To equip data-driven dynamic chemical process models with strong interpretability,we develop a light attention–convolution–gate recurrent unit(LACG)architecture with three sub-modules—a basic module,a brand-new lig...To equip data-driven dynamic chemical process models with strong interpretability,we develop a light attention–convolution–gate recurrent unit(LACG)architecture with three sub-modules—a basic module,a brand-new light attention module,and a residue module—that are specially designed to learn the general dynamic behavior,transient disturbances,and other input factors of chemical processes,respectively.Combined with a hyperparameter optimization framework,Optuna,the effectiveness of the proposed LACG is tested by distributed control system data-driven modeling experiments on the discharge flowrate of an actual deethanization process.The LACG model provides significant advantages in prediction accuracy and model generalization compared with other models,including the feedforward neural network,convolution neural network,long short-term memory(LSTM),and attention-LSTM.Moreover,compared with the simulation results of a deethanization model built using Aspen Plus Dynamics V12.1,the LACG parameters are demonstrated to be interpretable,and more details on the variable interactions can be observed from the model parameters in comparison with the traditional interpretable model attention-LSTM.This contribution enriches interpretable machine learning knowledge and provides a reliable method with high accuracy for actual chemical process modeling,paving a route to intelligent manufacturing.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
To validate the potential space-time adaptive processing (STAP) algorithms for airborne bistatic radar clutter suppression under nonstationary and non-Gaussian clutter environments, a statistically non-Gaussian, spa...To validate the potential space-time adaptive processing (STAP) algorithms for airborne bistatic radar clutter suppression under nonstationary and non-Gaussian clutter environments, a statistically non-Gaussian, space-time clutter model in varying bistatic geometrical scenarios is presented. The inclusive effects of the model contain the range dependency of bistatic clutter spectrum and clutter power variation in range-angle cells. To capture them, a new approach to coordinate system conversion is initiated into formulating bistatic geometrical model, and the bistatic non-Gaussian amplitude clutter representation method based on a compound model is introduced. The veracity of the geometrical model is validated by using the bistatic configuration parameters of multi-channel airborne radar measurement (MCARM) experiment. And simulation results manifest that the proposed model can accurately shape the space-time clutter spectrum tied up with specific airborne bistatic radar scenario and can characterize the heterogeneity of clutter amplitude distribution in practical clutter environments.展开更多
In this paper, we have introduced a shell-model of Kraichnan's passive scalar problem. Different from the original problem, the prescribed random velocity field is non-Gaussian and σ correlated in time, and its intr...In this paper, we have introduced a shell-model of Kraichnan's passive scalar problem. Different from the original problem, the prescribed random velocity field is non-Gaussian and σ correlated in time, and its introduction is inspired by She and Levveque (Phys. Rev. Lett. 72, 336 (1994)). For comparison, we also give the passive scalar advected by the Gaussian random velocity field. The anomalous scaling exponents H(p) of passive scalar advected by these two kinds of random velocities above are determined for structure function with values of p up to 15 by Monte Carlo simulations of the random shell model, with Gear methods used to solve the stochastic differential equations. We find that the H(p) advected by the non-Gaussian random velocity is not more anomalous than that advected by the Gaussian random velocity. Whether the advecting velocity is non-Gaussian or Gaussian, similar scaling exponents of passive scalar are obtained with the same molecular diffusivity.展开更多
A new robust proportional-integral-derivative (PID) tracking control framework is considered for stochastic systems with non-Gaussian variable based on B-spline neural network approximation and T-S fuzzy model ident...A new robust proportional-integral-derivative (PID) tracking control framework is considered for stochastic systems with non-Gaussian variable based on B-spline neural network approximation and T-S fuzzy model identification. The tracked object is the statistical information of a given target probability density function (PDF), rather than a deterministic signal. Following B-spline approximation to the integrated performance function, the concerned problem is transferred into the tracking of given weights. Different from the previous related works, the time delay T-S fuzzy models with the exogenous disturbances are applied to identify the nonlinear weighting dynamics. Meanwhile, the generalized PID controller structure and the improved convex linear matrix inequalities (LMI) algorithms are proposed to fulfil the tracking problem. Furthermore, in order to enhance the robust performance, the peak-to-peak measure index is applied to optimize the tracking performance. Simulations are given to demonstrate the efficiency of the proposed approach.展开更多
A comparison between a non-Gaussian puff model and an advanced time-dependent model to simulate the pollutant dispersion in the Planetary Boundary Layer is presented. The puff model is based on a general technique for...A comparison between a non-Gaussian puff model and an advanced time-dependent model to simulate the pollutant dispersion in the Planetary Boundary Layer is presented. The puff model is based on a general technique for solving the K-equation, using the truncated Gram-Charlier expansion (type A) of the concentration field and finite set equations for the corresponding moments. The other model (named ADMM: Analytical Dispersion Multilayers Model) is an semi- analytical solution to the time-dependent two-dimensional advection-diffusion equation based on a discretization of the PBL in N sub-layers;in each sub-layers the advection-diffusion equation is solved by the Laplace transform technique, considering an average value for eddy diffusivity and the wind speed. A preliminary performance evaluation is shown in the case of continuous emission from an elevated source in a variable boundary layer. Both models were able to correctly reproduce the concentration field measured and so to be used as operative air pollution models.展开更多
The size of pores and throats is at the nano- meter scale in tight oil and shale gas zones, and the resistivity of these reservoirs is very high, so the reservoirs show more dielectric properties than conductivity pro...The size of pores and throats is at the nano- meter scale in tight oil and shale gas zones, and the resistivity of these reservoirs is very high, so the reservoirs show more dielectric properties than conductivity proper- ties. The conductive and dielectric characteristics of a parallel plate capacitor full of fresh water, NaCl solutions, and solid dielectrics, for example, sands are investigated in this paper, and the capacitance data of the non-gas capacitor are measured at different salinities and frequencies by a spectrum analyzer. The experimental results illustrate that the capacitance of this kind of capacitor is directly pro- portional to the salinity of the solutions and inversely proportional to the measuring frequency, the same as a vacuum parallel plate capacitor. The remarkable phenom- enon, however, is that the capacitance is inversely pro- portional to the square of the distance between two plates. The specific characteristic of this capacitor is different from the conventional parallel plate capacitor. In order to explain this phenomenon, the paper proposed a new concept, named "single micro ion capacitor", and established a novel model to describe the characteristics of this particular capacitor. Based on this new model, the theoretical capacitance value of the single micro ion capacitor is calculated, and its polarization and relaxation mechanisms are analyzed.展开更多
Wind field simulation in the surface layer is often used to manage natural resources in terms of air quality,gene flow(through pollen drift),and plant disease transmission(spore dispersion).Although Lagrangian stochas...Wind field simulation in the surface layer is often used to manage natural resources in terms of air quality,gene flow(through pollen drift),and plant disease transmission(spore dispersion).Although Lagrangian stochastic(LS)models describe stochastic wind behaviors,such models assume that wind velocities follow Gaussian distributions.However,measured surface-layer wind velocities show a strong skewness and kurtosis.This paper presents an improved model,a non-Gaussian LS model,which incorporates controllable non-Gaussian random variables to simulate the targeted non-Gaussian velocity distribution with more accurate skewness and kurtosis.Wind velocity statistics generated by the non-Gaussian model are evaluated by using the field data from the Cooperative Atmospheric Surface Exchange Study,October 1999 experimental dataset and comparing the data with statistics from the original Gaussian model.Results show that the non-Gaussian model improves the wind trajectory simulation by stably producing precise skewness and kurtosis in simulated wind velocities without sacrificing other features of the traditional Gaussian LS model,such as the accuracy in the mean and variance of simulated velocities.This improvement also leads to better accuracy in friction velocity(i.e.,a coupling of three-dimensional velocities).The model can also accommodate various non-Gaussian wind fields and a wide range of skewness–kurtosis combinations.Moreover,improved skewness and kurtosis in the simulated velocity will result in a significantly different dispersion for wind/particle simulations.Thus,the non-Gaussian model is worth applying to wind field simulation in the surface layer.展开更多
A new on-line predictive monitoring and prediction model for periodic biological processes is proposed using the multiway non-Gaussian modeling. The basic idea of this approach is to use multiway non-Gaussian modeling...A new on-line predictive monitoring and prediction model for periodic biological processes is proposed using the multiway non-Gaussian modeling. The basic idea of this approach is to use multiway non-Gaussian modeling to extract some dominant key components from daily normal operation data in a periodic process, and subsequently combining these components with predictive statistical process monitoring techniques. The proposed predictive monitoring method has been applied to fault detection and diagnosis in the biological wastewater-treatment process, which is based on strong diurnal characteristics. The results show the power and advantages of the proposed predictive monitoring of a continuous process using the multiway predictive monitoring concept, which is thus able to give very useful conceptual results for a daily monitoring process and also enables a more rapid detection of the process fault than other traditional monitoring methods.展开更多
Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,...Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.展开更多
Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Ar...Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).展开更多
基金support provided by the National Natural Science Foundation of China(22122802,22278044,and 21878028)the Chongqing Science Fund for Distinguished Young Scholars(CSTB2022NSCQ-JQX0021)the Fundamental Research Funds for the Central Universities(2022CDJXY-003).
文摘To equip data-driven dynamic chemical process models with strong interpretability,we develop a light attention–convolution–gate recurrent unit(LACG)architecture with three sub-modules—a basic module,a brand-new light attention module,and a residue module—that are specially designed to learn the general dynamic behavior,transient disturbances,and other input factors of chemical processes,respectively.Combined with a hyperparameter optimization framework,Optuna,the effectiveness of the proposed LACG is tested by distributed control system data-driven modeling experiments on the discharge flowrate of an actual deethanization process.The LACG model provides significant advantages in prediction accuracy and model generalization compared with other models,including the feedforward neural network,convolution neural network,long short-term memory(LSTM),and attention-LSTM.Moreover,compared with the simulation results of a deethanization model built using Aspen Plus Dynamics V12.1,the LACG parameters are demonstrated to be interpretable,and more details on the variable interactions can be observed from the model parameters in comparison with the traditional interpretable model attention-LSTM.This contribution enriches interpretable machine learning knowledge and provides a reliable method with high accuracy for actual chemical process modeling,paving a route to intelligent manufacturing.
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supported by the National Defense Advanced Research Foundation of China (51407020304DZ0223).
文摘To validate the potential space-time adaptive processing (STAP) algorithms for airborne bistatic radar clutter suppression under nonstationary and non-Gaussian clutter environments, a statistically non-Gaussian, space-time clutter model in varying bistatic geometrical scenarios is presented. The inclusive effects of the model contain the range dependency of bistatic clutter spectrum and clutter power variation in range-angle cells. To capture them, a new approach to coordinate system conversion is initiated into formulating bistatic geometrical model, and the bistatic non-Gaussian amplitude clutter representation method based on a compound model is introduced. The veracity of the geometrical model is validated by using the bistatic configuration parameters of multi-channel airborne radar measurement (MCARM) experiment. And simulation results manifest that the proposed model can accurately shape the space-time clutter spectrum tied up with specific airborne bistatic radar scenario and can characterize the heterogeneity of clutter amplitude distribution in practical clutter environments.
基金Project supported by the Major Program of the National Natural Science Foundation (Grant No 10335010) and the National Natural Science Foundation-the Science Foundation of China Academy of Engineering Physics NSAF (Grant No 10576005).Acknowledgement We are grateful to Professor She Zhen-Su for useful suggestions and Dr Sun Peng and Dr Zhang Xiao- Qiang for extensive discussion.
文摘In this paper, we have introduced a shell-model of Kraichnan's passive scalar problem. Different from the original problem, the prescribed random velocity field is non-Gaussian and σ correlated in time, and its introduction is inspired by She and Levveque (Phys. Rev. Lett. 72, 336 (1994)). For comparison, we also give the passive scalar advected by the Gaussian random velocity field. The anomalous scaling exponents H(p) of passive scalar advected by these two kinds of random velocities above are determined for structure function with values of p up to 15 by Monte Carlo simulations of the random shell model, with Gear methods used to solve the stochastic differential equations. We find that the H(p) advected by the non-Gaussian random velocity is not more anomalous than that advected by the Gaussian random velocity. Whether the advecting velocity is non-Gaussian or Gaussian, similar scaling exponents of passive scalar are obtained with the same molecular diffusivity.
基金supported by National Natural Science Foundationof China (No. 60472065, No. 60774013).
文摘A new robust proportional-integral-derivative (PID) tracking control framework is considered for stochastic systems with non-Gaussian variable based on B-spline neural network approximation and T-S fuzzy model identification. The tracked object is the statistical information of a given target probability density function (PDF), rather than a deterministic signal. Following B-spline approximation to the integrated performance function, the concerned problem is transferred into the tracking of given weights. Different from the previous related works, the time delay T-S fuzzy models with the exogenous disturbances are applied to identify the nonlinear weighting dynamics. Meanwhile, the generalized PID controller structure and the improved convex linear matrix inequalities (LMI) algorithms are proposed to fulfil the tracking problem. Furthermore, in order to enhance the robust performance, the peak-to-peak measure index is applied to optimize the tracking performance. Simulations are given to demonstrate the efficiency of the proposed approach.
文摘A comparison between a non-Gaussian puff model and an advanced time-dependent model to simulate the pollutant dispersion in the Planetary Boundary Layer is presented. The puff model is based on a general technique for solving the K-equation, using the truncated Gram-Charlier expansion (type A) of the concentration field and finite set equations for the corresponding moments. The other model (named ADMM: Analytical Dispersion Multilayers Model) is an semi- analytical solution to the time-dependent two-dimensional advection-diffusion equation based on a discretization of the PBL in N sub-layers;in each sub-layers the advection-diffusion equation is solved by the Laplace transform technique, considering an average value for eddy diffusivity and the wind speed. A preliminary performance evaluation is shown in the case of continuous emission from an elevated source in a variable boundary layer. Both models were able to correctly reproduce the concentration field measured and so to be used as operative air pollution models.
基金Basic Science Program of Advanced Well Logging Technology of CNPC (2014A-2319)the Science and Technology Program (G12-3) of State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation of SWPU (Southwest Petroleum University)
文摘The size of pores and throats is at the nano- meter scale in tight oil and shale gas zones, and the resistivity of these reservoirs is very high, so the reservoirs show more dielectric properties than conductivity proper- ties. The conductive and dielectric characteristics of a parallel plate capacitor full of fresh water, NaCl solutions, and solid dielectrics, for example, sands are investigated in this paper, and the capacitance data of the non-gas capacitor are measured at different salinities and frequencies by a spectrum analyzer. The experimental results illustrate that the capacitance of this kind of capacitor is directly pro- portional to the salinity of the solutions and inversely proportional to the measuring frequency, the same as a vacuum parallel plate capacitor. The remarkable phenom- enon, however, is that the capacitance is inversely pro- portional to the square of the distance between two plates. The specific characteristic of this capacitor is different from the conventional parallel plate capacitor. In order to explain this phenomenon, the paper proposed a new concept, named "single micro ion capacitor", and established a novel model to describe the characteristics of this particular capacitor. Based on this new model, the theoretical capacitance value of the single micro ion capacitor is calculated, and its polarization and relaxation mechanisms are analyzed.
基金financial support for this research from a USDA-AFRI Foundational Grant (Grant No. 2012-67013-19687)from the Illinois State Water Survey at the University of Illinois at Urbana—Champaign
文摘Wind field simulation in the surface layer is often used to manage natural resources in terms of air quality,gene flow(through pollen drift),and plant disease transmission(spore dispersion).Although Lagrangian stochastic(LS)models describe stochastic wind behaviors,such models assume that wind velocities follow Gaussian distributions.However,measured surface-layer wind velocities show a strong skewness and kurtosis.This paper presents an improved model,a non-Gaussian LS model,which incorporates controllable non-Gaussian random variables to simulate the targeted non-Gaussian velocity distribution with more accurate skewness and kurtosis.Wind velocity statistics generated by the non-Gaussian model are evaluated by using the field data from the Cooperative Atmospheric Surface Exchange Study,October 1999 experimental dataset and comparing the data with statistics from the original Gaussian model.Results show that the non-Gaussian model improves the wind trajectory simulation by stably producing precise skewness and kurtosis in simulated wind velocities without sacrificing other features of the traditional Gaussian LS model,such as the accuracy in the mean and variance of simulated velocities.This improvement also leads to better accuracy in friction velocity(i.e.,a coupling of three-dimensional velocities).The model can also accommodate various non-Gaussian wind fields and a wide range of skewness–kurtosis combinations.Moreover,improved skewness and kurtosis in the simulated velocity will result in a significantly different dispersion for wind/particle simulations.Thus,the non-Gaussian model is worth applying to wind field simulation in the surface layer.
基金the Korea Research Foundation Grant Funded by the Korean Government (MOEHRD) (KRF-2007-331-D00089) Funded by Seoul Development Institute (CS070160)
文摘A new on-line predictive monitoring and prediction model for periodic biological processes is proposed using the multiway non-Gaussian modeling. The basic idea of this approach is to use multiway non-Gaussian modeling to extract some dominant key components from daily normal operation data in a periodic process, and subsequently combining these components with predictive statistical process monitoring techniques. The proposed predictive monitoring method has been applied to fault detection and diagnosis in the biological wastewater-treatment process, which is based on strong diurnal characteristics. The results show the power and advantages of the proposed predictive monitoring of a continuous process using the multiway predictive monitoring concept, which is thus able to give very useful conceptual results for a daily monitoring process and also enables a more rapid detection of the process fault than other traditional monitoring methods.
基金funded by the National Natural Science Foundation of China(Grant Nos.U22A20166 and 12172230)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515012654)+1 种基金funded by the National Natural Science Foundation of China(Grant Nos.U22A20166 and 12172230)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515012654)。
文摘Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.
基金supported by the Chinese–Norwegian Collaboration Projects within Climate Systems jointly funded by the National Key Research and Development Program of China (Grant No.2022YFE0106800)the Research Council of Norway funded project,MAPARC (Grant No.328943)+2 种基金the support from the Research Council of Norway funded project,COMBINED (Grant No.328935)the National Natural Science Foundation of China (Grant No.42075030)the Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX23_1314)。
文摘Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).