A tablet consisting of direct-acting antiviral agents,ledipasvir（a NS5 A protein inhibitor） and sofosbuvir（a NS5 B polymerase inhibitor）,is the first fixed-dose preparation used in the antiviral therapy of hepatit...A tablet consisting of direct-acting antiviral agents,ledipasvir（a NS5 A protein inhibitor） and sofosbuvir（a NS5 B polymerase inhibitor）,is the first fixed-dose preparation used in the antiviral therapy of hepatitis C.A model-based meta-analysis of ledipasvir and GS331007,the primary metabolite of sofosbuvir,enabled the integration of pharmacokinetic（PK） information from separate clinical trials and the quantitative characterization of the population pharmacokinetics of these two drugs.A systematic publication search was conducted for the clinical studies of ledipasvir and sofosbuvir.A total of 401 arm-level aggregate concentrations of GS331007 and 188 concentrations of ledipasvir were used for PK modeling.A two-compartment disposition model was used for both ledipasvir and GS331007.Zero-order absorption was applied for ledipasvir PK modeling,and a combined zero- and first-order absorption was used for the modeling of GS331007.Absorption lag was observed in concentration-time profiles of both ledipasvir and GS331007.To aid the development of direct-acting antiviral drugs,our established PK models provided a basis for the further PK-viral kinetic studies of ledipasvir and sofosbuvir.展开更多
Robustness testing for safety-critical embedded software is still a challenge in its nascent stages. In this paper, we propose a practical methodology and implement an environment by employing model-based robustness t...Robustness testing for safety-critical embedded software is still a challenge in its nascent stages. In this paper, we propose a practical methodology and implement an environment by employing model-based robustness testing for embedded software systems. It is a system-level black-box testing approach in which the fault behaviors of embedded software is triggered with the aid of modelbased fault injection by the support of an executable model-driven hardware-in-loop （HIL） testing environment. The prototype implementation of the robustness testing environment based on the proposed approach is experimentally discussed and illustrated by industrial case studies based on several avionics-embedded software systems. The results show that our proposed and implemented robustness testing method and environment are effective to find more bugs, and reduce burdens of testing engineers to enhance efficiency of testing tasks, especially for testing complex embedded systems.展开更多
This paper proposes a model-based prognostics method that couples the Extended Kalman Filter(EKF) and a new developed linearization method. The proposed prognostics method is developed in the context of fatigue crack ...This paper proposes a model-based prognostics method that couples the Extended Kalman Filter(EKF) and a new developed linearization method. The proposed prognostics method is developed in the context of fatigue crack propagation in fuselage panels where the model parameters are unknown and the crack propagation is affected by different types of uncertainties. The coupled method is composed of two steps. The first step employs EKF to estimate the unknown model parameters and the current damage state. In the second step, the proposed efficient linearization method is applied to compute analytically the statistical distribution of the damage evolution path in some future time. A numerical case study is implemented to evaluate the performance of the proposed method. The results show that the coupled EKF-linearization method provides satisfactory results: the EKF algorithm well identifies the model parameters, and the linearization method gives comparable prediction results to Monte Carlo(MC) method while leading to very significant computational cost saving. The proposed prognostics method for fatigue crack growth can be used for developing predictive maintenance strategy for an aircraft fleet, in which case, the computational cost saving is significantly meaningful.展开更多
Numerous clustering algorithms are valuable in pattern recognition in forest vegetation,with new ones continually being proposed.While some are well-known,others are underutilized in vegetation science.This study comp...Numerous clustering algorithms are valuable in pattern recognition in forest vegetation,with new ones continually being proposed.While some are well-known,others are underutilized in vegetation science.This study compares the performance of practical iterative reallocation algorithms with model-based clustering algorithms.The data is from forest vegetation in Virginia(United States),the Hyrcanian Forest(Asia),and European beech forests.Practical iterative reallocation algorithms were applied as non-hierarchical methods and Finite Gaussian mixture modeling was used as a model-based clustering method.Due to limitations on dimensionality in model-based clustering,principal coordinates analysis was employed to reduce the dataset’s dimensions.A log transformation was applied to achieve a normal distribution for the pseudo-species data before calculating the Bray-Curtis dissimilarity.The findings indicate that the reallocation of misclassified objects based on silhouette width(OPTSIL)with Flexible-β(-0.25)had the highest mean among the tested clustering algorithms with Silhouette width 1(REMOS1)with Flexible-β(-0.25)second.However,model-based clustering performed poorly.Based on these results,it is recommended using OPTSIL with Flexible-β(-0.25)and REMOS1 with Flexible-β(-0.25)for forest vegetation classification instead of model-based clustering particularly for heterogeneous datasets common in forest vegetation community data.展开更多
Unlike traditional propeller-driven underwater vehicles,blended-wing-body underwater gliders(BWBUGs)achieve zigzag gliding through periodic adjustments of their net buoyancy,enhancing their cruising capabilities while...Unlike traditional propeller-driven underwater vehicles,blended-wing-body underwater gliders(BWBUGs)achieve zigzag gliding through periodic adjustments of their net buoyancy,enhancing their cruising capabilities while mini-mizing energy consumption.However,enhancing gliding performance is challenging due to the complex system design and limited design experience.To address this challenge,this paper introduces a model-based,multidisciplinary system design optimization method for BWBUGs at the conceptual design stage.First,a model-based,multidisciplinary co-simulation design framework is established to evaluate both system-level and disciplinary indices of BWBUG performance.A data-driven,many-objective multidisciplinary optimization is subsequently employed to explore the design space,yielding 32 Pareto optimal solutions.Finally,a model-based physical system simulation,which represents the design with the largest hyper-volume contribution among the 32 final designs,is established.Its gliding perfor-mance,validated by component behavior,lays the groundwork for constructing the entire system’s digital prototype.In conclusion,this model-based,multidisciplinary design optimization method effectively generates design schemes for innovative underwater vehicles,facilitating the development of digital prototypes.展开更多
This paper studies the problem of designing a modelbased decentralized dynamic periodic event-triggering mechanism(DDPETM)for networked control systems(NCSs)subject to packet losses and external disturbances.Firstly,t...This paper studies the problem of designing a modelbased decentralized dynamic periodic event-triggering mechanism(DDPETM)for networked control systems(NCSs)subject to packet losses and external disturbances.Firstly,the entire NCSs,comprising the triggering mechanism,packet losses and output-based controller,are unified into a hybrid dynamical framework.Secondly,by introducing dynamic triggering variables,the DDPETM is designed to conserve network resources while guaranteeing desired performance properties and tolerating the maximum allowable number of successive packet losses.Thirdly,some stability conditions are derived using the Lyapunov approach.Differing from the zero-order-hold(ZOH)case,the model-based control sufficiently exploits the model information at the controller side.Between two updates,the controller predicts the plant state based on the models and received feedback information.With the model-based control,less transmission may be expected than with ZOH.Finally,numerical examples and comparative experiments demonstrate the effectiveness of the proposed method.展开更多
Individualized models of respiratory mechanics help to reduce potential harmful effects of mechanical ventilation by supporting the evaluation of patient-specific lung protective ventilation strategies. Assessing vent...Individualized models of respiratory mechanics help to reduce potential harmful effects of mechanical ventilation by supporting the evaluation of patient-specific lung protective ventilation strategies. Assessing ventilation inhomogeneities might be an important aspect in optimizing ventilator settings. The aim of this studyis to capture and analyze ventilation inhomogeneity by a mathematical model using clinical data. The results show that the lung physiology of mechanically ventilated patients without lung condition can be described by an inhomogeneity model revealing two alveolar compartments with median time constants of 0.4 and 3.9 s. Thus, the IHM in combination with specific ventilation maneuver might be suitable to capture lung physiology for model-based optimization of ventilator settings but requires additional image-based investigations to further support the validity of the model.展开更多
基金Janssen Research & DevelopmentChina，Pfizer Scholarship for Pharmacometrics during this project
文摘A tablet consisting of direct-acting antiviral agents,ledipasvir（a NS5 A protein inhibitor） and sofosbuvir（a NS5 B polymerase inhibitor）,is the first fixed-dose preparation used in the antiviral therapy of hepatitis C.A model-based meta-analysis of ledipasvir and GS331007,the primary metabolite of sofosbuvir,enabled the integration of pharmacokinetic（PK） information from separate clinical trials and the quantitative characterization of the population pharmacokinetics of these two drugs.A systematic publication search was conducted for the clinical studies of ledipasvir and sofosbuvir.A total of 401 arm-level aggregate concentrations of GS331007 and 188 concentrations of ledipasvir were used for PK modeling.A two-compartment disposition model was used for both ledipasvir and GS331007.Zero-order absorption was applied for ledipasvir PK modeling,and a combined zero- and first-order absorption was used for the modeling of GS331007.Absorption lag was observed in concentration-time profiles of both ledipasvir and GS331007.To aid the development of direct-acting antiviral drugs,our established PK models provided a basis for the further PK-viral kinetic studies of ledipasvir and sofosbuvir.
基金the Aeronautics Science Foundation of China(No.2011ZD51055)Science and Technology on Reliability&Environmental Engineering Laboratory(No.302367)the National Pre-Research Foundation of China(No.51319080201)
文摘Robustness testing for safety-critical embedded software is still a challenge in its nascent stages. In this paper, we propose a practical methodology and implement an environment by employing model-based robustness testing for embedded software systems. It is a system-level black-box testing approach in which the fault behaviors of embedded software is triggered with the aid of modelbased fault injection by the support of an executable model-driven hardware-in-loop （HIL） testing environment. The prototype implementation of the robustness testing environment based on the proposed approach is experimentally discussed and illustrated by industrial case studies based on several avionics-embedded software systems. The results show that our proposed and implemented robustness testing method and environment are effective to find more bugs, and reduce burdens of testing engineers to enhance efficiency of testing tasks, especially for testing complex embedded systems.
基金partially funded by the National Natural Science Foundation of China (No.51805262)
文摘This paper proposes a model-based prognostics method that couples the Extended Kalman Filter(EKF) and a new developed linearization method. The proposed prognostics method is developed in the context of fatigue crack propagation in fuselage panels where the model parameters are unknown and the crack propagation is affected by different types of uncertainties. The coupled method is composed of two steps. The first step employs EKF to estimate the unknown model parameters and the current damage state. In the second step, the proposed efficient linearization method is applied to compute analytically the statistical distribution of the damage evolution path in some future time. A numerical case study is implemented to evaluate the performance of the proposed method. The results show that the coupled EKF-linearization method provides satisfactory results: the EKF algorithm well identifies the model parameters, and the linearization method gives comparable prediction results to Monte Carlo(MC) method while leading to very significant computational cost saving. The proposed prognostics method for fatigue crack growth can be used for developing predictive maintenance strategy for an aircraft fleet, in which case, the computational cost saving is significantly meaningful.
基金financially supported by the vice chancellor for research and technology of Urmia University
文摘Numerous clustering algorithms are valuable in pattern recognition in forest vegetation,with new ones continually being proposed.While some are well-known,others are underutilized in vegetation science.This study compares the performance of practical iterative reallocation algorithms with model-based clustering algorithms.The data is from forest vegetation in Virginia(United States),the Hyrcanian Forest(Asia),and European beech forests.Practical iterative reallocation algorithms were applied as non-hierarchical methods and Finite Gaussian mixture modeling was used as a model-based clustering method.Due to limitations on dimensionality in model-based clustering,principal coordinates analysis was employed to reduce the dataset’s dimensions.A log transformation was applied to achieve a normal distribution for the pseudo-species data before calculating the Bray-Curtis dissimilarity.The findings indicate that the reallocation of misclassified objects based on silhouette width(OPTSIL)with Flexible-β(-0.25)had the highest mean among the tested clustering algorithms with Silhouette width 1(REMOS1)with Flexible-β(-0.25)second.However,model-based clustering performed poorly.Based on these results,it is recommended using OPTSIL with Flexible-β(-0.25)and REMOS1 with Flexible-β(-0.25)for forest vegetation classification instead of model-based clustering particularly for heterogeneous datasets common in forest vegetation community data.
基金supported by the Postdoctoral Fellowship Program of CPSF(Grant No.GZC20242194)the National Natural Science Foundation of China(Grant Nos.52175251 and 52205268)+1 种基金the Industry Key Technology Research Fund Project of Northwestern Polytechnical University(Grant No.HYGJXM202318)the National Basic Scientific Research Program(Grant No.JCKY2021206B005).
文摘Unlike traditional propeller-driven underwater vehicles,blended-wing-body underwater gliders(BWBUGs)achieve zigzag gliding through periodic adjustments of their net buoyancy,enhancing their cruising capabilities while mini-mizing energy consumption.However,enhancing gliding performance is challenging due to the complex system design and limited design experience.To address this challenge,this paper introduces a model-based,multidisciplinary system design optimization method for BWBUGs at the conceptual design stage.First,a model-based,multidisciplinary co-simulation design framework is established to evaluate both system-level and disciplinary indices of BWBUG performance.A data-driven,many-objective multidisciplinary optimization is subsequently employed to explore the design space,yielding 32 Pareto optimal solutions.Finally,a model-based physical system simulation,which represents the design with the largest hyper-volume contribution among the 32 final designs,is established.Its gliding perfor-mance,validated by component behavior,lays the groundwork for constructing the entire system’s digital prototype.In conclusion,this model-based,multidisciplinary design optimization method effectively generates design schemes for innovative underwater vehicles,facilitating the development of digital prototypes.
基金supported by the National Natural Science Foundation of China(U21A20477,61722302,61573069,61903290)the Fundamental Research Funds for the Central Universities(DUT19ZD218).
文摘This paper studies the problem of designing a modelbased decentralized dynamic periodic event-triggering mechanism(DDPETM)for networked control systems(NCSs)subject to packet losses and external disturbances.Firstly,the entire NCSs,comprising the triggering mechanism,packet losses and output-based controller,are unified into a hybrid dynamical framework.Secondly,by introducing dynamic triggering variables,the DDPETM is designed to conserve network resources while guaranteeing desired performance properties and tolerating the maximum allowable number of successive packet losses.Thirdly,some stability conditions are derived using the Lyapunov approach.Differing from the zero-order-hold(ZOH)case,the model-based control sufficiently exploits the model information at the controller side.Between two updates,the controller predicts the plant state based on the models and received feedback information.With the model-based control,less transmission may be expected than with ZOH.Finally,numerical examples and comparative experiments demonstrate the effectiveness of the proposed method.
基金The German Federal Ministry of Education and Research (WiM-Vent, Grants01IB10002D, PulMODS Grant 01DR12095) EU FP7 PIRSES--GA-2012-318943 eTime
文摘Individualized models of respiratory mechanics help to reduce potential harmful effects of mechanical ventilation by supporting the evaluation of patient-specific lung protective ventilation strategies. Assessing ventilation inhomogeneities might be an important aspect in optimizing ventilator settings. The aim of this studyis to capture and analyze ventilation inhomogeneity by a mathematical model using clinical data. The results show that the lung physiology of mechanically ventilated patients without lung condition can be described by an inhomogeneity model revealing two alveolar compartments with median time constants of 0.4 and 3.9 s. Thus, the IHM in combination with specific ventilation maneuver might be suitable to capture lung physiology for model-based optimization of ventilator settings but requires additional image-based investigations to further support the validity of the model.
