Currently,more than ten ultrahigh arch dams have been constructed or are being constructed in China.Safety control is essential to long-term operation of these dams.This study employed the flexibility coefficient and ...Currently,more than ten ultrahigh arch dams have been constructed or are being constructed in China.Safety control is essential to long-term operation of these dams.This study employed the flexibility coefficient and plastic complementary energy norm to assess the structural safety of arch dams.A comprehensive analysis was conducted,focusing on differences among conventional methods in characterizing the structural behavior of the Xiaowan arch dam in China.Subsequently,the spatiotemporal characteristics of the measured performance of the Xiaowan dam were explored,including periodicity,convergence,and time-effect characteristics.These findings revealed the governing mechanism of main factors.Furthermore,a heterogeneous spatial panel vector model was developed,considering both common factors and specific factors affecting the safety and performance of arch dams.This model aims to comprehensively illustrate spatial heterogeneity between the entire structure and local regions,introducing a specific effect quantity to characterize local deformation differences.Ultimately,the proposed model was applied to the Xiaowan arch dam,accurately quantifying the spatiotemporal heterogeneity of dam performance.Additionally,the spatiotemporal distri-bution characteristics of environmental load effects on different parts of the dam were reasonably interpreted.Validation of the model prediction enhances its credibility,leading to the formulation of health diagnosis criteria for future long-term operation of the Xiaowan dam.The findings not only enhance the predictive ability and timely control of ultrahigh arch dams'performance but also provide a crucial basis for assessing the effectiveness of engineering treatment measures.展开更多
The advantages of a flat-panel X-ray source(FPXS)make it a promising candidate for imaging applications.Accurate imaging-system modeling and projection simulation are critical for analyzing imaging performance and res...The advantages of a flat-panel X-ray source(FPXS)make it a promising candidate for imaging applications.Accurate imaging-system modeling and projection simulation are critical for analyzing imaging performance and resolving overlapping projection issues in FPXS.The conventional analytical ray-tracing approach is limited by the number of patterns and is not applicable to FPXS-projection calculations.However,the computation time of Monte Carlo(MC)simulation is independent of the size of the patterned arrays in FPXS.This study proposes two high-efficiency MC projection simulators for FPXS:a graphics processing unit(GPU)-based phase-space sampling MC(gPSMC)simulator and GPU-based fluence sampling MC(gFSMC)simulator.The two simulators comprise three components:imaging-system modeling,photon initialization,and physical-interaction simulations in the phantom.Imaging-system modeling was performed by modeling the FPXS,imaging geometry,and detector.The gPSMC simulator samples the initial photons from the phase space,whereas the gFSMC simulator performs photon initialization from the calculated energy spectrum and fluence map.The entire process of photon interaction with the geometry and arrival at the detector was simulated in parallel using multiple GPU kernels,and projections based on the two simulators were calculated.The accuracies of the two simulators were evaluated by comparing them with the conventional analytical ray-tracing approach and acquired projections,and the efficiencies were evaluated by comparing the computation time.The results of simulated and realistic experiments illustrate the accuracy and efficiency of the proposed gPSMC and gFSMC simulators in the projection calculation of various phantoms.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
The internal flow field study of car compartments is an important step in railroad vehicle design and optimization. The flow field profile has a significant impact on the temperature distribution and passenger comfort...The internal flow field study of car compartments is an important step in railroad vehicle design and optimization. The flow field profile has a significant impact on the temperature distribution and passenger comfort level. Experimental studies on flow field can yield accurate results but carry a high time and computational cost. In contrast, the numerical simulation method can yield an internal flow field profile in less time than an experimental study. This study aims to improve the computational efficiency of numerical simulation by adapting two simplified models—the porous media model and the porous jump face model—to study the internal flow field of a railroad car compartment. The results provided by both simplified models are compared with the original numerical simulation model and with experimental data. Based on the results, the porous media model has a better agreement with the original model and with the experimental results. The flow field parameters (temperature and velocity) of the porous media model have relatively small numerical errors, with a maximum numerical error of 4.7%. The difference between the numerical results of the original model and those of the porous media model is less than 1%. By replacing the original numerical simulation model with the porous media model, the flow field of subway car compartments can be calculated with a reduction of about 25% in computing resources, while maintaining good accuracy.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
In this review, we highlight some recent methodological and theoretical develop- ments in estimation and testing of large panel data models with cross-sectional dependence. The paper begins with a discussion of issues...In this review, we highlight some recent methodological and theoretical develop- ments in estimation and testing of large panel data models with cross-sectional dependence. The paper begins with a discussion of issues of cross-sectional dependence, and introduces the concepts of weak and strong cross-sectional dependence. Then, the main attention is primarily paid to spatial and factor approaches for modeling cross-sectional dependence for both linear and nonlinear (nonparametric and semiparametric) panel data models. Finally, we conclude with some speculations on future research directions.展开更多
The present paper reviews the vibro-acoustic modelling of extruded aluminium train floor structures including the state-of-the-art of its industrial applications, as well as the most recent developments on mid-frequen...The present paper reviews the vibro-acoustic modelling of extruded aluminium train floor structures including the state-of-the-art of its industrial applications, as well as the most recent developments on mid-frequency mod- elling techniques in general. With the common purpose to predict mid-frequency vibro-acoustic responses of stiffened panel structures to an acceptable accuracy at a reasonable computational cost, relevant techniques are mainly based on one of the following three types of mid-frequency vibro- acoustic modelling principles: (1) enhanced deterministic methods, (2) enhanced statistical methods, and (3) hybrid deterministic/statistical methods. It is shown that, although recent developments have led to a significant step forward in industrial applicability, mature and adequate prediction tech- niques, however, are still very much required for solving sound transmission through, and radiation from, extruded aluminium panels used on high-speed trains. Due to their great potentials for predicting mid-frequency vibro-acoustics of stiffened panel structures, two of recently developed mid-frequency modelling approaches, i.e. the so-called hybrid finite element-statistical energy analysis (FE-SEA) and hybrid wave-based method- statistical energy analysis (WBM-SEA), are then recapitulated.展开更多
An original plastic equivalent model was proposed to solve the problem of excessive FEM simulation time when designing the press bend forming path and optimizing the process parameters of press bend forming of the int...An original plastic equivalent model was proposed to solve the problem of excessive FEM simulation time when designing the press bend forming path and optimizing the process parameters of press bend forming of the integrally stiffened aircraft panels. Based on the in-depth analysis of the mechanics of the bending and springback of the detailed model and the equivalent model of the integral panels,the plastic equivalent model of the virtual material with special initial yield stress and hardening coefficients was constructed. FEM results indicate that the objective of getting the similar contour with the same press bend forming path is achieved with the error less than 6%,and the efficiency of FEM simulation is improved by more than 80%. The plastic equivalent model is valuable and essential for the further research on the press bend forming process of large scale complicated integral panels.展开更多
We used simulated data to investigate both the small and large sample properties of the within-groups (WG) estimator and the first difference generalized method of moments (FD-GMM) estimator of a dynamic panel data (D...We used simulated data to investigate both the small and large sample properties of the within-groups (WG) estimator and the first difference generalized method of moments (FD-GMM) estimator of a dynamic panel data (DPD) model. The magnitude of WG and FD-GMM estimates are almost the same for square panels. WG estimator performs best for long panels such as those with time dimension as large as 50. The advantage of FD-GMM estimator however, is observed on panels that are long and wide, say with time dimension at least 25 and cross-section dimension size of at least 30. For small-sized panels, the two methods failed since their optimality was established in the context of asymptotic theory. We developed parametric bootstrap versions of WG and FD-GMM estimators. Simulation study indicates the advantages of the bootstrap methods under small sample cases on the assumption that variances of the individual effects and the disturbances are of similar magnitude. The boostrapped WG and FD-GMM estimators are optimal for small samples.展开更多
Glass fi ber reinforced gypsum(GFRG) wall panels are prefabricated panels with hollow cores, originally developed in Australia and subsequently adopted by India and China for use in buildings. This paper discusses ide...Glass fi ber reinforced gypsum(GFRG) wall panels are prefabricated panels with hollow cores, originally developed in Australia and subsequently adopted by India and China for use in buildings. This paper discusses identifi cation and calibration of a suitable hysteretic model for GFRG wall panels fi lled with reinforced concrete. As considerable pinching was observed in the experimental results, a suitable hysteretic model with pinched hysteretic rule is used to conduct a series of quasi-static as inelastic hysteretic response analyses of GFRG panels with two different widths. The calibration of the pinching model parameters was carried out to approximately match the simulated and experimental responses up to 80% of the peak load in the post peak region. Interestingly, the same values of various parameters(energy dissipation and pinching related parameters) were obtained for all fi ve test specimens.展开更多
This work presents a numerical simulation of ballistic penetration and high velocity impact behavior of plain and reinforced concrete panels.This paper is divided into two parts.The first part consists of numerical mo...This work presents a numerical simulation of ballistic penetration and high velocity impact behavior of plain and reinforced concrete panels.This paper is divided into two parts.The first part consists of numerical modeling of reinforced concrete panel penetrated with a spherical projectile using concrete damage plasticity(CDP)model,while the second part focuses on the comparison of CDP model and Johnson-Holmquist-2(JH-2)damage model and their ability to describe the behavior of concrete panel under impact loads.The first and second concrete panels have dimensions of 1500 mm1500 mm150 mm and 675 mm675 mm200 mm,respectively,and are meshed using 8-node hexahedron solid elements.The impact object used in the first part is a spherical projectile of 150 mm diameter,while in the second part steel projectile of a length of 152 mm is modeled as rigid element.Failure and scabbing characteristics are studied in the first part.In the second part,the comparison results are presented as damage contours,kinetic energy of projectile and internal energy of the concrete.The results revealed a severe fracture of the panel and high kinetic energy of the projectile using CDP model comparing to the JH-2 model.In addition,the internal energy of concrete using CDP model was found to be less comparing to the JH-2 model.展开更多
The configuration of an airway(or production drift)in panel cave mines is different from the typical(straight)mine airway designs.The drawpoints are connected to the airway(cross-cuts),which allows airflow from the ca...The configuration of an airway(or production drift)in panel cave mines is different from the typical(straight)mine airway designs.The drawpoints are connected to the airway(cross-cuts),which allows airflow from the cave into the airway or air loss from the airway into the cave due to the ventilation approach and cave porosity.These affect airflow in the production drifts,but it is difficult to investigate these conditions from field or laboratory scaled studies.Therefore,this study develops discrete and continuum computational fluid dynamics(CFD)models to study the effects of the ventilation approach and cave porosity on the airway resistance.Our findings show that:with active undercut ventilation,a unique resistance model is required for the airway in panel cave mines;and an increase in cave porosity decreases the drift’s resistance.These findings provide essential tools for a panel cave ventilation design.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.52079046).
文摘Currently,more than ten ultrahigh arch dams have been constructed or are being constructed in China.Safety control is essential to long-term operation of these dams.This study employed the flexibility coefficient and plastic complementary energy norm to assess the structural safety of arch dams.A comprehensive analysis was conducted,focusing on differences among conventional methods in characterizing the structural behavior of the Xiaowan arch dam in China.Subsequently,the spatiotemporal characteristics of the measured performance of the Xiaowan dam were explored,including periodicity,convergence,and time-effect characteristics.These findings revealed the governing mechanism of main factors.Furthermore,a heterogeneous spatial panel vector model was developed,considering both common factors and specific factors affecting the safety and performance of arch dams.This model aims to comprehensively illustrate spatial heterogeneity between the entire structure and local regions,introducing a specific effect quantity to characterize local deformation differences.Ultimately,the proposed model was applied to the Xiaowan arch dam,accurately quantifying the spatiotemporal heterogeneity of dam performance.Additionally,the spatiotemporal distri-bution characteristics of environmental load effects on different parts of the dam were reasonably interpreted.Validation of the model prediction enhances its credibility,leading to the formulation of health diagnosis criteria for future long-term operation of the Xiaowan dam.The findings not only enhance the predictive ability and timely control of ultrahigh arch dams'performance but also provide a crucial basis for assessing the effectiveness of engineering treatment measures.
文摘The advantages of a flat-panel X-ray source(FPXS)make it a promising candidate for imaging applications.Accurate imaging-system modeling and projection simulation are critical for analyzing imaging performance and resolving overlapping projection issues in FPXS.The conventional analytical ray-tracing approach is limited by the number of patterns and is not applicable to FPXS-projection calculations.However,the computation time of Monte Carlo(MC)simulation is independent of the size of the patterned arrays in FPXS.This study proposes two high-efficiency MC projection simulators for FPXS:a graphics processing unit(GPU)-based phase-space sampling MC(gPSMC)simulator and GPU-based fluence sampling MC(gFSMC)simulator.The two simulators comprise three components:imaging-system modeling,photon initialization,and physical-interaction simulations in the phantom.Imaging-system modeling was performed by modeling the FPXS,imaging geometry,and detector.The gPSMC simulator samples the initial photons from the phase space,whereas the gFSMC simulator performs photon initialization from the calculated energy spectrum and fluence map.The entire process of photon interaction with the geometry and arrival at the detector was simulated in parallel using multiple GPU kernels,and projections based on the two simulators were calculated.The accuracies of the two simulators were evaluated by comparing them with the conventional analytical ray-tracing approach and acquired projections,and the efficiencies were evaluated by comparing the computation time.The results of simulated and realistic experiments illustrate the accuracy and efficiency of the proposed gPSMC and gFSMC simulators in the projection calculation of various phantoms.
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The internal flow field study of car compartments is an important step in railroad vehicle design and optimization. The flow field profile has a significant impact on the temperature distribution and passenger comfort level. Experimental studies on flow field can yield accurate results but carry a high time and computational cost. In contrast, the numerical simulation method can yield an internal flow field profile in less time than an experimental study. This study aims to improve the computational efficiency of numerical simulation by adapting two simplified models—the porous media model and the porous jump face model—to study the internal flow field of a railroad car compartment. The results provided by both simplified models are compared with the original numerical simulation model and with experimental data. Based on the results, the porous media model has a better agreement with the original model and with the experimental results. The flow field parameters (temperature and velocity) of the porous media model have relatively small numerical errors, with a maximum numerical error of 4.7%. The difference between the numerical results of the original model and those of the porous media model is less than 1%. By replacing the original numerical simulation model with the porous media model, the flow field of subway car compartments can be calculated with a reduction of about 25% in computing resources, while maintaining good accuracy.
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 the National Natural Science Foundation of China(71131008(Key Project)and 71271179)
文摘In this review, we highlight some recent methodological and theoretical develop- ments in estimation and testing of large panel data models with cross-sectional dependence. The paper begins with a discussion of issues of cross-sectional dependence, and introduces the concepts of weak and strong cross-sectional dependence. Then, the main attention is primarily paid to spatial and factor approaches for modeling cross-sectional dependence for both linear and nonlinear (nonparametric and semiparametric) panel data models. Finally, we conclude with some speculations on future research directions.
基金sponsored by the NationalNatural foundation of China(Grant Nos.U1434201 and 51175300)
文摘The present paper reviews the vibro-acoustic modelling of extruded aluminium train floor structures including the state-of-the-art of its industrial applications, as well as the most recent developments on mid-frequency mod- elling techniques in general. With the common purpose to predict mid-frequency vibro-acoustic responses of stiffened panel structures to an acceptable accuracy at a reasonable computational cost, relevant techniques are mainly based on one of the following three types of mid-frequency vibro- acoustic modelling principles: (1) enhanced deterministic methods, (2) enhanced statistical methods, and (3) hybrid deterministic/statistical methods. It is shown that, although recent developments have led to a significant step forward in industrial applicability, mature and adequate prediction tech- niques, however, are still very much required for solving sound transmission through, and radiation from, extruded aluminium panels used on high-speed trains. Due to their great potentials for predicting mid-frequency vibro-acoustics of stiffened panel structures, two of recently developed mid-frequency modelling approaches, i.e. the so-called hybrid finite element-statistical energy analysis (FE-SEA) and hybrid wave-based method- statistical energy analysis (WBM-SEA), are then recapitulated.
基金Project(50675010) supported by the National Natural Science Foundation of China
文摘An original plastic equivalent model was proposed to solve the problem of excessive FEM simulation time when designing the press bend forming path and optimizing the process parameters of press bend forming of the integrally stiffened aircraft panels. Based on the in-depth analysis of the mechanics of the bending and springback of the detailed model and the equivalent model of the integral panels,the plastic equivalent model of the virtual material with special initial yield stress and hardening coefficients was constructed. FEM results indicate that the objective of getting the similar contour with the same press bend forming path is achieved with the error less than 6%,and the efficiency of FEM simulation is improved by more than 80%. The plastic equivalent model is valuable and essential for the further research on the press bend forming process of large scale complicated integral panels.
文摘We used simulated data to investigate both the small and large sample properties of the within-groups (WG) estimator and the first difference generalized method of moments (FD-GMM) estimator of a dynamic panel data (DPD) model. The magnitude of WG and FD-GMM estimates are almost the same for square panels. WG estimator performs best for long panels such as those with time dimension as large as 50. The advantage of FD-GMM estimator however, is observed on panels that are long and wide, say with time dimension at least 25 and cross-section dimension size of at least 30. For small-sized panels, the two methods failed since their optimality was established in the context of asymptotic theory. We developed parametric bootstrap versions of WG and FD-GMM estimators. Simulation study indicates the advantages of the bootstrap methods under small sample cases on the assumption that variances of the individual effects and the disturbances are of similar magnitude. The boostrapped WG and FD-GMM estimators are optimal for small samples.
文摘Glass fi ber reinforced gypsum(GFRG) wall panels are prefabricated panels with hollow cores, originally developed in Australia and subsequently adopted by India and China for use in buildings. This paper discusses identifi cation and calibration of a suitable hysteretic model for GFRG wall panels fi lled with reinforced concrete. As considerable pinching was observed in the experimental results, a suitable hysteretic model with pinched hysteretic rule is used to conduct a series of quasi-static as inelastic hysteretic response analyses of GFRG panels with two different widths. The calibration of the pinching model parameters was carried out to approximately match the simulated and experimental responses up to 80% of the peak load in the post peak region. Interestingly, the same values of various parameters(energy dissipation and pinching related parameters) were obtained for all fi ve test specimens.
文摘This work presents a numerical simulation of ballistic penetration and high velocity impact behavior of plain and reinforced concrete panels.This paper is divided into two parts.The first part consists of numerical modeling of reinforced concrete panel penetrated with a spherical projectile using concrete damage plasticity(CDP)model,while the second part focuses on the comparison of CDP model and Johnson-Holmquist-2(JH-2)damage model and their ability to describe the behavior of concrete panel under impact loads.The first and second concrete panels have dimensions of 1500 mm1500 mm150 mm and 675 mm675 mm200 mm,respectively,and are meshed using 8-node hexahedron solid elements.The impact object used in the first part is a spherical projectile of 150 mm diameter,while in the second part steel projectile of a length of 152 mm is modeled as rigid element.Failure and scabbing characteristics are studied in the first part.In the second part,the comparison results are presented as damage contours,kinetic energy of projectile and internal energy of the concrete.The results revealed a severe fracture of the panel and high kinetic energy of the projectile using CDP model comparing to the JH-2 model.In addition,the internal energy of concrete using CDP model was found to be less comparing to the JH-2 model.
基金support from the National Institute for Occupational Safety and Health(NIOSH)(No.200-2014-59613)for conducting this research.
文摘The configuration of an airway(or production drift)in panel cave mines is different from the typical(straight)mine airway designs.The drawpoints are connected to the airway(cross-cuts),which allows airflow from the cave into the airway or air loss from the airway into the cave due to the ventilation approach and cave porosity.These affect airflow in the production drifts,but it is difficult to investigate these conditions from field or laboratory scaled studies.Therefore,this study develops discrete and continuum computational fluid dynamics(CFD)models to study the effects of the ventilation approach and cave porosity on the airway resistance.Our findings show that:with active undercut ventilation,a unique resistance model is required for the airway in panel cave mines;and an increase in cave porosity decreases the drift’s resistance.These findings provide essential tools for a panel cave ventilation design.