the emissions associated with oil production per unit oil produced, mostly due to the increased oil production. Reductions are especially significant if the additional power demand due to EOR leads to power supply from the land.
基金supported by the National Natural Science Foundation of China(71732001,51878311,72271106,U21A20151,and 71821001)Engineering Fronts Project(2021-HYZD-5-13)+1 种基金Major Science&Technology Project of Hubei(2020ACA006)China Scholarship Council(202006160115).
文摘During the coronavirus disease 2019 (COVID-19) emergency, many hospitals were built or renovated around the world to meet the challenges posed by the rising number of infected cases. Environmental management in the hospital life cycle is vital in preventing nosocomial infection and includes many infection control procedures. In certain urgent situations, a hospital must be completed quickly, and work process approval and supervision must therefore be accelerated. Thus, many works cannot be checked in detail. This results in a lack of work liability control and increases the difficulty of ensuring the fulfillment of key infection prevention measures. This study investigates how blockchain technology can transform the work quality inspection workflow to assist in nosocomial infection control under a fast delivery requirement. A blockchain-based life-cycle environmental management framework is proposed to track the fulfillment of crucial infection control measures in the design, construction, and operation stages of hospitals. The proposed framework allows for work quality checking after the work is completed, when some work cannot be checked on time. Illustrative use cases are selected to demonstrate the capabilities of the developed solution. This study provides new insights into applying blockchain technology to address the challenge of environmental management brought by rapid delivery requirements.
基金Under the auspices of the National Natural Science Foundation of China(No.41101567)
文摘As the construction sector is a major energy consumer and thus a significant contributor of CO_2 emissions in China,it is important to consider carbon reduction in this industry.This study analyzed six life-cycle stages and calculated the life-cycle CO_2 emissions of the construction sector in 30 Chinese provincial jurisdictions to understand the disparity among them.Results show that building materials production was the key stage for carbon reduction in the construction sector,followed by the building operation stage.External variables,e.g.,economic growth,industrial structure,urbanization,price fluctuation,and marketization,were significantly correlated with the emission intensity of the construction sector.Specifically,economic growth exhibited an inverted U-shaped relation with CO_2 emissions per capita and per area during the period examined.Secondary industry and land urbanization were negatively correlated with CO_2 emission intensity indicators from the construction sector,whereas tertiary industry and urbanization were positively correlated.Price indices and marketization had negative effects on CO_2 emission intensity.The policy implications of our findings are that cleaner technologies should be encouraged for cement providers,and green purchasing rules for the construction sector should also be established.Pricing tools(e.g.,resource taxes)could help to adjust the demand for raw materials and energy.