This paper takes the assessment and evaluation of computational mechanics course as the background,and constructs a diversified course evaluation system that is student-centered and integrates both quantitative and qu...This paper takes the assessment and evaluation of computational mechanics course as the background,and constructs a diversified course evaluation system that is student-centered and integrates both quantitative and qualitative evaluation methods.The system not only pays attention to students’practical operation and theoretical knowledge mastery but also puts special emphasis on the cultivation of students’innovative abilities.In order to realize a comprehensive and objective evaluation,the assessment and evaluation method of the entropy weight model combining TOPSIS(Technique for Order Preference by Similarity to Ideal Solution)multi-attribute decision analysis and entropy weight theory is adopted,and its validity and practicability are verified through example analysis.This method can not only comprehensively and objectively evaluate students’learning outcomes,but also provide a scientific decision-making basis for curriculum teaching reform.The implementation of this diversified course evaluation system can better reflect the comprehensive ability of students and promote the continuous improvement of teaching quality.展开更多
This paper presents a micromechanics-based Cosserat continuum model for microstructured granular materials.By utilizing this model,the macroscopic constitutive parameters of granular materials with different microstru...This paper presents a micromechanics-based Cosserat continuum model for microstructured granular materials.By utilizing this model,the macroscopic constitutive parameters of granular materials with different microstructures are expressed as sums of microstructural information.The microstructures under consideration can be classified into three categories:a medium-dense microstructure,a dense microstructure consisting of one-sized particles,and a dense microstructure consisting of two-sized particles.Subsequently,the Cosserat elastoplastic model,along with its finite element formulation,is derived using the extended Drucker-Prager yield criteria.To investigate failure behaviors,numerical simulations of granular materials with different microstructures are conducted using the ABAQUS User Element(UEL)interface.It demonstrates the capacity of the proposed model to simulate the phenomena of strain-softening and strain localization.The study investigates the influence of microscopic parameters,including contact stiffness parameters and characteristic length,on the failure behaviors of granularmaterials withmicrostructures.Additionally,the study examines themesh independence of the presented model and establishes its relationship with the characteristic length.A comparison is made between finite element simulations and discrete element simulations for a medium-dense microstructure,revealing a good agreement in results during the elastic stage.Somemacroscopic parameters describing plasticity are shown to be partially related to microscopic factors such as confining pressure and size of the representative volume element.展开更多
In this study,a numerical analysis was conducted on the ductile fracture of a 2-mm diameter Mg-1Zn-0.5Mn-0.5Sr-0.1Ca alloy wire during drawing.The hexagonally close-packed crystal structure of Mg alloys causes asymmet...In this study,a numerical analysis was conducted on the ductile fracture of a 2-mm diameter Mg-1Zn-0.5Mn-0.5Sr-0.1Ca alloy wire during drawing.The hexagonally close-packed crystal structure of Mg alloys causes asymmetric fracture behavior,especially in the compression region.The aim of this study is to develop a comprehensive damage model for Mg alloy wire that accurately predicts ductile fracture,with a focus on the compression region.A novel experimental method was introduced to measure the ductile fracture of Mg alloy wires under different stress states.The wire drawing process was simulated using the Generalized Incremental Stress-State dependent damage(GISSMO)Model and the Semi-Analytical Model for Polymers(SAMP)model.The damage model's prediction and the experimental results were found to be in excellent agreement,especially in determining crack initiation.Computational analysis established a safe zone diagram for die angle and reduction ratio,and experimental validation confirmed the feasibility of this approach.The proposed damage model can provide a practical and reliable analysis for optimizing the drawing process of Mg alloy wire.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
Damage statistical mechanics model of horizontal section height in the top caving was constructed in the paper. The influence factors including supporting pressure, dip angle and characteristic of coal on horizontal s...Damage statistical mechanics model of horizontal section height in the top caving was constructed in the paper. The influence factors including supporting pressure, dip angle and characteristic of coal on horizontal section height were analyzed as well. By terms of the practice project analysis, the horizontal section height increases with the increase of dip angle β and thickness of coal seam M. Dip angle of coal seam β has tremendous impact on horizontal section height, while thickness of coal seam M has slight impact. When thickness of coal seam is below 10m, horizontal section height increases sharply. While thickness exceeds 15m, it is not major factor influencing on horizontal section height any long.展开更多
A non-linear continuum damage model was presented based on the irreversible thermodynamics framework developed by LEMAITRE and CHABOCHE. The proposed model was formulated by taking into account the influence of loadin...A non-linear continuum damage model was presented based on the irreversible thermodynamics framework developed by LEMAITRE and CHABOCHE. The proposed model was formulated by taking into account the influence of loading frequency on fatigue life. The parameters H and c are constants for frequency-independent materials, but functions of cyclic frequency for frequency-dependent materials. In addition, the expression of the model was discussed in detail at different stress ratios (R). Fatigue test data of AlZnMgCu1.5 aluminium alloy and AMg6N alloy were used to verify the proposed model. The results showed that the model possesses a good ability of predicting fatigue life at different loading frequencies and stress ratios.展开更多
A new mechanics model, which reveals additional longitudinal force transmission between the continuously welded rails and the bridges, is established on the fact that the influence of the mutual relative displacement ...A new mechanics model, which reveals additional longitudinal force transmission between the continuously welded rails and the bridges, is established on the fact that the influence of the mutual relative displacement (among) the rail, the sleeper and the beam is taken into account. An example is presented and numerical results are compared. The results show that the additional longitudinal forces calculated with the new model are less than those of the previous, especially in the case of the flexible pier bridges. The new model is also suitable for the analysis of the additional longitudinal force transmission between rails and bridges of ballastless track with small resistance fasteners without taking the sleeper displacement into account, and compared with the ballast bridges, the ballastless bridges have a much stronger additional longitudinal force transmission between the continuously welded rails and the bridges.展开更多
Based on break characteristics of roofs in fully mechanized top-coal mining of thick shallow coal seams, a fracture mechanics model was built, and the criterion of crack propagation in the main roof was derived using ...Based on break characteristics of roofs in fully mechanized top-coal mining of thick shallow coal seams, a fracture mechanics model was built, and the criterion of crack propagation in the main roof was derived using the fracture mechanics theory. The relationships between the fracture length of the roof and the working resistance of the supports were discovered, and the correlations between the load on the overlying strata and the ratio of the crack's length to the thickness of the roof were obtained. Using a working face of Jindi Coal Mine, Xing county Shanxi province as an example, the relationships between the fracture length of the roof and the working resistance of the supports were analysed in detail. The results give a design basis in hydraulic top coal caving supports, which could provide useful references in the practical application. On-site experiment proves that the periodic weighting step interval of the caving face is 15–16 m, which is basically consistent with the theoretical analysis results, and indicates that the mechanized caving hydraulic support is capable of meeting the support requirements in the mining of a super-thick but shallowly buried coal seam.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 geometric model of curved blood vessels is established based on some reasonable hypotheses; the nonlinear motion mechanics model of the curved blood vessel is established according to basic mechanics laws. This mode...A geometric model of curved blood vessels is established based on some reasonable hypotheses; the nonlinear motion mechanics model of the curved blood vessel is established according to basic mechanics laws. This model includes much more physiological factors. It couples the interaction of blood flow with mechanical factors such as the displacement, deformation, strain and stress etc. of the curved blood vessel. It is of great importance for investigating the circulation rules of the cardiovascular system and the nonlinear pulse wave propagation in curved blood vessels.展开更多
The factors influencing on soil expansion are reviewed in the paper. A mechanics model to determine swelling potential of expansive soils is presented. The mechanics model is based on the softening of expansive soil f...The factors influencing on soil expansion are reviewed in the paper. A mechanics model to determine swelling potential of expansive soils is presented. The mechanics model is based on the softening of expansive soil following absorption of water. The constitutive relationships of the mechanics model include the relationship among swelling under free load, swelling under load, and vertical pressure, and the relationship of swelling under free loading and swelling pressure. A concept of additional compression modulus is introduced and the method determining the modulus is proposed. Finally, the predicted results of swelling potential using the mechanics model compare well with the measured data.展开更多
Successful modeling and/or design of engineering systems often requires one to address the impact of multiple "design variables" on the prescribed outcome.There are often multiple,competing objectives based on which...Successful modeling and/or design of engineering systems often requires one to address the impact of multiple "design variables" on the prescribed outcome.There are often multiple,competing objectives based on which we assess the outcome of optimization.Since accurate,high fidelity models are typically time consuming and computationally expensive,comprehensive evaluations can be conducted only if an efficient framework is available.Furthermore,informed decisions of the model/hardware's overall performance rely on an adequate understanding of the global,not local,sensitivity of the individual design variables on the objectives.The surrogate-based approach,which involves approximating the objectives as continuous functions of design variables from limited data,offers a rational framework to reduce the number of important input variables,i.e.,the dimension of a design or modeling space.In this paper,we review the fundamental issues that arise in surrogate-based analysis and optimization,highlighting concepts,methods,techniques,as well as modeling implications for mechanics problems.To aid the discussions of the issues involved,we summarize recent efforts in investigating cryogenic cavitating flows,active flow control based on dielectric barrier discharge concepts,and lithium(Li)-ion batteries.It is also stressed that many multi-scale mechanics problems can naturally benefit from the surrogate approach for "scale bridging."展开更多
Because the result of the MB fractal model contradicts with the classical contact mechanics, a revised elastoplastic contact model of a single asperity is developed based on fractal theory. The critical areas of a sin...Because the result of the MB fractal model contradicts with the classical contact mechanics, a revised elastoplastic contact model of a single asperity is developed based on fractal theory. The critical areas of a single asperity are scale dependent, with an increase in the contact load and contact area, a transition from elastic, elastoplastic to full plastic deformation takes place in this order. In considering the size distribution function, analytic expression between the total contact load and the real contact area on the contact surface is obtained. The elastic, elastoplastic and full plastic contact load are obtained by the critical elastic contact area of the biggest asperity and maximun contact area of a single asperity. The results show that a rough surface is firstly in elastic deformation. As the load increases, elastoplastic or full plastic deformation takes place. For constant characteristic length scale G, the slope of load-area relation is proportional to fractal dimension D. For constant fractal dimension D, the slope of load-area relation is inversely proportional to G. For constant D and G, the slope of load-area relation is inversely proportional to property of the material ~b, namely with the same load, the material of rough surface is softer, and the total contact area is larger. The contact mechanics model provides a foundation for study of the friction, wear and seal performance of rough surfaces.展开更多
In this paper, a cluster model in particle flow code was used to simulate granite specimens after heat treatment under uniaxial compression. The results demonstrated that micro-cracks are randomly distributed in the s...In this paper, a cluster model in particle flow code was used to simulate granite specimens after heat treatment under uniaxial compression. The results demonstrated that micro-cracks are randomly distributed in the specimen when the temperature is below 300?C, and have partial coalescence when the temperature is up to 450?C, then form macro-cracks when the temperature is above 600?C. There is more inter-granular cracking than intra-granular cracking, and their ratio increases with increasing temperature.The micro-cracks are almost constant when the temperature decreases from 900?C to room temperature, except for quartz α–β phase transition temperature(573?C). The fracture evolution process is obviously affected by these cracks, especially at 600–900?C. Elevated temperature leads to easily developed displacement between the grains, and the capacity to store strain energy becomes weaker, corresponding to the plasticity of granite after heat treatment.展开更多
基金2024 Key Project of Teaching Reform Research and Practice in Higher Education in Henan Province“Exploration and Practice of Training Model for Outstanding Students in Basic Mechanics Discipline”(2024SJGLX094)Henan Province“Mechanics+X”Basic Discipline Outstanding Student Training Base2024 Research and Practice Project of Higher Education Teaching Reform in Henan University of Science and Technology“Optimization and Practice of Ability-Oriented Teaching Mode for Computational Mechanics Course:A New Exploration in Cultivating Practical Simulation Engineers”(2024BK074)。
文摘This paper takes the assessment and evaluation of computational mechanics course as the background,and constructs a diversified course evaluation system that is student-centered and integrates both quantitative and qualitative evaluation methods.The system not only pays attention to students’practical operation and theoretical knowledge mastery but also puts special emphasis on the cultivation of students’innovative abilities.In order to realize a comprehensive and objective evaluation,the assessment and evaluation method of the entropy weight model combining TOPSIS(Technique for Order Preference by Similarity to Ideal Solution)multi-attribute decision analysis and entropy weight theory is adopted,and its validity and practicability are verified through example analysis.This method can not only comprehensively and objectively evaluate students’learning outcomes,but also provide a scientific decision-making basis for curriculum teaching reform.The implementation of this diversified course evaluation system can better reflect the comprehensive ability of students and promote the continuous improvement of teaching quality.
基金the National Natural Science Foundation of China through Contract/Grant Numbers 12002245,12172263 and 11772237Chongqing Jiaotong University through Contract/Grant Number F1220038.
文摘This paper presents a micromechanics-based Cosserat continuum model for microstructured granular materials.By utilizing this model,the macroscopic constitutive parameters of granular materials with different microstructures are expressed as sums of microstructural information.The microstructures under consideration can be classified into three categories:a medium-dense microstructure,a dense microstructure consisting of one-sized particles,and a dense microstructure consisting of two-sized particles.Subsequently,the Cosserat elastoplastic model,along with its finite element formulation,is derived using the extended Drucker-Prager yield criteria.To investigate failure behaviors,numerical simulations of granular materials with different microstructures are conducted using the ABAQUS User Element(UEL)interface.It demonstrates the capacity of the proposed model to simulate the phenomena of strain-softening and strain localization.The study investigates the influence of microscopic parameters,including contact stiffness parameters and characteristic length,on the failure behaviors of granularmaterials withmicrostructures.Additionally,the study examines themesh independence of the presented model and establishes its relationship with the characteristic length.A comparison is made between finite element simulations and discrete element simulations for a medium-dense microstructure,revealing a good agreement in results during the elastic stage.Somemacroscopic parameters describing plasticity are shown to be partially related to microscopic factors such as confining pressure and size of the representative volume element.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.2020R1A2C2010986,2022M3H4A1A04085301)。
文摘In this study,a numerical analysis was conducted on the ductile fracture of a 2-mm diameter Mg-1Zn-0.5Mn-0.5Sr-0.1Ca alloy wire during drawing.The hexagonally close-packed crystal structure of Mg alloys causes asymmetric fracture behavior,especially in the compression region.The aim of this study is to develop a comprehensive damage model for Mg alloy wire that accurately predicts ductile fracture,with a focus on the compression region.A novel experimental method was introduced to measure the ductile fracture of Mg alloy wires under different stress states.The wire drawing process was simulated using the Generalized Incremental Stress-State dependent damage(GISSMO)Model and the Semi-Analytical Model for Polymers(SAMP)model.The damage model's prediction and the experimental results were found to be in excellent agreement,especially in determining crack initiation.Computational analysis established a safe zone diagram for die angle and reduction ratio,and experimental validation confirmed the feasibility of this approach.The proposed damage model can provide a practical and reliable analysis for optimizing the drawing process of Mg alloy wire.
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This work was financially supported by the National Natural Science fund of China (No.50274058).
文摘Damage statistical mechanics model of horizontal section height in the top caving was constructed in the paper. The influence factors including supporting pressure, dip angle and characteristic of coal on horizontal section height were analyzed as well. By terms of the practice project analysis, the horizontal section height increases with the increase of dip angle β and thickness of coal seam M. Dip angle of coal seam β has tremendous impact on horizontal section height, while thickness of coal seam M has slight impact. When thickness of coal seam is below 10m, horizontal section height increases sharply. While thickness exceeds 15m, it is not major factor influencing on horizontal section height any long.
文摘A non-linear continuum damage model was presented based on the irreversible thermodynamics framework developed by LEMAITRE and CHABOCHE. The proposed model was formulated by taking into account the influence of loading frequency on fatigue life. The parameters H and c are constants for frequency-independent materials, but functions of cyclic frequency for frequency-dependent materials. In addition, the expression of the model was discussed in detail at different stress ratios (R). Fatigue test data of AlZnMgCu1.5 aluminium alloy and AMg6N alloy were used to verify the proposed model. The results showed that the model possesses a good ability of predicting fatigue life at different loading frequencies and stress ratios.
文摘A new mechanics model, which reveals additional longitudinal force transmission between the continuously welded rails and the bridges, is established on the fact that the influence of the mutual relative displacement (among) the rail, the sleeper and the beam is taken into account. An example is presented and numerical results are compared. The results show that the additional longitudinal forces calculated with the new model are less than those of the previous, especially in the case of the flexible pier bridges. The new model is also suitable for the analysis of the additional longitudinal force transmission between rails and bridges of ballastless track with small resistance fasteners without taking the sleeper displacement into account, and compared with the ballast bridges, the ballastless bridges have a much stronger additional longitudinal force transmission between the continuously welded rails and the bridges.
文摘Based on break characteristics of roofs in fully mechanized top-coal mining of thick shallow coal seams, a fracture mechanics model was built, and the criterion of crack propagation in the main roof was derived using the fracture mechanics theory. The relationships between the fracture length of the roof and the working resistance of the supports were discovered, and the correlations between the load on the overlying strata and the ratio of the crack's length to the thickness of the roof were obtained. Using a working face of Jindi Coal Mine, Xing county Shanxi province as an example, the relationships between the fracture length of the roof and the working resistance of the supports were analysed in detail. The results give a design basis in hydraulic top coal caving supports, which could provide useful references in the practical application. On-site experiment proves that the periodic weighting step interval of the caving face is 15–16 m, which is basically consistent with the theoretical analysis results, and indicates that the mechanized caving hydraulic support is capable of meeting the support requirements in the mining of a super-thick but shallowly buried coal seam.
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Project supported by the National Natural Science Foundation of China(No.19872009)the Foundation of University Key Teachers by the Ministry of Education(No.GG-831-10005-1497)
文摘A geometric model of curved blood vessels is established based on some reasonable hypotheses; the nonlinear motion mechanics model of the curved blood vessel is established according to basic mechanics laws. This model includes much more physiological factors. It couples the interaction of blood flow with mechanical factors such as the displacement, deformation, strain and stress etc. of the curved blood vessel. It is of great importance for investigating the circulation rules of the cardiovascular system and the nonlinear pulse wave propagation in curved blood vessels.
文摘The factors influencing on soil expansion are reviewed in the paper. A mechanics model to determine swelling potential of expansive soils is presented. The mechanics model is based on the softening of expansive soil following absorption of water. The constitutive relationships of the mechanics model include the relationship among swelling under free load, swelling under load, and vertical pressure, and the relationship of swelling under free loading and swelling pressure. A concept of additional compression modulus is introduced and the method determining the modulus is proposed. Finally, the predicted results of swelling potential using the mechanics model compare well with the measured data.
文摘Successful modeling and/or design of engineering systems often requires one to address the impact of multiple "design variables" on the prescribed outcome.There are often multiple,competing objectives based on which we assess the outcome of optimization.Since accurate,high fidelity models are typically time consuming and computationally expensive,comprehensive evaluations can be conducted only if an efficient framework is available.Furthermore,informed decisions of the model/hardware's overall performance rely on an adequate understanding of the global,not local,sensitivity of the individual design variables on the objectives.The surrogate-based approach,which involves approximating the objectives as continuous functions of design variables from limited data,offers a rational framework to reduce the number of important input variables,i.e.,the dimension of a design or modeling space.In this paper,we review the fundamental issues that arise in surrogate-based analysis and optimization,highlighting concepts,methods,techniques,as well as modeling implications for mechanics problems.To aid the discussions of the issues involved,we summarize recent efforts in investigating cryogenic cavitating flows,active flow control based on dielectric barrier discharge concepts,and lithium(Li)-ion batteries.It is also stressed that many multi-scale mechanics problems can naturally benefit from the surrogate approach for "scale bridging."
基金Supported by National Natural Science Foundation of China(Grant Nos.51105304,51475364)Shaanxi Provincial Natural Science Basic Research Plan of China(Grant No.2015JM5212)
文摘Because the result of the MB fractal model contradicts with the classical contact mechanics, a revised elastoplastic contact model of a single asperity is developed based on fractal theory. The critical areas of a single asperity are scale dependent, with an increase in the contact load and contact area, a transition from elastic, elastoplastic to full plastic deformation takes place in this order. In considering the size distribution function, analytic expression between the total contact load and the real contact area on the contact surface is obtained. The elastic, elastoplastic and full plastic contact load are obtained by the critical elastic contact area of the biggest asperity and maximun contact area of a single asperity. The results show that a rough surface is firstly in elastic deformation. As the load increases, elastoplastic or full plastic deformation takes place. For constant characteristic length scale G, the slope of load-area relation is proportional to fractal dimension D. For constant fractal dimension D, the slope of load-area relation is inversely proportional to G. For constant D and G, the slope of load-area relation is inversely proportional to property of the material ~b, namely with the same load, the material of rough surface is softer, and the total contact area is larger. The contact mechanics model provides a foundation for study of the friction, wear and seal performance of rough surfaces.
基金supported by the National Natural Science Foundation of Jiangsu Province of China for Distinguished Young Scholars (Grant BK20150005)the Fundamental Research Funds for the Central Universities (China University of Mining and Technology) (Grant 2014XT03)
文摘In this paper, a cluster model in particle flow code was used to simulate granite specimens after heat treatment under uniaxial compression. The results demonstrated that micro-cracks are randomly distributed in the specimen when the temperature is below 300?C, and have partial coalescence when the temperature is up to 450?C, then form macro-cracks when the temperature is above 600?C. There is more inter-granular cracking than intra-granular cracking, and their ratio increases with increasing temperature.The micro-cracks are almost constant when the temperature decreases from 900?C to room temperature, except for quartz α–β phase transition temperature(573?C). The fracture evolution process is obviously affected by these cracks, especially at 600–900?C. Elevated temperature leads to easily developed displacement between the grains, and the capacity to store strain energy becomes weaker, corresponding to the plasticity of granite after heat treatment.