Multi-material laser-based powder bed fusion (PBF-LB) allows manufacturing of parts with 3-dimensional gradient and additional functionality in a single step. This research focuses on the combination of thermally-cond...Multi-material laser-based powder bed fusion (PBF-LB) allows manufacturing of parts with 3-dimensional gradient and additional functionality in a single step. This research focuses on the combination of thermally-conductive CuCr1Zr with hard M300 tool steel.Two interface configurations of M300 on CuCr1Zr and CuCr1Zr on M300 were investigated. Ultra-fine grains form at the interface due to the low mutual solubility of Cu and steel. The material mixing zone size is dependent on the configurations and tunable in the range of0.1–0.3 mm by introducing a separate set of parameters for the interface layers. Microcracks and pores mainly occur in the transition zone.Regardless of these defects, the thermal diffusivity of bimetallic parts with 50vol% of CuCr1Zr significantly increases by 70%–150%compared to pure M300. The thermal diffusivity of CuCr1Zr and the hardness of M300 steel can be enhanced simultaneously by applying the aging heat treatment.展开更多
This paper proposes a multi-material topology optimization method based on the hybrid reliability of the probability-ellipsoid model with stress constraint for the stochastic uncertainty and epistemic uncertainty of m...This paper proposes a multi-material topology optimization method based on the hybrid reliability of the probability-ellipsoid model with stress constraint for the stochastic uncertainty and epistemic uncertainty of mechanical loads in optimization design.The probabilistic model is combined with the ellipsoidal model to describe the uncertainty of mechanical loads.The topology optimization formula is combined with the ordered solid isotropic material with penalization(ordered-SIMP)multi-material interpolation model.The stresses of all elements are integrated into a global stress measurement that approximates the maximum stress using the normalized p-norm function.Furthermore,the sequential optimization and reliability assessment(SORA)is applied to transform the original uncertainty optimization problem into an equivalent deterministic topology optimization(DTO)problem.Stochastic response surface and sparse grid technique are combined with SORA to get accurate information on the most probable failure point(MPP).In each cycle,the equivalent topology optimization formula is updated according to the MPP information obtained in the previous cycle.The adjoint variable method is used for deriving the sensitivity of the stress constraint and the moving asymptote method(MMA)is used to update design variables.Finally,the validity and feasibility of the method are verified by the numerical example of L-shape beam design,T-shape structure design,steering knuckle,and 3D T-shaped beam.展开更多
This paper proposes a new element-based multi-material topology optimization algorithm using a single variable for minimizing compliance subject to a mass constraint.A single variable based on the normalized elemental...This paper proposes a new element-based multi-material topology optimization algorithm using a single variable for minimizing compliance subject to a mass constraint.A single variable based on the normalized elemental density is used to overcome the occurrence of meaningless design variables and save computational cost.Different from the traditional material penalization scheme,the algorithm is established on the ordered ersatz material model,which linearly interpolates Young’s modulus for relaxed design variables.To achieve a multi-material design,the multiple floating projection constraints are adopted to gradually push elemental design variables to multiple discrete values.For the convergent element-based solution,the multiple level-set functions are constructed to tentatively extract the smooth interface between two adjacent materials.Some 2D and 3D numerical examples are presented to demonstrate the effectiveness of the proposed algorithm and the possible advantage of the multi-material designs over the traditional solid-void designs.展开更多
In recent years,there has been significant research on the application of deep learning(DL)in topology optimization(TO)to accelerate structural design.However,these methods have primarily focused on solving binary TO ...In recent years,there has been significant research on the application of deep learning(DL)in topology optimization(TO)to accelerate structural design.However,these methods have primarily focused on solving binary TO problems,and effective solutions for multi-material topology optimization(MMTO)which requires a lot of computing resources are still lacking.Therefore,this paper proposes the framework of multiphase topology optimization using deep learning to accelerate MMTO design.The framework employs convolutional neural network(CNN)to construct a surrogate model for solving MMTO,and the obtained surrogate model can rapidly generate multi-material structure topologies in negligible time without any iterations.The performance evaluation results show that the proposed method not only outputs multi-material topologies with clear material boundary but also reduces the calculation cost with high prediction accuracy.Additionally,in order to find a more reasonable modeling method for MMTO,this paper studies the characteristics of surrogate modeling as regression task and classification task.Through the training of 297 models,our findings show that the regression task yields slightly better results than the classification task in most cases.Furthermore,The results indicate that the prediction accuracy is primarily influenced by factors such as the TO problem,material category,and data scale.Conversely,factors such as the domain size and the material property have minimal impact on the accuracy.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
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
Combining the vector level set model,the shape sensitivity analysis theory with the gradient projection technique,a level set method for topology optimization with multi-constraints and multi-materials is presented in...Combining the vector level set model,the shape sensitivity analysis theory with the gradient projection technique,a level set method for topology optimization with multi-constraints and multi-materials is presented in this paper.The method implicitly describes structural material in- terfaces by the vector level set and achieves the optimal shape and topology through the continuous evolution of the material interfaces in the structure.In order to increase computational efficiency for a fast convergence,an appropriate nonlinear speed mapping is established in the tangential space of the active constraints.Meanwhile,in order to overcome the numerical instability of general topology opti- mization problems,the regularization with the mean curvature flow is utilized to maintain the interface smoothness during the optimization process.The numerical examples demonstrate that the approach possesses a good flexibility in handling topological changes and gives an interface representation in a high fidelity,compared with other methods based on explicit boundary variations in the literature.展开更多
In order to mimic the natural heterogeneity of native tissue and provide a better microenvironment for cell culturing,multi-material bioprinting has become a common solution to construct tissue models in vitro.With th...In order to mimic the natural heterogeneity of native tissue and provide a better microenvironment for cell culturing,multi-material bioprinting has become a common solution to construct tissue models in vitro.With the embedded printing method,complex 3D structure can be printed using soft biomaterials with reasonable shape fidelity.However,the current sequential multi-material embedded printing method faces a major challenge,which is the inevitable trade-off between the printed structural integrity and printing precision.Here,we propose a simultaneous multi-material embedded printing method.With this method,we can easily print firmly attached and high-precision multilayer structures.With multiple individually controlled nozzles,different biomaterials can be precisely deposited into a single crevasse,minimizing uncontrolled squeezing and guarantees no contamination of embedding medium within the structure.We analyse the dynamics of the extruded bioink in the embedding medium both analytically and experimentally,and quantitatively evaluate the effects of printing parameters including printing speed and rheology of embedding medium,on the 3D morphology of the printed filament.We demonstrate the printing of double-layer thin-walled structures,each layer less than 200μm,as well as intestine and liver models with 5%gelatin methacryloyl that are crosslinked and extracted from the embedding medium without significant impairment or delamination.The peeling test further proves that the proposed method offers better structural integrity than conventional sequential printing methods.The proposed simultaneous multi-material embedded printing method can serve as a powerful tool to support the complex heterogeneous structure fabrication and open unique prospects for personalized medicine.展开更多
A new design technique for the long life hot forging die has been proposed. By finite element analysis, the reason .for the failure of hot forging die was analyzed and it was concluded that thermal stress is the main ...A new design technique for the long life hot forging die has been proposed. By finite element analysis, the reason .for the failure of hot forging die was analyzed and it was concluded that thermal stress is the main reason for the failure of hot forging die. Based on this conclusion, the whole hot forging die was divided into the substrate part and the heat-resistant part according to the thermal stress distribution. Moreover, the heat-resistant part was further subdivided into more zones and the material of each zone was reasonably selected to ensure that the hot forging die can work in an elastic state. When compared with the existing techniques, this design can greatly increase the service life because the use of multi-materials can alleviate the thermal stress in hot forging die.展开更多
Three-dimensional printing technologies exhibit tremendous potential in the advancing fields of tissue engineering and regenerative medicine due to the precise spatial control over depositing the biomaterial.Despite t...Three-dimensional printing technologies exhibit tremendous potential in the advancing fields of tissue engineering and regenerative medicine due to the precise spatial control over depositing the biomaterial.Despite their widespread utilization and numerous advantages,the development of suitable novel biomaterials for extrusion-based 3D printing of scaffolds that support cell attachment,proliferation,and vascularization remains a challenge.Multi-material composite hydrogels present incredible potential in this field.Thus,in this work,a multi-material composite hydrogel with a promising formulation of chitosan/gelatin functionalized with egg white was developed,which provides good printability and shape fidelity.In addition,a series of comparative analyses of different crosslinking agents and processes based on tripolyphosphate(TPP),genipin(GP),and glutaraldehyde(GTA)were investigated and compared to select the ideal crosslinking strategy to enhance the physicochemical and biological properties of the fabricated scaffolds.All of the results indicate that the composite hydrogel and the resulting scaffolds utilizing TPP crosslinking have great potential in tissue engineering,especially for supporting neo-vessel growth into the scaffold and promoting angiogenesis within engineered tissues.展开更多
Tungsten(W)and stainless steel(SS)are well known for the high melting point and good corrosion resistance respectively.Bimetallic W-SS structures would offer potential applications in extreme environments.In this stud...Tungsten(W)and stainless steel(SS)are well known for the high melting point and good corrosion resistance respectively.Bimetallic W-SS structures would offer potential applications in extreme environments.In this study,a SS→W→SS sandwich structure is fabricated via a special laser powder bed fusion(LPBF)method based on an ultrasonic-assisted powder deposition mechanism.Material characterization of the SS→W interface and W→SS interface was conducted,including microstructure,element distribution,phase distribution,and nano-hardness.A coupled modelling method,combining computational fluid dynamics modelling with discrete element method,simulated the melt pool dynamics and solidification at the material interfaces.The study shows that the interface bonding of SS→W(SS printed on W)is the combined effect of solid-state diffusion with different elemental diffusion rates and grain boundary diffusion.The keyhole mode of the melt pool at the W→SS(W printed on SS)interface makes the pre-printed SS layers repeatedly remelted,causing the liquid W to flow into the sub-surface of the pre-printed SS through the keyhole cavities realizing the bonding of the W→SS interface.The above interfacial bonding behaviours are significantly different from the previously reported bonding mechanism based on the melt pool convection during multiple material LPBF.The abnormal material interfacial bonding behaviours are reported for the first time.展开更多
Sand mold 3 D printing technology is an advanced manufacturing technology which has great flexible manufacturing ability. A multi-material composite sand mold can control the temperature field of metallic parts during...Sand mold 3 D printing technology is an advanced manufacturing technology which has great flexible manufacturing ability. A multi-material composite sand mold can control the temperature field of metallic parts during the pouring process, while the current sand mold 3 D printing technology can only fabricate a single material sand mold. The casting temperature field can not be adjusted by using single sand mold material with isotropous heat exchange ability during the pouring process. In this work, a kind of novel coating device was designed. Multi-material composite sand molds could be manufactured using the coating device according to the casting process demands of the final parts. The influences of curing agent content, coating velocity and scraper shape on compactness and surface roughness of the sand layer(silica sand and zircon sand) were studied. The shapes and sizes of transition intervals of two kinds of sand granules were also tested. The results show that, with the increase of the added volume of curing agent, the compactness of sand layer reduces and the surface roughness value rises. With the increase of the velocity of the coating device, the compactness of sand layer reduces and the surface roughness value rises similarly. In addition, the scraper with a dip angle of 72 degrees could increase the compactness value of the sand layer. The criteria of quality parmeters of the coating procedure are obtained. That is, the surface roughness(δ) of sand layer should be equal to or lesser than half of main size of the sand particles(Dm). The parameter H of the coating device which is the distance between the base of hopper and the surface of sand layer impacts the size of transition zone. The width of the transition zone is in direct proportion to the parameter H, qualitatively. Through the optimization of the coating device, high quality of multi-material sand layers can be obtained. This will provide a solution in manufacturing the multi-material composite sand mold.展开更多
In the paper, the numerical simulation of interface problems for multiple material fluids is studied. The level set function is designed to capture the location of the material interface. For multi-dimensional and mul...In the paper, the numerical simulation of interface problems for multiple material fluids is studied. The level set function is designed to capture the location of the material interface. For multi-dimensional and multi-material fluids, the modified ghost fluid method needs a Riemann solution to renew the variable states near the interface. Here we present a new convenient and effective algorithm for solving the Riemann problem in the normal direction. The extrapolated variables are populated by Taylor series expansions in the direction. The anti-diffusive high order WENO difference scheme with the limiter is adopted for the numerical simulation. Finally we implement a series of numerical experiments of multi-material flows. The obtained results are satisfying, compared to those by other methods.展开更多
This paper presents a robust topology optimization design approach for multi-material functional graded structures under periodic constraint with load uncertainties.To characterize the random-field uncertainties with ...This paper presents a robust topology optimization design approach for multi-material functional graded structures under periodic constraint with load uncertainties.To characterize the random-field uncertainties with a reduced set of random variables,the Karhunen-Lo`eve(K-L)expansion is adopted.The sparse grid numerical integration method is employed to transform the robust topology optimization into a weighted summation of series of deterministic topology optimization.Under dividing the design domain,the volume fraction of each preset gradient layer is extracted.Based on the ordered solid isotropic microstructure with penalization(Ordered-SIMP),a functionally graded multi-material interpolation model is formulated by individually optimizing each preset gradient layer.The periodic constraint setting of the gradient layer is achieved by redistributing the average element compliance in sub-regions.Then,the method of moving asymptotes(MMA)is introduced to iteratively update the design variables.Several numerical examples are presented to verify the validity and applicability of the proposed method.The results demonstrate that the periodic functionally graded multi-material topology can be obtained under different numbers of sub-regions,and robust design structures are more stable than that indicated by the deterministic results.展开更多
基金supported by VTT Technical Research Centre of Finland,Aalto University,Aerosint SA,and partially from European Union Horizon 2020 (No.768775)。
文摘Multi-material laser-based powder bed fusion (PBF-LB) allows manufacturing of parts with 3-dimensional gradient and additional functionality in a single step. This research focuses on the combination of thermally-conductive CuCr1Zr with hard M300 tool steel.Two interface configurations of M300 on CuCr1Zr and CuCr1Zr on M300 were investigated. Ultra-fine grains form at the interface due to the low mutual solubility of Cu and steel. The material mixing zone size is dependent on the configurations and tunable in the range of0.1–0.3 mm by introducing a separate set of parameters for the interface layers. Microcracks and pores mainly occur in the transition zone.Regardless of these defects, the thermal diffusivity of bimetallic parts with 50vol% of CuCr1Zr significantly increases by 70%–150%compared to pure M300. The thermal diffusivity of CuCr1Zr and the hardness of M300 steel can be enhanced simultaneously by applying the aging heat treatment.
基金supported by the National Natural Science Foundation of China(Grant 52175236).
文摘This paper proposes a multi-material topology optimization method based on the hybrid reliability of the probability-ellipsoid model with stress constraint for the stochastic uncertainty and epistemic uncertainty of mechanical loads in optimization design.The probabilistic model is combined with the ellipsoidal model to describe the uncertainty of mechanical loads.The topology optimization formula is combined with the ordered solid isotropic material with penalization(ordered-SIMP)multi-material interpolation model.The stresses of all elements are integrated into a global stress measurement that approximates the maximum stress using the normalized p-norm function.Furthermore,the sequential optimization and reliability assessment(SORA)is applied to transform the original uncertainty optimization problem into an equivalent deterministic topology optimization(DTO)problem.Stochastic response surface and sparse grid technique are combined with SORA to get accurate information on the most probable failure point(MPP).In each cycle,the equivalent topology optimization formula is updated according to the MPP information obtained in the previous cycle.The adjoint variable method is used for deriving the sensitivity of the stress constraint and the moving asymptote method(MMA)is used to update design variables.Finally,the validity and feasibility of the method are verified by the numerical example of L-shape beam design,T-shape structure design,steering knuckle,and 3D T-shaped beam.
基金This work was supported by Hunan Provincial Innovation Foundation for Postgraduate(CX20190278)FJUT Scientific Research Foundation(GY-Z17015)Open Fund of Fujian Key Laboratory of Automotive Electronics and Electric Drive(KF-X19001).
文摘This paper proposes a new element-based multi-material topology optimization algorithm using a single variable for minimizing compliance subject to a mass constraint.A single variable based on the normalized elemental density is used to overcome the occurrence of meaningless design variables and save computational cost.Different from the traditional material penalization scheme,the algorithm is established on the ordered ersatz material model,which linearly interpolates Young’s modulus for relaxed design variables.To achieve a multi-material design,the multiple floating projection constraints are adopted to gradually push elemental design variables to multiple discrete values.For the convergent element-based solution,the multiple level-set functions are constructed to tentatively extract the smooth interface between two adjacent materials.Some 2D and 3D numerical examples are presented to demonstrate the effectiveness of the proposed algorithm and the possible advantage of the multi-material designs over the traditional solid-void designs.
基金supported in part by National Natural Science Foundation of China under Grant Nos.51675525,52005505,and 62001502Post-Graduate Scientific Research Innovation Project of Hunan Province under Grant No.XJCX2023185.
文摘In recent years,there has been significant research on the application of deep learning(DL)in topology optimization(TO)to accelerate structural design.However,these methods have primarily focused on solving binary TO problems,and effective solutions for multi-material topology optimization(MMTO)which requires a lot of computing resources are still lacking.Therefore,this paper proposes the framework of multiphase topology optimization using deep learning to accelerate MMTO design.The framework employs convolutional neural network(CNN)to construct a surrogate model for solving MMTO,and the obtained surrogate model can rapidly generate multi-material structure topologies in negligible time without any iterations.The performance evaluation results show that the proposed method not only outputs multi-material topologies with clear material boundary but also reduces the calculation cost with high prediction accuracy.Additionally,in order to find a more reasonable modeling method for MMTO,this paper studies the characteristics of surrogate modeling as regression task and classification task.Through the training of 297 models,our findings show that the regression task yields slightly better results than the classification task in most cases.Furthermore,The results indicate that the prediction accuracy is primarily influenced by factors such as the TO problem,material category,and data scale.Conversely,factors such as the domain size and the material property have minimal impact on the accuracy.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
基金supported by University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
文摘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The project supported by the National Natural Science Foundation of China (59805001,10332010) and Key Science and Technology Research Project of Ministry of Education of China (No.104060)
文摘Combining the vector level set model,the shape sensitivity analysis theory with the gradient projection technique,a level set method for topology optimization with multi-constraints and multi-materials is presented in this paper.The method implicitly describes structural material in- terfaces by the vector level set and achieves the optimal shape and topology through the continuous evolution of the material interfaces in the structure.In order to increase computational efficiency for a fast convergence,an appropriate nonlinear speed mapping is established in the tangential space of the active constraints.Meanwhile,in order to overcome the numerical instability of general topology opti- mization problems,the regularization with the mean curvature flow is utilized to maintain the interface smoothness during the optimization process.The numerical examples demonstrate that the approach possesses a good flexibility in handling topological changes and gives an interface representation in a high fidelity,compared with other methods based on explicit boundary variations in the literature.
基金the support by National Key Research and Development Program of China(2018YFA0703000)National Natural Science Foundation of China(Grant No.52105310)+1 种基金Natural Science Foundation of Zhejiang Province(Grant No.LDQ23E050001)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(Grant No.SN-ZJU-SIAS-004)。
文摘In order to mimic the natural heterogeneity of native tissue and provide a better microenvironment for cell culturing,multi-material bioprinting has become a common solution to construct tissue models in vitro.With the embedded printing method,complex 3D structure can be printed using soft biomaterials with reasonable shape fidelity.However,the current sequential multi-material embedded printing method faces a major challenge,which is the inevitable trade-off between the printed structural integrity and printing precision.Here,we propose a simultaneous multi-material embedded printing method.With this method,we can easily print firmly attached and high-precision multilayer structures.With multiple individually controlled nozzles,different biomaterials can be precisely deposited into a single crevasse,minimizing uncontrolled squeezing and guarantees no contamination of embedding medium within the structure.We analyse the dynamics of the extruded bioink in the embedding medium both analytically and experimentally,and quantitatively evaluate the effects of printing parameters including printing speed and rheology of embedding medium,on the 3D morphology of the printed filament.We demonstrate the printing of double-layer thin-walled structures,each layer less than 200μm,as well as intestine and liver models with 5%gelatin methacryloyl that are crosslinked and extracted from the embedding medium without significant impairment or delamination.The peeling test further proves that the proposed method offers better structural integrity than conventional sequential printing methods.The proposed simultaneous multi-material embedded printing method can serve as a powerful tool to support the complex heterogeneous structure fabrication and open unique prospects for personalized medicine.
基金the National Natural Science Foundation of China (No. 50675165).
文摘A new design technique for the long life hot forging die has been proposed. By finite element analysis, the reason .for the failure of hot forging die was analyzed and it was concluded that thermal stress is the main reason for the failure of hot forging die. Based on this conclusion, the whole hot forging die was divided into the substrate part and the heat-resistant part according to the thermal stress distribution. Moreover, the heat-resistant part was further subdivided into more zones and the material of each zone was reasonably selected to ensure that the hot forging die can work in an elastic state. When compared with the existing techniques, this design can greatly increase the service life because the use of multi-materials can alleviate the thermal stress in hot forging die.
基金The authors acknowledge the funding support from the National Natural Science Foundation of China(Nos.52175474 and 51775324)the China Scholarship Council(No.202006890054).
文摘Three-dimensional printing technologies exhibit tremendous potential in the advancing fields of tissue engineering and regenerative medicine due to the precise spatial control over depositing the biomaterial.Despite their widespread utilization and numerous advantages,the development of suitable novel biomaterials for extrusion-based 3D printing of scaffolds that support cell attachment,proliferation,and vascularization remains a challenge.Multi-material composite hydrogels present incredible potential in this field.Thus,in this work,a multi-material composite hydrogel with a promising formulation of chitosan/gelatin functionalized with egg white was developed,which provides good printability and shape fidelity.In addition,a series of comparative analyses of different crosslinking agents and processes based on tripolyphosphate(TPP),genipin(GP),and glutaraldehyde(GTA)were investigated and compared to select the ideal crosslinking strategy to enhance the physicochemical and biological properties of the fabricated scaffolds.All of the results indicate that the composite hydrogel and the resulting scaffolds utilizing TPP crosslinking have great potential in tissue engineering,especially for supporting neo-vessel growth into the scaffold and promoting angiogenesis within engineered tissues.
基金funded by the Engineering and Physical Science Research Council(EPSRC),UK(Grant Nos.EP/P027563/1 and EP/M028267/1)the Science and Technology Facilities Council(STFC)(Grant No.ST/R006105/1)the Bridging for Innovators Programme of Department for Business,Energy and Industrial Strategy(BEIS),UK.
文摘Tungsten(W)and stainless steel(SS)are well known for the high melting point and good corrosion resistance respectively.Bimetallic W-SS structures would offer potential applications in extreme environments.In this study,a SS→W→SS sandwich structure is fabricated via a special laser powder bed fusion(LPBF)method based on an ultrasonic-assisted powder deposition mechanism.Material characterization of the SS→W interface and W→SS interface was conducted,including microstructure,element distribution,phase distribution,and nano-hardness.A coupled modelling method,combining computational fluid dynamics modelling with discrete element method,simulated the melt pool dynamics and solidification at the material interfaces.The study shows that the interface bonding of SS→W(SS printed on W)is the combined effect of solid-state diffusion with different elemental diffusion rates and grain boundary diffusion.The keyhole mode of the melt pool at the W→SS(W printed on SS)interface makes the pre-printed SS layers repeatedly remelted,causing the liquid W to flow into the sub-surface of the pre-printed SS through the keyhole cavities realizing the bonding of the W→SS interface.The above interfacial bonding behaviours are significantly different from the previously reported bonding mechanism based on the melt pool convection during multiple material LPBF.The abnormal material interfacial bonding behaviours are reported for the first time.
基金financially supported by the National Excellent Young Scientists Fund(NO.51525503)
文摘Sand mold 3 D printing technology is an advanced manufacturing technology which has great flexible manufacturing ability. A multi-material composite sand mold can control the temperature field of metallic parts during the pouring process, while the current sand mold 3 D printing technology can only fabricate a single material sand mold. The casting temperature field can not be adjusted by using single sand mold material with isotropous heat exchange ability during the pouring process. In this work, a kind of novel coating device was designed. Multi-material composite sand molds could be manufactured using the coating device according to the casting process demands of the final parts. The influences of curing agent content, coating velocity and scraper shape on compactness and surface roughness of the sand layer(silica sand and zircon sand) were studied. The shapes and sizes of transition intervals of two kinds of sand granules were also tested. The results show that, with the increase of the added volume of curing agent, the compactness of sand layer reduces and the surface roughness value rises. With the increase of the velocity of the coating device, the compactness of sand layer reduces and the surface roughness value rises similarly. In addition, the scraper with a dip angle of 72 degrees could increase the compactness value of the sand layer. The criteria of quality parmeters of the coating procedure are obtained. That is, the surface roughness(δ) of sand layer should be equal to or lesser than half of main size of the sand particles(Dm). The parameter H of the coating device which is the distance between the base of hopper and the surface of sand layer impacts the size of transition zone. The width of the transition zone is in direct proportion to the parameter H, qualitatively. Through the optimization of the coating device, high quality of multi-material sand layers can be obtained. This will provide a solution in manufacturing the multi-material composite sand mold.
文摘In the paper, the numerical simulation of interface problems for multiple material fluids is studied. The level set function is designed to capture the location of the material interface. For multi-dimensional and multi-material fluids, the modified ghost fluid method needs a Riemann solution to renew the variable states near the interface. Here we present a new convenient and effective algorithm for solving the Riemann problem in the normal direction. The extrapolated variables are populated by Taylor series expansions in the direction. The anti-diffusive high order WENO difference scheme with the limiter is adopted for the numerical simulation. Finally we implement a series of numerical experiments of multi-material flows. The obtained results are satisfying, compared to those by other methods.
基金This work is supported by the Natural Science Foundation of China(Grant 51705268)China Postdoctoral Science Foundation Funded Project(Grant 2017M612191).
文摘This paper presents a robust topology optimization design approach for multi-material functional graded structures under periodic constraint with load uncertainties.To characterize the random-field uncertainties with a reduced set of random variables,the Karhunen-Lo`eve(K-L)expansion is adopted.The sparse grid numerical integration method is employed to transform the robust topology optimization into a weighted summation of series of deterministic topology optimization.Under dividing the design domain,the volume fraction of each preset gradient layer is extracted.Based on the ordered solid isotropic microstructure with penalization(Ordered-SIMP),a functionally graded multi-material interpolation model is formulated by individually optimizing each preset gradient layer.The periodic constraint setting of the gradient layer is achieved by redistributing the average element compliance in sub-regions.Then,the method of moving asymptotes(MMA)is introduced to iteratively update the design variables.Several numerical examples are presented to verify the validity and applicability of the proposed method.The results demonstrate that the periodic functionally graded multi-material topology can be obtained under different numbers of sub-regions,and robust design structures are more stable than that indicated by the deterministic results.