The structural dynamic response reconstruction technology can extract unmeasured information from limited measured data,significantly impacting vibration control,load identification,parameter identification,fault diag...The structural dynamic response reconstruction technology can extract unmeasured information from limited measured data,significantly impacting vibration control,load identification,parameter identification,fault diagnosis,and related fields.This paper proposes a dynamic response reconstruction method based on the Kalman filter,which simultaneously identifies external excitation and reconstructs dynamic responses at unmeasured positions.The weighted least squares method determines the load weighting matrix for excitation identification,while the minimum variance unbiased estimation determines the Kalman filter gain.The excitation prediction Kalman filter is constructed through time,excitation,and measurement updates.Subsequently,the response at the target point is reconstructed using the state vector,observation matrix,and excitation influence matrix obtained through the excitation prediction Kalman filter algorithm.An algorithm for reconstructing responses in continuous system using the excitation prediction Kalman filtering algorithm in modal space is derived.The proposed structural dynamic response reconstruction method evaluates the response reconstruction and the load identification performance under various load types and errors through simulation examples.Results demonstrate the accurate excitation identification under different load conditions and simultaneous reconstruction of target point responses,verifying the feasibility and reliability of the proposed method.展开更多
In this paper,a linear/nonlinear switching active disturbance rejection control(SADRC)based decoupling control approach is proposed to deal with some difficult control problems in a class of multi-input multi-output(M...In this paper,a linear/nonlinear switching active disturbance rejection control(SADRC)based decoupling control approach is proposed to deal with some difficult control problems in a class of multi-input multi-output(MIMO)systems such as multi-variables,disturbances,and coupling,etc.Firstly,the structure and parameter tuning method of SADRC is introduced into this paper.Followed on this,virtual control variables are adopted into the MIMO systems,making the systems decoupled.Then the SADRC controller is designed for every subsystem.After this,a stability analyzed method via the Lyapunov function is proposed for the whole system.Finally,some simulations are presented to demonstrate the anti-disturbance and robustness of SADRC,and results show SADRC has a potential applications in engineering practice.展开更多
The functions of bounded φ-variation are development and generalization of bounded variation functions in the usual sense.Henstock-Kurzweil integral is a very useful tool for some discontinuous systems. In this paper...The functions of bounded φ-variation are development and generalization of bounded variation functions in the usual sense.Henstock-Kurzweil integral is a very useful tool for some discontinuous systems. In this paper, by using Henstock-Kurzweil integral, we establish theorems of continuous dependence of bounded D-variation solutions on parameter for a class of discontinuous systems on the base of D-function. These results are essential generalizations of continuous dependence of bounded variation solutions on parameter for the systems.展开更多
An example is presented to introduce the concept of implicit continuity proposed as contrasted with the explicit continuity.A sufficient and necessary condition of the implicit continuity is given and proved in forms ...An example is presented to introduce the concept of implicit continuity proposed as contrasted with the explicit continuity.A sufficient and necessary condition of the implicit continuity is given and proved in forms of implicit system.This condition also offers the solution of initial values at the points where the dynamic system is discontinuous.Some discussions are contributed to the physical significance of implicit continuity.展开更多
Continuous System Simulation (CSS) is a powerful way to study the behaviour of differential-algebraic equation models. Differential-algebraic equation modelling goes back to Newton and works well for models of e.g. ph...Continuous System Simulation (CSS) is a powerful way to study the behaviour of differential-algebraic equation models. Differential-algebraic equation modelling goes back to Newton and works well for models of e.g. physical systems where stochasticity plays almost no role, and where only a single attribute of an object is studied over time. However, when results from a deterministic CSS model are compared with results from a Discrete Event Simulation (DES) model, they are often inconsistent. The reasons behind this CSS-DES inconsistency are nowadays well understood. In this paper, we demonstrate that a CSS model can contain both continuous state variables (compartments) that change continuously over time and discrete state variables (also compartments) that model discrete entities and change by integer amounts. In both cases, the time-slicing method is used to advance time. Furthermore, stochasticity can and should play the same role in CSS as it does in DES. This paper first explains how a well-defined conceptual model can be stepwise transformed in a consistent way into a CSS model. These transformation steps provide insights into how to construct a consistent CSS model. In short, this is about preserving uncertainties, attributes and dynamic properties. An additional benefit of this approach is that continuous and discrete sub-models can interact within the same model, without having to combine different types of simulation languages, types of time handling and incongruent concepts. To facilitate the use and understanding of stochastic CSS, this paper is also intended to serve as a guide to performing consistent CSS modelling and simulation. Furthermore, an open source tool for collecting and analyzing the outputs from a stochastic CSS model and analyzing and presenting the results in statistical form is also developed and made available to the reader.展开更多
Dear Editor,This letter proposes a reinforcement learning-based predictive learning algorithm for unknown continuous-time nonlinear systems with observation loss.Firstly,we construct a temporal nonzero-sum game over p...Dear Editor,This letter proposes a reinforcement learning-based predictive learning algorithm for unknown continuous-time nonlinear systems with observation loss.Firstly,we construct a temporal nonzero-sum game over predictive control input sequences,deriving multiple optimal predictive control input sequences from its solution.展开更多
Pediatric type 1 diabetes(T1D)is a lifelong condition requiring meticulous glucose management to prevent acute and chronic complications.Conventional management of diabetic patients does not allow for continuous monit...Pediatric type 1 diabetes(T1D)is a lifelong condition requiring meticulous glucose management to prevent acute and chronic complications.Conventional management of diabetic patients does not allow for continuous monitoring of glucose trends,and can place patients at risk for hypo-and hyperglycemia.Continuous glucose monitors(CGMs)have emerged as a mainstay for pediatric diabetic care and are continuing to advance treatment by providing real-time blood glucose(BG)data,with trend analysis aided by machine learning(ML)algorithms.These predictive analytics serve to prevent against dangerous BG variations in the perioperative environment for fasted children undergoing surgical stress.Integration of CGM data into electronic health records(EHR)is essential,as it establishes a foundation for future technologic interfaces with artificial intelligence(AI).Challenges in perioperative CGM implementation include equitable device access,protection of patient privacy and data accuracy,ensuring institution of standardized protocols,and financing the cumbersome healthcare costs associated with staff training and technology platforms.This paper advocates for implementation of CGM data into the EHR utilizing multiple facets of AI/ML algorithms.展开更多
Crops produced using the practice of continuous cropping can become seriously damaged by plant-parasitic nematodes,an important indicator of continuous cropping obstacles.As a typical and important perennial economic ...Crops produced using the practice of continuous cropping can become seriously damaged by plant-parasitic nematodes,an important indicator of continuous cropping obstacles.As a typical and important perennial economic crop,dragon fruit is prone to serious plant-parasitic nematode infestation;however,whether it encounters continuous cropping obstacles remains unclear.Here,we studied plant-parasitic nematodes(Meloidogyne spp.and Tylenchorhynchus sp.)in the soil and roots,soil nematode communities,metabolic footprint,soil integrated fertility,and the yield of intensively planted dragon fruit under non-continuous cropping(Y1)and 3 years(Y3)and 5 years(Y5)of continuous cropping,to determine potential continuous-cropping obstacles and factors that affect the yield of this fruit.The largest numbers of plant-parasitic nematodes in the soil and roots were observed in Y5;the associated yield was reduced,and the dragon fruit was severely stressed.Further analysis of the composition,diversity,and ecological function indices of soil nematodes showed that the soil ecological environment deteriorated after 3 years of continuous cropping,with Y5 having the worst results.Similarly,the soil at Y5 had a significant inhibitory effect on the growth and reproduction of Caenorhabditis elegans.Mantel test analysis and a random forest model showed that soil available phosphorus,soil exchange calcium,and soil nematode abundance and diversity were related significantly to yield.Partial least squares path modeling revealed that soil fertility and soil nematode diversity directly impacts the yield of continuously cropped dragon fruit.In summary,continuous cropping obstacles occurred in Y5 of intensive dragon fruit cultivation,with soil nematode diversity and soil fertility determining the crop's yield.展开更多
To address the current issues with the conventional slide gate system utilized in the steel teeming process,a unique electromagnetic induction controlled automated steel teeming(EICAST)technology has been developed.Co...To address the current issues with the conventional slide gate system utilized in the steel teeming process,a unique electromagnetic induction controlled automated steel teeming(EICAST)technology has been developed.Cooling means of spiral coil in this technology is directly related to its service life.Firstly,heat transfer processes of air cooling and spray cooling were compared and analyzed.Secondly,the impacts of water temperature,water flow rate and air flow rate were examined in order to maximize the spray cooling effect.To maintain coil temperature at a low value consistently throughout the entire thermal cycle process of the ladle,a combined cooling mode was finally employed.Numerical simulation was applied to examine the coil temperature variation with different cooling systems and characteristics.Before coil operation,spray cooling is said to be more effective.By controlling the water flow rate and air flow rate,the spray cooling effect is enhanced.However,water temperature has little or no impact when using spray cooling.Air cooling during the secondary refining process and spray cooling prior to coil operation are combined to further lower coil temperature.When the direction of the spray cooling is from bottom to top,the coil temperature is lowered below 165℃.A practical induction coil cooling plan was provided for the EICAST technology’s production process.展开更多
To handle input and output time delays that commonly exist in many networked control systems(NCSs), a new robust continuous sliding mode control(CSMC) scheme is proposed for the output tracking in uncertain single inp...To handle input and output time delays that commonly exist in many networked control systems(NCSs), a new robust continuous sliding mode control(CSMC) scheme is proposed for the output tracking in uncertain single input-single-output(SISO) networked control systems. This scheme consists of three consecutive steps. First, although the network-induced delay in those systems can be effectively handled by using Pade approximation(PA), the unmatched disturbance cames out as another difficulty in the control design. Second, to actively estimate this unmatched disturbance, a generalized proportional integral observer(GPIO) technique is utilized based on only one measured state. Third, by constructing a new sliding manifold with the aid of the estimated unmatched disturbance and states, a GPIO-based CSMC is synthesized, which is employed to cope with not only matched and unmatched disturbances, but also networkinduced delays. The stability of the entire closed-loop system under the proposed GPIO-based CSMC is detailedly analyzed.The promising tracking efficiency and feasibility of the proposed control methodology are verified through simulations and experiments on Quanser's servo module for motion control under various test conditions.展开更多
1.Introduction.Pancreaticoduodenectomy is an essential surgical procedure for the treatment of malignant tumors in the pancreatic head,distal common bile duct,and duodenal papilla,and is widely used in clinical practi...1.Introduction.Pancreaticoduodenectomy is an essential surgical procedure for the treatment of malignant tumors in the pancreatic head,distal common bile duct,and duodenal papilla,and is widely used in clinical practice.One of the primary determinants of surgical success is the durability of the pancreaticojejunal anastomosis.展开更多
Background:Continuous care for children with enterostomy and their families has been gaining popularity in China.Objective:To evaluate the feasibility of continuous care for children with enterostomy and their familie...Background:Continuous care for children with enterostomy and their families has been gaining popularity in China.Objective:To evaluate the feasibility of continuous care for children with enterostomy and their families in China.Methods:The PubMed,Web of Science,Embase,Cochrane Library,EBSCO,CNKI,CBM,VIP,and WanFang were searched for clinical trials until December 30,2025.Two reviewers independently searched articles,evaluated quality and extracted data.This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA).Results:33 studies involving 2774 participants were included.The meta-analysis showed that continuous care strategy can significantly reduce the incidence of complications in children with enterostomy(OR=0.20,95%CI=0.16-0.26,p<0.001,I2=0%),effectively improve the family caregiver ability for enterostomy(MD=-10.34,95%CI=-13.82 to-6.85,p<0.001,I2=99%),shorten the time for family members to replace stoma bags(MD=-13.57,95%CI=-19.66 to-7.49,p<0.001,I2=100%),and alleviate negative emotions such as anxiety(SMD=-1.80,95%CI=-2.36 to-1.23,p<0.001,I2=92%)and depression(SMD=-1.54,95%CI=-2.04 to-1.04,p<0.001,I2=89%)in the families of the affected children.Conclusions:Continuous care can reduce complications of enterostomy in children,improve the family caregiver ability for enterostomy and alleviate negative emotions of family members such as anxiety and depression.展开更多
The transient phenomena of re-oxidation and slag entrapment occurring in the tundish during the ladle change-over process have been proven detrimental to clean steel production.Therefore,an unsteady three-phase turbul...The transient phenomena of re-oxidation and slag entrapment occurring in the tundish during the ladle change-over process have been proven detrimental to clean steel production.Therefore,an unsteady three-phase turbulence model,coupling velocity,temperature,and phase field was established to study the effect of the ladle shroud immersion depth on the slag eye formation,slag entrainment,slag dragging,air dragging,and flow characteristics during the ladle change-over process of a two-strand tundish.The results showed that reducing the immersion depth decreases the high-velocity region area under the slag layer in the quasi-steady process.During the emptying stage,as the molten bath level gradually decreases,the outlet temperature exhibits a trend of initially decreasing and subsequently increasing across all three shroud immersion depths.However,under a 210 mm shroud immersion depth,molten slag and air are dragged into the shroud,forming slag droplets and causing significant fluctuations,with a maximum scalar velocity of 0.0764 m/s at the monitoring point.In the filling stage,air and molten slag are dragged into the molten bath,forming bubbles and slag droplets at an immersion depth of 210 mm.Bubbles are observed within the molten slag layer,which can readily cause an emulsification phenomenon,making it easier to be dragged as slag droplets.Additionally,the slag eye area measured under 210 mm immersion depth at 45 s is 0.303 m^(2),while the maximum scalar velocity of 2.4259 m/s is detected at 12 s.At an immersion depth of 360 mm,the average area of the slag eye is minimized to 0.06268 m2,with corresponding variances of 0.006753,representing the optimal immersion depth.展开更多
Local resonant acoustic metamaterials have broad applications in sound insulation,yet their single-configuration designs often exhibit limited and discontinuous bandgap widths,hindering full-frequency noise attenuatio...Local resonant acoustic metamaterials have broad applications in sound insulation,yet their single-configuration designs often exhibit limited and discontinuous bandgap widths,hindering full-frequency noise attenuation across the human auditory range.This study presents a double-phase fidget-spinner-shaped acoustic metamaterial(DFAM),specifically designed to achieve an ultra-broad,low-frequency continuous bandgap by means of synergistic structural optimization,enabling effective and robust control of audible noise.Based on Bloch's theorem and the finite element method,the dispersion relation of the DFAM structure is calculated and verified by the transmission loss curves.The propagation characteristics of sound waves within the structure are further analyzed for noise frequencies that fall within the passband.The influence of the geometric and physical parameters on the bandgap is investigated,and the corresponding transmission loss in the propagation direction is further calculated.A hybrid collaborative design strategy,leveraging multi-parameter optimization and bandgap complementarity,is developed to construct a metastructure with continuous bandgap coverage from 20 Hz to 1000 Hz.The resulting metastructure demonstrates exceptional broadband noise attenuation,achieving a total bandgap width of 876.3 Hz(87.63% of the target range)with the transmission loss up to-762.78 d B in a three-periodic arrangement.The simulation and experimental results for the transmission loss of the DFAM metastructure show strong agreement in the low-frequency range.This work provides a novel framework for designing ultra-wide low-frequency continuous bandgap metastructures,offering significant potential for noise mitigation in complex environments.展开更多
A full-sectional microstructure characterization method was developed to investigate the formation of coarse slag rims during the continuous casting of hypo-peritectic steel.The cross-sectional microstructural analysi...A full-sectional microstructure characterization method was developed to investigate the formation of coarse slag rims during the continuous casting of hypo-peritectic steel.The cross-sectional microstructural analysis of typical slag rims for two highly crystalline powders revealed that their formation was primarily driven by the solidification of the liquid slag.Distinct differences were observed in the microstructures of slag rims from the two powders.Powder A(characterized by a higher breaking temperature and viscosity)displayed alternating lamellar microstructures of coarse and fine phases,with the coarse phases composed of akermanite-gehlenite transition phases.In contrast,powder B(with a lower breaking temperature and viscosity)predominantly comprised regular akermanite-gehlenite crystals interspersed with a certain amount of glassy phases.Numerical simulations of a three-phase fluid flow coupled with heat transfer indicate that slag rim formation correlates with mold oscillation.Solidification of the liquid slag at the slag rim front predominantly occurs during the negative stroke of the mold oscillation.The average heating rate during the ascending stage of the mold reaches approximately 100 K·s^(−1),whereas the average cooling rate during the descending stage attains 400 K·s^(−1).This temperature variation leads to the formation of lamellar microstructures,whereas the ascending stage promotes the formation of coarse structures and thicker slag rims.Based on the powder properties,two distinct formation pathways exist for highly crystalline mold powders.For the powders with a higher breaking temperature,higher viscosity,and narrower solidification range(powder A),coarse microstructures and thicker slag rims were preferentially formed.For powders with lower breaking temperature and viscosity and wider solidification ranges(powder B),the liquid slag resisted rapid solidification,and the extended mushy zone allowed the partial liquid slag to persist at the slag rim front,promoting the formation of a thin slag rim.This study enhances the understanding of slag rim formation in highly crystalline mold powders and provides critical insights into the control of longitudinal surface cracks in hypo-peritectic steel.展开更多
We report an immobilized enzyme-catalyzed batch and continuous-flow synthesis of optically pure ethyl(R)-pantothenate((R)-PaOEt),the direct precursor of d-pantothenic acid.Firstly,a ketoreductase mutant designated as ...We report an immobilized enzyme-catalyzed batch and continuous-flow synthesis of optically pure ethyl(R)-pantothenate((R)-PaOEt),the direct precursor of d-pantothenic acid.Firstly,a ketoreductase mutant designated as M2,carrying two-point mutations of F97L and M242F relative to the wild-type SSCR,was constructed by site-directed mutagenesis,exhibited simultaneously improved activity toward ethyl 2′-ketopantothenate(K-PaOEt)and isopropanol,and could effectively catalyze the stereoselective reduction of K-PaOEt to(R)-PaOEt by using isopropanol as the sacrificial co-substrate to regenerate NADPH.After screening six commercially available carriers,an amino resin LXTE-700 was identified as the best solid support for the immobilization of M2 via the glutaraldehyde activation method.Upon optimization of the immobilization process and reaction conditions,the fabricated immobilized enzyme M2@amino resin demonstrated excellent recyclability and reusability,with the complete conversion of K-PaOEt to(R)-PaOEt being still realized after 12 cycles of reuse.Finally,M2@amino resin-catalyzed synthesis of(R)-PaOEt was successfully implemented in continuous-flow,accomplishing a 6.3 times higher space-time yield than that with the batch synthesis(529.2 versus 84 g L^(-1) d^(-1)).Our developed flow biocatalysis system also features an outstanding operational stability,as evidenced by the 100%conversion rate achieved after 15 consecutive days of operation.展开更多
The rapid decay of the surface wettability of plasma-treated polymers remains a critical limitation for their practical application in advanced materials.This study introduces a continuous atmospheric pressure plasma(...The rapid decay of the surface wettability of plasma-treated polymers remains a critical limitation for their practical application in advanced materials.This study introduces a continuous atmospheric pressure plasma(APP)technique for fabricating polyethylene(PE)separators with durable wettability,and elucidates the underlying mechanism.A systematic comparison of APP treatments with non-deposition and deposition gases,including Ar,Ar/O_(2),Ar/tetramethylcyclotetrasiloxane(TMCTS),and Ar/O_(2)/TMCTS,revealed the key impact factors in achieving durable wettability.Owing to the synergistic interactions of SiO_(x)C_(y)H_(z)nanoparticulate deposition,physical etching,and oxidative functionalization,the PE separator treated by Ar/O_(2)/TMCTS exhibited a 17.5-fold electrolyte wetting area compared to the original one.The improved surface energy and roughness of the SiO_(x)C_(y)H_(z)nanoparticle coating enhanced its electrochemical performance.The ionic conductivity increased by 1.9 times,while the charge transfer resistance decreased by 73.7%.Remarkably,owing to further oxidation of the SiO_(x)C_(y)H_(z)nanoparticle coating and the increase in its silica-like structure,the wetting area of the Ar/O_(2)/TMCTS-treated separator was still over 14-fold larger than that of the original separator after aging for 90 days.This study demonstrates an eco-friendly and scalable approach for fabricating high-performance battery separators and provides mechanistic insights into durable wettability by APP.展开更多
The flow behavior of molten steel in the thin slab mold under high casting speed conditions was investigated,with a focus on the multi-mode continuous casting and rolling mold.A steel-slag two-phase flow model was est...The flow behavior of molten steel in the thin slab mold under high casting speed conditions was investigated,with a focus on the multi-mode continuous casting and rolling mold.A steel-slag two-phase flow model was established using large eddy simulation,the volume of fluid,and magnetohydrodynamics methods through numerical simulation.The maximum flow velocity and wave height at the steel-slag interface within the mold are critical evaluation criteria for analyzing asymmetric flow under varying casting speeds and electromagnetic braking.The results indicate that the asymmetric flows within the mold do not occur synchronously.The severity of the asymmetric flow correlates with the velocity difference across the steel-slag interface.A greater biased flow prolongs the time required to revert to a steady state.When the magnetic field intensity is set to 0.24 T and the magnetic pole position is at 390 mm from the steel-slag interface,this configuration can reduce the velocity of the steel-slag interface,thereby mitigating the asymmetric flow.Additionally,it can diminish the velocity,impact depth,and impact intensity on the narrow face of the jet,thus improving the distribution of velocity and turbulent kinetic energy within the mold.This configuration prolongs the time required for the steel-slag interface to transition from a stable state to its maximum velocity and shortens the time for the interface to return to stability from an unstable state.Moreover,it ensures the positional stability of the steel-slag interface,confining its position within−3 mm.展开更多
Under the background of achieving energy efficiency and carbon reduction,the use of Continuous Casting-Direct Hot Charging Rolling(CC-DHCR)technology was explored at the Hot Rolling Plant of Baosteel,China.As temperat...Under the background of achieving energy efficiency and carbon reduction,the use of Continuous Casting-Direct Hot Charging Rolling(CC-DHCR)technology was explored at the Hot Rolling Plant of Baosteel,China.As temperature variation and temperature uniformity directly affect the rolling quality of the billet,numerical simulations of the billet temperature profile changes in the CC-DHCR were conducted at the start of the industrial trial,and the billet temperature distribution and cross-section temperature difference during its transportation and throughout the heating process were analyzed.According to numerical simulation calculations,the average temperature of billet discharged from the heating furnace was 1150℃,which after subsequent controlled cooling met the final rolling temperature requirements of(880±30)℃for this kind of steel.The maximum temperature difference of the billet discharged from the furnace was within 35 K,which meets the billet heating uniformity requirements of the rolling process.The simulation results were compared with experimental results,and the rationality of the simulation was validated.In addition,the industrial trial billet was rolled,and the rolling quality was good during tracking.In this CC-DHCR industrial trial,the fuel consumption was 28.6 kgce/t(kilogram coal equivalent per ton),a reduction of 33.7%compared with the current traditional process,and CO 2 emissions were reduced by 38.09 kg/t.展开更多
Objective:To investigate the effects of switching to either Prandilin 25R monotherapy or Prandilin 25R combined with ganagliflozin proline tablets after short-term intensive continuous subcutaneous insulin infusion du...Objective:To investigate the effects of switching to either Prandilin 25R monotherapy or Prandilin 25R combined with ganagliflozin proline tablets after short-term intensive continuous subcutaneous insulin infusion during hospitalization in elderly patients with type 2 diabetes mellitus on glycemic control,glycometabolic indicators,and cardiovascular risk factors,and to evaluate the safety of the two regimens.Methods:A total of 78 elderly patients with type 2 diabetes mellitus admitted to our hospital from January 2025 to September 2025 were selected and randomly divided into a control group and an observation group,with 39 cases in each group.The control group received monotherapy with insulin lispro protamine recombinant injection(Prandilin 25R)after intensive continuous subcutaneous insulin infusion,while the observation group received Prandilin 25R combined with ganagliflozin proline tablets.Continuous glucose monitoring(CGM)was performed for 14 days during the intensive continuous subcutaneous insulin infusion therapy phase in the hospital,followed by routine fingertip blood glucose monitoring after 14 days.Glycemic control indicators,glycometabolic indicators,and the incidence of adverse reactions were compared between the two groups.Results:After treatment,the mean amplitude of glycemic excursions and the 24-hour blood glucose standard deviation were significantly lower in the observation group than in the control group,while the time spent within the target blood glucose range was significantly higher(p<0.05).The levels of glycated hemoglobin,fasting blood glucose,and 2-hour postprandial blood glucose were better in the observation group than in the control group;moreover,the body mass index,systolic blood pressure,and blood lipid levels improved more significantly in the observation group than in the control group(p<0.05).There was no statistically significant difference in the incidence of hypoglycemia between the two groups.Conclusion:Combination therapy with ganagliflozin proline tablets after short-term intensive continuous subcutaneous insulin infusion therapy can effectively improve glycemic variability in elderly patients with type 2 diabetes mellitus,with good safety.This suggests that ganagliflozin proline tablets have a hypoglycemic advantage in the combination regimen and possess high clinical promotional value.展开更多
基金supported by the National Natural Science Foundation of China(Nos.12372066,U23B6009,52171261)the Aeronautical Science Fund(No.20240013052002)the Qing Lan Project。
文摘The structural dynamic response reconstruction technology can extract unmeasured information from limited measured data,significantly impacting vibration control,load identification,parameter identification,fault diagnosis,and related fields.This paper proposes a dynamic response reconstruction method based on the Kalman filter,which simultaneously identifies external excitation and reconstructs dynamic responses at unmeasured positions.The weighted least squares method determines the load weighting matrix for excitation identification,while the minimum variance unbiased estimation determines the Kalman filter gain.The excitation prediction Kalman filter is constructed through time,excitation,and measurement updates.Subsequently,the response at the target point is reconstructed using the state vector,observation matrix,and excitation influence matrix obtained through the excitation prediction Kalman filter algorithm.An algorithm for reconstructing responses in continuous system using the excitation prediction Kalman filtering algorithm in modal space is derived.The proposed structural dynamic response reconstruction method evaluates the response reconstruction and the load identification performance under various load types and errors through simulation examples.Results demonstrate the accurate excitation identification under different load conditions and simultaneous reconstruction of target point responses,verifying the feasibility and reliability of the proposed method.
基金supported by the Scientific Research Innovation Development Foundation of Army Engineering University((2019)71).
文摘In this paper,a linear/nonlinear switching active disturbance rejection control(SADRC)based decoupling control approach is proposed to deal with some difficult control problems in a class of multi-input multi-output(MIMO)systems such as multi-variables,disturbances,and coupling,etc.Firstly,the structure and parameter tuning method of SADRC is introduced into this paper.Followed on this,virtual control variables are adopted into the MIMO systems,making the systems decoupled.Then the SADRC controller is designed for every subsystem.After this,a stability analyzed method via the Lyapunov function is proposed for the whole system.Finally,some simulations are presented to demonstrate the anti-disturbance and robustness of SADRC,and results show SADRC has a potential applications in engineering practice.
基金Supported by the National Natural Science Foundation of China(10771171)Supported by the 555 Innovation Talent Project of Gansu Province(GS-555-CXRC)+1 种基金Supported by the Technique Innovation Project of Northwest Normal University(NWNU-KJCXGC-212)Supported by the Youth Foundation of Dingxi Advanced Teachers College(1333)
文摘The functions of bounded φ-variation are development and generalization of bounded variation functions in the usual sense.Henstock-Kurzweil integral is a very useful tool for some discontinuous systems. In this paper, by using Henstock-Kurzweil integral, we establish theorems of continuous dependence of bounded D-variation solutions on parameter for a class of discontinuous systems on the base of D-function. These results are essential generalizations of continuous dependence of bounded variation solutions on parameter for the systems.
文摘An example is presented to introduce the concept of implicit continuity proposed as contrasted with the explicit continuity.A sufficient and necessary condition of the implicit continuity is given and proved in forms of implicit system.This condition also offers the solution of initial values at the points where the dynamic system is discontinuous.Some discussions are contributed to the physical significance of implicit continuity.
文摘Continuous System Simulation (CSS) is a powerful way to study the behaviour of differential-algebraic equation models. Differential-algebraic equation modelling goes back to Newton and works well for models of e.g. physical systems where stochasticity plays almost no role, and where only a single attribute of an object is studied over time. However, when results from a deterministic CSS model are compared with results from a Discrete Event Simulation (DES) model, they are often inconsistent. The reasons behind this CSS-DES inconsistency are nowadays well understood. In this paper, we demonstrate that a CSS model can contain both continuous state variables (compartments) that change continuously over time and discrete state variables (also compartments) that model discrete entities and change by integer amounts. In both cases, the time-slicing method is used to advance time. Furthermore, stochasticity can and should play the same role in CSS as it does in DES. This paper first explains how a well-defined conceptual model can be stepwise transformed in a consistent way into a CSS model. These transformation steps provide insights into how to construct a consistent CSS model. In short, this is about preserving uncertainties, attributes and dynamic properties. An additional benefit of this approach is that continuous and discrete sub-models can interact within the same model, without having to combine different types of simulation languages, types of time handling and incongruent concepts. To facilitate the use and understanding of stochastic CSS, this paper is also intended to serve as a guide to performing consistent CSS modelling and simulation. Furthermore, an open source tool for collecting and analyzing the outputs from a stochastic CSS model and analyzing and presenting the results in statistical form is also developed and made available to the reader.
基金supported by the National Natural Science Foundation of China(62433014,62373287,62573324,62333005,62273255)in part by the International Exchange Program for Graduate Students of Tongji University(4360143306)+3 种基金in part by the Fundamental Research Funds for Central Universities(22120230311)supported by DeutscheForschungsgemeinschaft(DFG,German Research Foundation)under Germany’s Excellence Strategy(EXC 2075390740016,468094890)support by the Stuttgart Center for Simulation Science(SimTech)the International Max Planck Research School for Intelligent Systems(IMPRS-IS)for supporting Y.Xie。
文摘Dear Editor,This letter proposes a reinforcement learning-based predictive learning algorithm for unknown continuous-time nonlinear systems with observation loss.Firstly,we construct a temporal nonzero-sum game over predictive control input sequences,deriving multiple optimal predictive control input sequences from its solution.
文摘Pediatric type 1 diabetes(T1D)is a lifelong condition requiring meticulous glucose management to prevent acute and chronic complications.Conventional management of diabetic patients does not allow for continuous monitoring of glucose trends,and can place patients at risk for hypo-and hyperglycemia.Continuous glucose monitors(CGMs)have emerged as a mainstay for pediatric diabetic care and are continuing to advance treatment by providing real-time blood glucose(BG)data,with trend analysis aided by machine learning(ML)algorithms.These predictive analytics serve to prevent against dangerous BG variations in the perioperative environment for fasted children undergoing surgical stress.Integration of CGM data into electronic health records(EHR)is essential,as it establishes a foundation for future technologic interfaces with artificial intelligence(AI).Challenges in perioperative CGM implementation include equitable device access,protection of patient privacy and data accuracy,ensuring institution of standardized protocols,and financing the cumbersome healthcare costs associated with staff training and technology platforms.This paper advocates for implementation of CGM data into the EHR utilizing multiple facets of AI/ML algorithms.
基金supported by the National Key Research and Development Program of China(2023YFD1700203and 2022YFD1901501)the Tianchi Talent Introduction Program of Xinjiang Autonomous Region,China(2023-“2+5”)the Tingzhou Talent Introduction Program of Changji Autonomous Region,China(2023)。
文摘Crops produced using the practice of continuous cropping can become seriously damaged by plant-parasitic nematodes,an important indicator of continuous cropping obstacles.As a typical and important perennial economic crop,dragon fruit is prone to serious plant-parasitic nematode infestation;however,whether it encounters continuous cropping obstacles remains unclear.Here,we studied plant-parasitic nematodes(Meloidogyne spp.and Tylenchorhynchus sp.)in the soil and roots,soil nematode communities,metabolic footprint,soil integrated fertility,and the yield of intensively planted dragon fruit under non-continuous cropping(Y1)and 3 years(Y3)and 5 years(Y5)of continuous cropping,to determine potential continuous-cropping obstacles and factors that affect the yield of this fruit.The largest numbers of plant-parasitic nematodes in the soil and roots were observed in Y5;the associated yield was reduced,and the dragon fruit was severely stressed.Further analysis of the composition,diversity,and ecological function indices of soil nematodes showed that the soil ecological environment deteriorated after 3 years of continuous cropping,with Y5 having the worst results.Similarly,the soil at Y5 had a significant inhibitory effect on the growth and reproduction of Caenorhabditis elegans.Mantel test analysis and a random forest model showed that soil available phosphorus,soil exchange calcium,and soil nematode abundance and diversity were related significantly to yield.Partial least squares path modeling revealed that soil fertility and soil nematode diversity directly impacts the yield of continuously cropped dragon fruit.In summary,continuous cropping obstacles occurred in Y5 of intensive dragon fruit cultivation,with soil nematode diversity and soil fertility determining the crop's yield.
基金supported by the Startup Foundation of Shenyang Agriculture University(No.X2023050)the Fundamental Research Funds for the Central Universities(No.N2209006)the National Natural Science Foundation of China(No.U22A20173).
文摘To address the current issues with the conventional slide gate system utilized in the steel teeming process,a unique electromagnetic induction controlled automated steel teeming(EICAST)technology has been developed.Cooling means of spiral coil in this technology is directly related to its service life.Firstly,heat transfer processes of air cooling and spray cooling were compared and analyzed.Secondly,the impacts of water temperature,water flow rate and air flow rate were examined in order to maximize the spray cooling effect.To maintain coil temperature at a low value consistently throughout the entire thermal cycle process of the ladle,a combined cooling mode was finally employed.Numerical simulation was applied to examine the coil temperature variation with different cooling systems and characteristics.Before coil operation,spray cooling is said to be more effective.By controlling the water flow rate and air flow rate,the spray cooling effect is enhanced.However,water temperature has little or no impact when using spray cooling.Air cooling during the secondary refining process and spray cooling prior to coil operation are combined to further lower coil temperature.When the direction of the spray cooling is from bottom to top,the coil temperature is lowered below 165℃.A practical induction coil cooling plan was provided for the EICAST technology’s production process.
基金supported in part by the Australian Research Council Discovery Project(DP190101557)
文摘To handle input and output time delays that commonly exist in many networked control systems(NCSs), a new robust continuous sliding mode control(CSMC) scheme is proposed for the output tracking in uncertain single input-single-output(SISO) networked control systems. This scheme consists of three consecutive steps. First, although the network-induced delay in those systems can be effectively handled by using Pade approximation(PA), the unmatched disturbance cames out as another difficulty in the control design. Second, to actively estimate this unmatched disturbance, a generalized proportional integral observer(GPIO) technique is utilized based on only one measured state. Third, by constructing a new sliding manifold with the aid of the estimated unmatched disturbance and states, a GPIO-based CSMC is synthesized, which is employed to cope with not only matched and unmatched disturbances, but also networkinduced delays. The stability of the entire closed-loop system under the proposed GPIO-based CSMC is detailedly analyzed.The promising tracking efficiency and feasibility of the proposed control methodology are verified through simulations and experiments on Quanser's servo module for motion control under various test conditions.
文摘1.Introduction.Pancreaticoduodenectomy is an essential surgical procedure for the treatment of malignant tumors in the pancreatic head,distal common bile duct,and duodenal papilla,and is widely used in clinical practice.One of the primary determinants of surgical success is the durability of the pancreaticojejunal anastomosis.
文摘Background:Continuous care for children with enterostomy and their families has been gaining popularity in China.Objective:To evaluate the feasibility of continuous care for children with enterostomy and their families in China.Methods:The PubMed,Web of Science,Embase,Cochrane Library,EBSCO,CNKI,CBM,VIP,and WanFang were searched for clinical trials until December 30,2025.Two reviewers independently searched articles,evaluated quality and extracted data.This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA).Results:33 studies involving 2774 participants were included.The meta-analysis showed that continuous care strategy can significantly reduce the incidence of complications in children with enterostomy(OR=0.20,95%CI=0.16-0.26,p<0.001,I2=0%),effectively improve the family caregiver ability for enterostomy(MD=-10.34,95%CI=-13.82 to-6.85,p<0.001,I2=99%),shorten the time for family members to replace stoma bags(MD=-13.57,95%CI=-19.66 to-7.49,p<0.001,I2=100%),and alleviate negative emotions such as anxiety(SMD=-1.80,95%CI=-2.36 to-1.23,p<0.001,I2=92%)and depression(SMD=-1.54,95%CI=-2.04 to-1.04,p<0.001,I2=89%)in the families of the affected children.Conclusions:Continuous care can reduce complications of enterostomy in children,improve the family caregiver ability for enterostomy and alleviate negative emotions of family members such as anxiety and depression.
基金supported by the National Natural Science Foundation of China(Nos.52422408 and 52171031)the Liaoning Xingliao Talents-Top-notch Young Talents Project(No.XLYC2203064)+1 种基金the Excellent Youth Fund of Liaoning Natural Science Foundation(No.2023JH3/10200001)the Fundamental Research Funds for the Central Universities(No.N2425004).
文摘The transient phenomena of re-oxidation and slag entrapment occurring in the tundish during the ladle change-over process have been proven detrimental to clean steel production.Therefore,an unsteady three-phase turbulence model,coupling velocity,temperature,and phase field was established to study the effect of the ladle shroud immersion depth on the slag eye formation,slag entrainment,slag dragging,air dragging,and flow characteristics during the ladle change-over process of a two-strand tundish.The results showed that reducing the immersion depth decreases the high-velocity region area under the slag layer in the quasi-steady process.During the emptying stage,as the molten bath level gradually decreases,the outlet temperature exhibits a trend of initially decreasing and subsequently increasing across all three shroud immersion depths.However,under a 210 mm shroud immersion depth,molten slag and air are dragged into the shroud,forming slag droplets and causing significant fluctuations,with a maximum scalar velocity of 0.0764 m/s at the monitoring point.In the filling stage,air and molten slag are dragged into the molten bath,forming bubbles and slag droplets at an immersion depth of 210 mm.Bubbles are observed within the molten slag layer,which can readily cause an emulsification phenomenon,making it easier to be dragged as slag droplets.Additionally,the slag eye area measured under 210 mm immersion depth at 45 s is 0.303 m^(2),while the maximum scalar velocity of 2.4259 m/s is detected at 12 s.At an immersion depth of 360 mm,the average area of the slag eye is minimized to 0.06268 m2,with corresponding variances of 0.006753,representing the optimal immersion depth.
基金Project supported by the National Natural Science Foundation of China(No.12572020)the Key Project of Natural Science Foundation of Hebei Province of China(No.A2023210064)。
文摘Local resonant acoustic metamaterials have broad applications in sound insulation,yet their single-configuration designs often exhibit limited and discontinuous bandgap widths,hindering full-frequency noise attenuation across the human auditory range.This study presents a double-phase fidget-spinner-shaped acoustic metamaterial(DFAM),specifically designed to achieve an ultra-broad,low-frequency continuous bandgap by means of synergistic structural optimization,enabling effective and robust control of audible noise.Based on Bloch's theorem and the finite element method,the dispersion relation of the DFAM structure is calculated and verified by the transmission loss curves.The propagation characteristics of sound waves within the structure are further analyzed for noise frequencies that fall within the passband.The influence of the geometric and physical parameters on the bandgap is investigated,and the corresponding transmission loss in the propagation direction is further calculated.A hybrid collaborative design strategy,leveraging multi-parameter optimization and bandgap complementarity,is developed to construct a metastructure with continuous bandgap coverage from 20 Hz to 1000 Hz.The resulting metastructure demonstrates exceptional broadband noise attenuation,achieving a total bandgap width of 876.3 Hz(87.63% of the target range)with the transmission loss up to-762.78 d B in a three-periodic arrangement.The simulation and experimental results for the transmission loss of the DFAM metastructure show strong agreement in the low-frequency range.This work provides a novel framework for designing ultra-wide low-frequency continuous bandgap metastructures,offering significant potential for noise mitigation in complex environments.
基金supported by the National Natural Science Foundation of China(No.52274318).
文摘A full-sectional microstructure characterization method was developed to investigate the formation of coarse slag rims during the continuous casting of hypo-peritectic steel.The cross-sectional microstructural analysis of typical slag rims for two highly crystalline powders revealed that their formation was primarily driven by the solidification of the liquid slag.Distinct differences were observed in the microstructures of slag rims from the two powders.Powder A(characterized by a higher breaking temperature and viscosity)displayed alternating lamellar microstructures of coarse and fine phases,with the coarse phases composed of akermanite-gehlenite transition phases.In contrast,powder B(with a lower breaking temperature and viscosity)predominantly comprised regular akermanite-gehlenite crystals interspersed with a certain amount of glassy phases.Numerical simulations of a three-phase fluid flow coupled with heat transfer indicate that slag rim formation correlates with mold oscillation.Solidification of the liquid slag at the slag rim front predominantly occurs during the negative stroke of the mold oscillation.The average heating rate during the ascending stage of the mold reaches approximately 100 K·s^(−1),whereas the average cooling rate during the descending stage attains 400 K·s^(−1).This temperature variation leads to the formation of lamellar microstructures,whereas the ascending stage promotes the formation of coarse structures and thicker slag rims.Based on the powder properties,two distinct formation pathways exist for highly crystalline mold powders.For the powders with a higher breaking temperature,higher viscosity,and narrower solidification range(powder A),coarse microstructures and thicker slag rims were preferentially formed.For powders with lower breaking temperature and viscosity and wider solidification ranges(powder B),the liquid slag resisted rapid solidification,and the extended mushy zone allowed the partial liquid slag to persist at the slag rim front,promoting the formation of a thin slag rim.This study enhances the understanding of slag rim formation in highly crystalline mold powders and provides critical insights into the control of longitudinal surface cracks in hypo-peritectic steel.
基金the Science and Technology R&D Major Project of Jiangxi Province(No.20244AFI92001)the National Natural Science Foundation of China(Nos.22071033 and 21801047)for the financial supports.
文摘We report an immobilized enzyme-catalyzed batch and continuous-flow synthesis of optically pure ethyl(R)-pantothenate((R)-PaOEt),the direct precursor of d-pantothenic acid.Firstly,a ketoreductase mutant designated as M2,carrying two-point mutations of F97L and M242F relative to the wild-type SSCR,was constructed by site-directed mutagenesis,exhibited simultaneously improved activity toward ethyl 2′-ketopantothenate(K-PaOEt)and isopropanol,and could effectively catalyze the stereoselective reduction of K-PaOEt to(R)-PaOEt by using isopropanol as the sacrificial co-substrate to regenerate NADPH.After screening six commercially available carriers,an amino resin LXTE-700 was identified as the best solid support for the immobilization of M2 via the glutaraldehyde activation method.Upon optimization of the immobilization process and reaction conditions,the fabricated immobilized enzyme M2@amino resin demonstrated excellent recyclability and reusability,with the complete conversion of K-PaOEt to(R)-PaOEt being still realized after 12 cycles of reuse.Finally,M2@amino resin-catalyzed synthesis of(R)-PaOEt was successfully implemented in continuous-flow,accomplishing a 6.3 times higher space-time yield than that with the batch synthesis(529.2 versus 84 g L^(-1) d^(-1)).Our developed flow biocatalysis system also features an outstanding operational stability,as evidenced by the 100%conversion rate achieved after 15 consecutive days of operation.
基金supported by the National Natural Science Foundation of China(No.12075054)the Fundamental Research Funds for the Central Universities(No.CUSF-DH-T-2024069)。
文摘The rapid decay of the surface wettability of plasma-treated polymers remains a critical limitation for their practical application in advanced materials.This study introduces a continuous atmospheric pressure plasma(APP)technique for fabricating polyethylene(PE)separators with durable wettability,and elucidates the underlying mechanism.A systematic comparison of APP treatments with non-deposition and deposition gases,including Ar,Ar/O_(2),Ar/tetramethylcyclotetrasiloxane(TMCTS),and Ar/O_(2)/TMCTS,revealed the key impact factors in achieving durable wettability.Owing to the synergistic interactions of SiO_(x)C_(y)H_(z)nanoparticulate deposition,physical etching,and oxidative functionalization,the PE separator treated by Ar/O_(2)/TMCTS exhibited a 17.5-fold electrolyte wetting area compared to the original one.The improved surface energy and roughness of the SiO_(x)C_(y)H_(z)nanoparticle coating enhanced its electrochemical performance.The ionic conductivity increased by 1.9 times,while the charge transfer resistance decreased by 73.7%.Remarkably,owing to further oxidation of the SiO_(x)C_(y)H_(z)nanoparticle coating and the increase in its silica-like structure,the wetting area of the Ar/O_(2)/TMCTS-treated separator was still over 14-fold larger than that of the original separator after aging for 90 days.This study demonstrates an eco-friendly and scalable approach for fabricating high-performance battery separators and provides mechanistic insights into durable wettability by APP.
基金support from the National Natural Science Foundation of China(Grant Nos.52174313 and 52304350)thank all members of the Hebei High Quality Steel Continuous Casting Engineering Technology Research Center at North China University of Science and Technology,Tangshan,China.
文摘The flow behavior of molten steel in the thin slab mold under high casting speed conditions was investigated,with a focus on the multi-mode continuous casting and rolling mold.A steel-slag two-phase flow model was established using large eddy simulation,the volume of fluid,and magnetohydrodynamics methods through numerical simulation.The maximum flow velocity and wave height at the steel-slag interface within the mold are critical evaluation criteria for analyzing asymmetric flow under varying casting speeds and electromagnetic braking.The results indicate that the asymmetric flows within the mold do not occur synchronously.The severity of the asymmetric flow correlates with the velocity difference across the steel-slag interface.A greater biased flow prolongs the time required to revert to a steady state.When the magnetic field intensity is set to 0.24 T and the magnetic pole position is at 390 mm from the steel-slag interface,this configuration can reduce the velocity of the steel-slag interface,thereby mitigating the asymmetric flow.Additionally,it can diminish the velocity,impact depth,and impact intensity on the narrow face of the jet,thus improving the distribution of velocity and turbulent kinetic energy within the mold.This configuration prolongs the time required for the steel-slag interface to transition from a stable state to its maximum velocity and shortens the time for the interface to return to stability from an unstable state.Moreover,it ensures the positional stability of the steel-slag interface,confining its position within−3 mm.
文摘Under the background of achieving energy efficiency and carbon reduction,the use of Continuous Casting-Direct Hot Charging Rolling(CC-DHCR)technology was explored at the Hot Rolling Plant of Baosteel,China.As temperature variation and temperature uniformity directly affect the rolling quality of the billet,numerical simulations of the billet temperature profile changes in the CC-DHCR were conducted at the start of the industrial trial,and the billet temperature distribution and cross-section temperature difference during its transportation and throughout the heating process were analyzed.According to numerical simulation calculations,the average temperature of billet discharged from the heating furnace was 1150℃,which after subsequent controlled cooling met the final rolling temperature requirements of(880±30)℃for this kind of steel.The maximum temperature difference of the billet discharged from the furnace was within 35 K,which meets the billet heating uniformity requirements of the rolling process.The simulation results were compared with experimental results,and the rationality of the simulation was validated.In addition,the industrial trial billet was rolled,and the rolling quality was good during tracking.In this CC-DHCR industrial trial,the fuel consumption was 28.6 kgce/t(kilogram coal equivalent per ton),a reduction of 33.7%compared with the current traditional process,and CO 2 emissions were reduced by 38.09 kg/t.
文摘Objective:To investigate the effects of switching to either Prandilin 25R monotherapy or Prandilin 25R combined with ganagliflozin proline tablets after short-term intensive continuous subcutaneous insulin infusion during hospitalization in elderly patients with type 2 diabetes mellitus on glycemic control,glycometabolic indicators,and cardiovascular risk factors,and to evaluate the safety of the two regimens.Methods:A total of 78 elderly patients with type 2 diabetes mellitus admitted to our hospital from January 2025 to September 2025 were selected and randomly divided into a control group and an observation group,with 39 cases in each group.The control group received monotherapy with insulin lispro protamine recombinant injection(Prandilin 25R)after intensive continuous subcutaneous insulin infusion,while the observation group received Prandilin 25R combined with ganagliflozin proline tablets.Continuous glucose monitoring(CGM)was performed for 14 days during the intensive continuous subcutaneous insulin infusion therapy phase in the hospital,followed by routine fingertip blood glucose monitoring after 14 days.Glycemic control indicators,glycometabolic indicators,and the incidence of adverse reactions were compared between the two groups.Results:After treatment,the mean amplitude of glycemic excursions and the 24-hour blood glucose standard deviation were significantly lower in the observation group than in the control group,while the time spent within the target blood glucose range was significantly higher(p<0.05).The levels of glycated hemoglobin,fasting blood glucose,and 2-hour postprandial blood glucose were better in the observation group than in the control group;moreover,the body mass index,systolic blood pressure,and blood lipid levels improved more significantly in the observation group than in the control group(p<0.05).There was no statistically significant difference in the incidence of hypoglycemia between the two groups.Conclusion:Combination therapy with ganagliflozin proline tablets after short-term intensive continuous subcutaneous insulin infusion therapy can effectively improve glycemic variability in elderly patients with type 2 diabetes mellitus,with good safety.This suggests that ganagliflozin proline tablets have a hypoglycemic advantage in the combination regimen and possess high clinical promotional value.