Geomaterials with inferior hydraulic and strength characteristics often need improvement to enhance their engineering behaviors.Traditional ground improvement techniques require enormous mechanical effort or synthetic...Geomaterials with inferior hydraulic and strength characteristics often need improvement to enhance their engineering behaviors.Traditional ground improvement techniques require enormous mechanical effort or synthetic chemicals.Sustainable stabilization technique such as microbially induced calcite precipitation(MICP)utilizes bacterial metabolic processes to precipitate cementitious calcium carbonate.The reactive transport of biochemical species in the soil mass initiates the precipitation of biocement during the MICP process.The precipitated biocement alters the hydro-mechanical performance of the soil mass.Usually,the flow,deformation,and transport phenomena regulate the biocementation technique via coupled bio-chemo-hydro-mechanical(BCHM)processes.Among all,one crucial phenomenon controlling the precipitation mechanism is the encapsulation of biomass by calcium carbonate.Biomass encapsulation can potentially reduce the biochemical reaction rate and decelerate biocementation.Laboratory examination of the encapsulation process demands a thorough analysis of associated coupled effects.Despite this,a numerical model can assist in capturing the coupled processes influencing encapsulation during the MICP treatment.However,most numerical models did not consider biochemical reaction rate kinetics accounting for the influence of bacterial encapsulation.Given this,the current study developed a coupled BCHM model to evaluate the effect of encapsulation on the precipitated calcite content using a micro-scale semiempirical relationship.Firstly,the developed BCHM model was verified and validated using numerical and experimental observations of soil column tests.Later,the encapsulation phenomenon was investigated in the soil columns of variable maximum calcite crystal sizes.The results depict altered reaction rates due to the encapsulation phenomenon and an observable change in the precipitated calcite content for each maximum crystal size.Furthermore,the permeability and deformation of the soil mass were affected by the simultaneous precipitation of calcium carbonate.Overall,the present study comprehended the influence of the encapsulation of bacteria on cement morphology-induced permeability,biocement-induced stresses and displacements.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
In the context of deepening educational reforms,the significance of ideological and political education has become increasingly prominent,emerging as a crucial aspect of enhancing students’comprehensive qualities.To ...In the context of deepening educational reforms,the significance of ideological and political education has become increasingly prominent,emerging as a crucial aspect of enhancing students’comprehensive qualities.To ensure the orderly progress of ideological and political education in courses,it is essential to actively promote the integration of ideological and political elements within coursework.This integration aims to align professional course education with ideological and political education,fostering a collaborative educational model.Therefore,in the teaching of bidding and contract management courses,constructing a“micro-ideological and political”teaching model has emerged as a critical component.The implementation of this model facilitates the seamless integration of bidding and contract management coursework with ideological and political education,thereby elevating the teaching quality of these courses.Additionally,it leverages the synergistic role of coursework and ideology in educating students,ultimately enhancing the quality and level of talent cultivation.Hence,this paper proposes strategies for constructing a“microideological and political”model within the context of ideological and political teaching reforms in bidding and contract management courses,inviting discussion and exchange on this topic.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 inherent mechanism of size effect in micro-sheet material behavior of plastic forming was explained by the surface layer model and theory of metal crystal plasticity. A size-dependant constitutive model based on t...The inherent mechanism of size effect in micro-sheet material behavior of plastic forming was explained by the surface layer model and theory of metal crystal plasticity. A size-dependant constitutive model based on the surface layer model was established by introducing the scale parameters and modifying the classical Hall-Petch equation. The influence of the geometric dimensions and the grain size on the flow behavior of the material was discussed using the new material constitutive model. The results show that, the flow stress decreases while the sheet metal thickness decreases when the grain size keeps constant, and the micro-sheet metal with a larger grain size is more easily to be influenced by the size effects. The material constitutive model established is validated by the stress-strain curve of the micro-sheet metal with different thicknesses derived from the tensile experiments. The rationality of the material model is verified by the fact that the calculation results are consistent with the experimental results.展开更多
Effects of four factors on thin sheet metal flow stress were considered, including grain size d, thickness t, grain number across thickness (t/d ratio) and surface property. Surface model was adopted to quantitative...Effects of four factors on thin sheet metal flow stress were considered, including grain size d, thickness t, grain number across thickness (t/d ratio) and surface property. Surface model was adopted to quantitatively describe the effect of t/d ratio on flow stress for pure copper. It is predicted that when t/d ratio is larger than a critical value, effect of t/d ratio on flow stress can be neglected. Existence of critical t/d ratio changes the Hall-Petch relationship and evolution of flow stress with thickness. A criterion was proposed to determine critical t/d ratio. Then a comprehensive constitutive model was developed to consider all the four factors, with parameters determined by fitting experimental data of high purity Ni. The predicted results show the same tendencies with experiment results. Particularly when t/d ratio decreases, Hall-Petch relationship and evolution of true stress show varied slopes with two transition points.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
Micro-tubes manufactured by hydro-forming techniques have now been widely used in medical and microelectronics applica- tions. One of the difficulties in forming such parts is the control of localized necking in the i...Micro-tubes manufactured by hydro-forming techniques have now been widely used in medical and microelectronics applica- tions. One of the difficulties in forming such parts is the control of localized necking in the initial stages of the deformation/forming process. A lack of microstructural information causes conventional macro-mechanics finite element(FE) tools to break down when used to investigate the localized microstructure evolution and necking encountered in micro-forming. An effort has been made to create an integrated crystal plasticity finite element(CPFE) system that enables micro-forming process simulations to be carried out easily, with the important features in forming micro-parts captured by the model. Based on Voronoi tessellation and probability theory, a virtual GRAIN(VGRAIN) system is created for generating grains and grain boundaries for micro-materials. Numerical procedures are devel- oped to link the physical parameters of a material to the control variables in a Gamma distribution. A script interface is developed so that the virtual microstructure can be input to the commercial FE code, ABAQUS, for mesh generation. A simplified plane strain CPFE modeling technique is developed and used to capture localized thinning and failure features for hydro-forming of micro-tubes. Grains within the tube workpiece, their distributions and orientations are generated automatically by using the VGRAIN system. A set of crystal viscoplasticity constitutive equations are implemented in ABAQUS/Explicit by using the user-defined material subroutine, VUMAT. Lo- calized thinning is analyzed for different microstructures and deformation conditions of the material using the CPFE modeling technique. The research results show that locations of thinning in forming micro-tubes can be random, which are related to microstructure and grain orientations of the material. The proposed CPFE technique can be used to predict the locations of thinning in forming micro-tubes.展开更多
A two phase model of rock was proposed in order to investigate the mechanism of brittle fracture due to uniaxial compression, in which rock was considered to be a composite material consisting of hard grains and collo...A two phase model of rock was proposed in order to investigate the mechanism of brittle fracture due to uniaxial compression, in which rock was considered to be a composite material consisting of hard grains and colloids. The stress state in colloid region near grains was calculated using Finite Element Method (FEM). The influence of the tensile stresses on the crack initiation and failure process of brittle rock subjected to uniaxial compression was investigated by numerical experiments. The FE results show that tensile stresses are induced easily in the neighboring area of hard grains with the maximum value near grain boundaries. The distribution of tensile stresses depends on the relative position of hard grains. The cracks initiated just near the boundary area of hard grains, which was governed by tensile stress. These results clearly reveal the micro fracture mechanism of brittle rock loaded by uniaxial compression. It can be concluded that the failure mode of brittle rock under uniaxial compression is still tensile fracture from the point view of microstructure. However, since the wide colloid region is still under compressive stress state, further propagation of boundary cracks through this region obviously needs more external load, thus causing the uniaxial compressive strength of rock much higher than its tensile strength obtained via Brazilian (splitting)展开更多
A micro-layer model is proposed to account for the lubrication effect of liquid layer near collisions of immersed particles at moderate particle Reynolds number.This new model is to allow determination of the pressure...A micro-layer model is proposed to account for the lubrication effect of liquid layer near collisions of immersed particles at moderate particle Reynolds number.This new model is to allow determination of the pressure profile within the micro-layer including the fluid inertia and viscosity.Then a correction based on the micro-layer model is applied to unsteady 3-D direct simulation of a particle approaching another one.The simulation is based on a modified immersed boundary method with direct force scheme.The quantitative agreement between numerical and experimental results validates the model presented in the study.The simulation results show that the fluid is squeezed prior to contact.When a particle approaches a flat wall or another particle,the lubrication force,obtained by integrating the pressure profile over the particle surface,is increased and prevents the particle from approaching.The model predicts that the velocity of approaching particle starts to decrease when separation distance of particles is less than 0.1dp,where dp is the particle diameter.展开更多
A grain-based distinct element model featuring three-dimensional (3D) Voronoi tessellations (randompoly-crystals) is proposed for simulation of crack damage development in brittle rocks. The grainboundaries in pol...A grain-based distinct element model featuring three-dimensional (3D) Voronoi tessellations (randompoly-crystals) is proposed for simulation of crack damage development in brittle rocks. The grainboundaries in poly-crystal structure produced by Voronoi tessellations can represent flaws in intact rockand allow for numerical replication of crack damage progression through initiation and propagation ofmicro-fractures along grain boundaries. The Voronoi modelling scheme has been used widely in the pastfor brittle fracture simulation of rock materials. However the difficulty of generating 3D Voronoi modelshas limited its application to two-dimensional (2D) codes. The proposed approach is implemented inNeper, an open-source engine for generation of 3D Voronoi grains, to generate block geometry files thatcan be read directly into 3DEC. A series of Unconfined Compressive Strength (UCS) tests are simulated in3DEC to verify the proposed methodology for 3D simulation of brittle fractures and to investigate therelationship between each micro-parameter and the model's macro-response. The possibility of numericalreplication of the classical U-shape strength curve for anisotropic rocks is also investigated innumerical UCS tests by using complex-shaped (elongated) grains that are cemented to one another alongtheir adjoining sides. A micro-parameter calibration procedure is established for 3D Voronoi models foraccurate replication of the mechanical behaviour of isotropic and anisotropic (containing a fabric) rocks. 2014 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.展开更多
Effects of time-dependent deformation(TDD) on a tunnel constructed using the micro-tunneling technique in Queenston shale(QS) are investigated employing the finite element method. The TDD and strength parameters o...Effects of time-dependent deformation(TDD) on a tunnel constructed using the micro-tunneling technique in Queenston shale(QS) are investigated employing the finite element method. The TDD and strength parameters of the QS were measured from tests conducted on QS specimens soaked in water and lubricant fluids(LFs) used in micro-tunneling such as bentonite and polymer solutions. The numerical model was verified using the results of TDD tests performed on QS samples, field measurements of some documented projects, and the closed-form solutions to circular tunnels in swelling rock. The verified model was then employed to conduct a parametric study considering important micro-tunneling design parameters, such as depth and diameter of the tunnel, in situ stress ratio(K;), and the time lapse prior to replacing LFs with permanent cement grout around the tunnel. It was revealed that the time lapse plays a vital role in controlling deformations and associated stresses developed in the tunnel lining.The critical case of a pipe or tunnel in which the maximum tensile stress develops at its springline occurs when it is constructed at shallow depths in the QS layer. The results of the parametric study were used to suggest recommendations for the construction of tunnels in QS employing micro-tunneling.展开更多
To aim at prototype parts fabricated with fused deposition modeling (FDM) process, the problems how to improve and enhance their surface micro-precision are studied. The producing mechanism of surface roughness is e...To aim at prototype parts fabricated with fused deposition modeling (FDM) process, the problems how to improve and enhance their surface micro-precision are studied. The producing mechanism of surface roughness is explained with three aspects concretely including the principle error of rapid prototyping (RP) process, the inherent characteristics of FDM process, and some mi- cro-scratches on the surface of the extruded fiber. Based on the micro-characters of section shape of the FDM prototype, a physical model reflecting the outer shape characters is abstracted. With the physical simplified and deduced, the evaluating equations of surface roughness are acquired. According to the FDM sample parts with special design for experimental measurement, the real surface roughness values of different inclined planes are obtained. And the measuring values of surface roughness are compared with the calculation values. Furthermore, the causes of surface roughness deviation between measuring values and calculation values are respectively analyzed and studied. With the references of analytic conclusions, the measuring values of the experimental part surface are revised, and the revised values nearly accord with the calculation values. Based on the influencing principles of FDM process parameters and special post processing of FDM prototype parts, some concrete measures are proposed to reduce the surface roughness of FDM parts, and the applying effects are better.展开更多
Ship hull form of the underwater area strongly influences the resistance of the ship. The major factor in ship resistance is skin friction resistance. Bulbous bows, polymer paint, water repellent paint (highly water-...Ship hull form of the underwater area strongly influences the resistance of the ship. The major factor in ship resistance is skin friction resistance. Bulbous bows, polymer paint, water repellent paint (highly water-repellent wall), air injection, and specific roughness have been used by researchers as an attempt to obtain the resistance reduction and operation efficiency of ships. Micro-bubble injection is a promising technique for lowering frictional resistance. The injected air bubbles are supposed to somehow modify the energy inside the turbulent boundary layer and thereby lower the skin friction. The purpose of this study was to identify the effect of injected micro bubbles on a navy fast patrol boat (FPB) 57 m type model with the following main dimensions: L=2 450 ram, B=400 mm, and T=190 mm. The influence of the location of micro bubble injection and bubble velocity was also investigated. The ship model was pulled by an electric motor whose speed could be varied and adjusted. The ship model resistance was precisely measured by a load cell transducer. Comparison of ship resistance with and without micro-bubble injection was shown on a graph as a function of the drag coefficient and Froude number. It was shown that micro bubble injection behind the mid-ship is the best location to achieve the most effective drag reduction, and the drag reduction caused by the micro-bubbles can reach 6%-9%.展开更多
基金the funding support from the Ministry of Education,Government of India,under the Prime Minister Research Fellowship programme(Grant Nos.SB21221901CEPMRF008347 and SB22230217CEPMRF008347).
文摘Geomaterials with inferior hydraulic and strength characteristics often need improvement to enhance their engineering behaviors.Traditional ground improvement techniques require enormous mechanical effort or synthetic chemicals.Sustainable stabilization technique such as microbially induced calcite precipitation(MICP)utilizes bacterial metabolic processes to precipitate cementitious calcium carbonate.The reactive transport of biochemical species in the soil mass initiates the precipitation of biocement during the MICP process.The precipitated biocement alters the hydro-mechanical performance of the soil mass.Usually,the flow,deformation,and transport phenomena regulate the biocementation technique via coupled bio-chemo-hydro-mechanical(BCHM)processes.Among all,one crucial phenomenon controlling the precipitation mechanism is the encapsulation of biomass by calcium carbonate.Biomass encapsulation can potentially reduce the biochemical reaction rate and decelerate biocementation.Laboratory examination of the encapsulation process demands a thorough analysis of associated coupled effects.Despite this,a numerical model can assist in capturing the coupled processes influencing encapsulation during the MICP treatment.However,most numerical models did not consider biochemical reaction rate kinetics accounting for the influence of bacterial encapsulation.Given this,the current study developed a coupled BCHM model to evaluate the effect of encapsulation on the precipitated calcite content using a micro-scale semiempirical relationship.Firstly,the developed BCHM model was verified and validated using numerical and experimental observations of soil column tests.Later,the encapsulation phenomenon was investigated in the soil columns of variable maximum calcite crystal sizes.The results depict altered reaction rates due to the encapsulation phenomenon and an observable change in the precipitated calcite content for each maximum crystal size.Furthermore,the permeability and deformation of the soil mass were affected by the simultaneous precipitation of calcium carbonate.Overall,the present study comprehended the influence of the encapsulation of bacteria on cement morphology-induced permeability,biocement-induced stresses and displacements.
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.
文摘In the context of deepening educational reforms,the significance of ideological and political education has become increasingly prominent,emerging as a crucial aspect of enhancing students’comprehensive qualities.To ensure the orderly progress of ideological and political education in courses,it is essential to actively promote the integration of ideological and political elements within coursework.This integration aims to align professional course education with ideological and political education,fostering a collaborative educational model.Therefore,in the teaching of bidding and contract management courses,constructing a“micro-ideological and political”teaching model has emerged as a critical component.The implementation of this model facilitates the seamless integration of bidding and contract management coursework with ideological and political education,thereby elevating the teaching quality of these courses.Additionally,it leverages the synergistic role of coursework and ideology in educating students,ultimately enhancing the quality and level of talent cultivation.Hence,this paper proposes strategies for constructing a“microideological and political”model within the context of ideological and political teaching reforms in bidding and contract management courses,inviting discussion and exchange on this topic.
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Project(50975163)supported by the National Natural Science Foundation of ChinaProject(IRT0931)supported by Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China
文摘The inherent mechanism of size effect in micro-sheet material behavior of plastic forming was explained by the surface layer model and theory of metal crystal plasticity. A size-dependant constitutive model based on the surface layer model was established by introducing the scale parameters and modifying the classical Hall-Petch equation. The influence of the geometric dimensions and the grain size on the flow behavior of the material was discussed using the new material constitutive model. The results show that, the flow stress decreases while the sheet metal thickness decreases when the grain size keeps constant, and the micro-sheet metal with a larger grain size is more easily to be influenced by the size effects. The material constitutive model established is validated by the stress-strain curve of the micro-sheet metal with different thicknesses derived from the tensile experiments. The rationality of the material model is verified by the fact that the calculation results are consistent with the experimental results.
基金Projects(50835002,50975174,50821003)supported by the National Natural Science Foundation of ChinaProjects(200802480053,20100073110044)supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China
文摘Effects of four factors on thin sheet metal flow stress were considered, including grain size d, thickness t, grain number across thickness (t/d ratio) and surface property. Surface model was adopted to quantitatively describe the effect of t/d ratio on flow stress for pure copper. It is predicted that when t/d ratio is larger than a critical value, effect of t/d ratio on flow stress can be neglected. Existence of critical t/d ratio changes the Hall-Petch relationship and evolution of flow stress with thickness. A criterion was proposed to determine critical t/d ratio. Then a comprehensive constitutive model was developed to consider all the four factors, with parameters determined by fitting experimental data of high purity Ni. The predicted results show the same tendencies with experiment results. Particularly when t/d ratio decreases, Hall-Petch relationship and evolution of true stress show varied slopes with two transition points.
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 EuropeanFP6-IP Project"Integration of Manufacturing Systems for Mass-manufacture of Miniature/Micro-Products(MASMICRO)"
文摘Micro-tubes manufactured by hydro-forming techniques have now been widely used in medical and microelectronics applica- tions. One of the difficulties in forming such parts is the control of localized necking in the initial stages of the deformation/forming process. A lack of microstructural information causes conventional macro-mechanics finite element(FE) tools to break down when used to investigate the localized microstructure evolution and necking encountered in micro-forming. An effort has been made to create an integrated crystal plasticity finite element(CPFE) system that enables micro-forming process simulations to be carried out easily, with the important features in forming micro-parts captured by the model. Based on Voronoi tessellation and probability theory, a virtual GRAIN(VGRAIN) system is created for generating grains and grain boundaries for micro-materials. Numerical procedures are devel- oped to link the physical parameters of a material to the control variables in a Gamma distribution. A script interface is developed so that the virtual microstructure can be input to the commercial FE code, ABAQUS, for mesh generation. A simplified plane strain CPFE modeling technique is developed and used to capture localized thinning and failure features for hydro-forming of micro-tubes. Grains within the tube workpiece, their distributions and orientations are generated automatically by using the VGRAIN system. A set of crystal viscoplasticity constitutive equations are implemented in ABAQUS/Explicit by using the user-defined material subroutine, VUMAT. Lo- calized thinning is analyzed for different microstructures and deformation conditions of the material using the CPFE modeling technique. The research results show that locations of thinning in forming micro-tubes can be random, which are related to microstructure and grain orientations of the material. The proposed CPFE technique can be used to predict the locations of thinning in forming micro-tubes.
文摘A two phase model of rock was proposed in order to investigate the mechanism of brittle fracture due to uniaxial compression, in which rock was considered to be a composite material consisting of hard grains and colloids. The stress state in colloid region near grains was calculated using Finite Element Method (FEM). The influence of the tensile stresses on the crack initiation and failure process of brittle rock subjected to uniaxial compression was investigated by numerical experiments. The FE results show that tensile stresses are induced easily in the neighboring area of hard grains with the maximum value near grain boundaries. The distribution of tensile stresses depends on the relative position of hard grains. The cracks initiated just near the boundary area of hard grains, which was governed by tensile stress. These results clearly reveal the micro fracture mechanism of brittle rock loaded by uniaxial compression. It can be concluded that the failure mode of brittle rock under uniaxial compression is still tensile fracture from the point view of microstructure. However, since the wide colloid region is still under compressive stress state, further propagation of boundary cracks through this region obviously needs more external load, thus causing the uniaxial compressive strength of rock much higher than its tensile strength obtained via Brazilian (splitting)
文摘A micro-layer model is proposed to account for the lubrication effect of liquid layer near collisions of immersed particles at moderate particle Reynolds number.This new model is to allow determination of the pressure profile within the micro-layer including the fluid inertia and viscosity.Then a correction based on the micro-layer model is applied to unsteady 3-D direct simulation of a particle approaching another one.The simulation is based on a modified immersed boundary method with direct force scheme.The quantitative agreement between numerical and experimental results validates the model presented in the study.The simulation results show that the fluid is squeezed prior to contact.When a particle approaches a flat wall or another particle,the lubrication force,obtained by integrating the pressure profile over the particle surface,is increased and prevents the particle from approaching.The model predicts that the velocity of approaching particle starts to decrease when separation distance of particles is less than 0.1dp,where dp is the particle diameter.
文摘A grain-based distinct element model featuring three-dimensional (3D) Voronoi tessellations (randompoly-crystals) is proposed for simulation of crack damage development in brittle rocks. The grainboundaries in poly-crystal structure produced by Voronoi tessellations can represent flaws in intact rockand allow for numerical replication of crack damage progression through initiation and propagation ofmicro-fractures along grain boundaries. The Voronoi modelling scheme has been used widely in the pastfor brittle fracture simulation of rock materials. However the difficulty of generating 3D Voronoi modelshas limited its application to two-dimensional (2D) codes. The proposed approach is implemented inNeper, an open-source engine for generation of 3D Voronoi grains, to generate block geometry files thatcan be read directly into 3DEC. A series of Unconfined Compressive Strength (UCS) tests are simulated in3DEC to verify the proposed methodology for 3D simulation of brittle fractures and to investigate therelationship between each micro-parameter and the model's macro-response. The possibility of numericalreplication of the classical U-shape strength curve for anisotropic rocks is also investigated innumerical UCS tests by using complex-shaped (elongated) grains that are cemented to one another alongtheir adjoining sides. A micro-parameter calibration procedure is established for 3D Voronoi models foraccurate replication of the mechanical behaviour of isotropic and anisotropic (containing a fabric) rocks. 2014 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.
基金Ward and Burke Microtunneling Ltd. for its excellent technical and financial support
文摘Effects of time-dependent deformation(TDD) on a tunnel constructed using the micro-tunneling technique in Queenston shale(QS) are investigated employing the finite element method. The TDD and strength parameters of the QS were measured from tests conducted on QS specimens soaked in water and lubricant fluids(LFs) used in micro-tunneling such as bentonite and polymer solutions. The numerical model was verified using the results of TDD tests performed on QS samples, field measurements of some documented projects, and the closed-form solutions to circular tunnels in swelling rock. The verified model was then employed to conduct a parametric study considering important micro-tunneling design parameters, such as depth and diameter of the tunnel, in situ stress ratio(K;), and the time lapse prior to replacing LFs with permanent cement grout around the tunnel. It was revealed that the time lapse plays a vital role in controlling deformations and associated stresses developed in the tunnel lining.The critical case of a pipe or tunnel in which the maximum tensile stress develops at its springline occurs when it is constructed at shallow depths in the QS layer. The results of the parametric study were used to suggest recommendations for the construction of tunnels in QS employing micro-tunneling.
基金supported by National Natural Science Foundation of China(61374055)Natural Science Foundation of Jiangsu Province(BK20131381)+3 种基金China Postdoctoral Science Foundation funded project(2013M541663)Jiangsu Planned Projects for Postdoctoral Research Funds(1202015C)Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(BJ213022)Scientific Research Foundation of Nanjing University of Posts and Telecommunications(NY214075,XJKY14004)
基金This project is supported by National Natural Science Foundation of China (No. 50575139)
文摘To aim at prototype parts fabricated with fused deposition modeling (FDM) process, the problems how to improve and enhance their surface micro-precision are studied. The producing mechanism of surface roughness is explained with three aspects concretely including the principle error of rapid prototyping (RP) process, the inherent characteristics of FDM process, and some mi- cro-scratches on the surface of the extruded fiber. Based on the micro-characters of section shape of the FDM prototype, a physical model reflecting the outer shape characters is abstracted. With the physical simplified and deduced, the evaluating equations of surface roughness are acquired. According to the FDM sample parts with special design for experimental measurement, the real surface roughness values of different inclined planes are obtained. And the measuring values of surface roughness are compared with the calculation values. Furthermore, the causes of surface roughness deviation between measuring values and calculation values are respectively analyzed and studied. With the references of analytic conclusions, the measuring values of the experimental part surface are revised, and the revised values nearly accord with the calculation values. Based on the influencing principles of FDM process parameters and special post processing of FDM prototype parts, some concrete measures are proposed to reduce the surface roughness of FDM parts, and the applying effects are better.
基金Supported by the Directorate for Research and Community Service,University of Indonesia(RUUI Research Laboratory 2010),Jakarta,Indonesia
文摘Ship hull form of the underwater area strongly influences the resistance of the ship. The major factor in ship resistance is skin friction resistance. Bulbous bows, polymer paint, water repellent paint (highly water-repellent wall), air injection, and specific roughness have been used by researchers as an attempt to obtain the resistance reduction and operation efficiency of ships. Micro-bubble injection is a promising technique for lowering frictional resistance. The injected air bubbles are supposed to somehow modify the energy inside the turbulent boundary layer and thereby lower the skin friction. The purpose of this study was to identify the effect of injected micro bubbles on a navy fast patrol boat (FPB) 57 m type model with the following main dimensions: L=2 450 ram, B=400 mm, and T=190 mm. The influence of the location of micro bubble injection and bubble velocity was also investigated. The ship model was pulled by an electric motor whose speed could be varied and adjusted. The ship model resistance was precisely measured by a load cell transducer. Comparison of ship resistance with and without micro-bubble injection was shown on a graph as a function of the drag coefficient and Froude number. It was shown that micro bubble injection behind the mid-ship is the best location to achieve the most effective drag reduction, and the drag reduction caused by the micro-bubbles can reach 6%-9%.