In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
Legume foods are not only trendy but also rich in nutrients and offer unique health benefits.Nevertheless,allergies to soy and other legumes have emerged as critical issues in food safety,presenting significant challe...Legume foods are not only trendy but also rich in nutrients and offer unique health benefits.Nevertheless,allergies to soy and other legumes have emerged as critical issues in food safety,presenting significant challenges to the food processing industry and impacting consumer health.The complexity of legume allergens,coupled with inadequate allergen identification methods and the absence of robust detection and evaluation systems,complicates the management of these allergens.Here,we provide a comprehensive and critical review,mentioning various aspects related to legume allergies,including the types of legume allergens,the mechanisms behind these allergies,and the immunoglobulin E(Ig E)-binding epitopes involved,summarizing and discussing the detection techniques and the impact of different processing techniques on sensitization to legume proteins.Furthermore,this paper provides an overview of research advances in diagnostic and therapeutic strategies for legume allergens and discusses current challenges and prospects for studying legume allergens.展开更多
Objective:To investigate the effects of“Three Methods and Three Acupoints”(TMTP)Tuina therapy on spinal microcirculation in sciatic nerve injury(SNI).Methods:Thirty-six SpragueeDawley rats were randomly assigned to ...Objective:To investigate the effects of“Three Methods and Three Acupoints”(TMTP)Tuina therapy on spinal microcirculation in sciatic nerve injury(SNI).Methods:Thirty-six SpragueeDawley rats were randomly assigned to four groups:normal,sham operation,model,and TMTP Tuina.Successful model induction was confirmed by observable hind limb lameness.After 20 sessions,hind limb grip strength and motor nerve conduction velocity(MNCV)were measured at baseline and following the 10th and 20th intervention.CD31 and a-SMA in the ventral horn of SNI model rats were detected using immunofluorescence.Motor neurons in the ventral horn were detected by Nissl staining.PTEN levels in the ventral horn were measured by ELISA,and PI3K,Akt,BDNF,VEGF,and HIF-1a expression was determined by RT-PCR.Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt,p-Akt,BDNF,and VEGF.Results:Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group(both P<.001).Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group,with increased expressions of a-SMA(P=.002)and CD31(P=.006).Western blot analysis indicated increased expression of VEGF(P=.005),p-Akt(P<.001),and BDNF(P=.008)in the ventral horn following Tuina treatment.RT-PCR analysis revealed increased expression of PI3K,Akt,BDNF,VEGF and HIF-1a(all P<.05).In contrast,expression of PTEN decreased compared to the model group(P<.001).Conclusion:TMTP Tuina therapy may restore motor function in rats,enhance ventral horn motor neuron morphology,and promote angiogenesis and vascular smooth muscle proliferation.The mechanism may involve the activation of the PI3K/Akt signaling pathway.展开更多
Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters accordi...Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters according to the monitoring data information in the structural health monitoring(SHM)system,so as to provide a scientific basis for structural damage identification and dynamic model modification.In view of this,this paper reviews methods for identifying structural modal parameters under environmental excitation and briefly describes how to identify structural damages based on the derived modal parameters.The paper primarily introduces data-driven modal parameter recognition methods(e.g.,time-domain,frequency-domain,and time-frequency-domain methods,etc.),briefly describes damage identification methods based on the variations of modal parameters(e.g.,natural frequency,modal shapes,and curvature modal shapes,etc.)and modal validation methods(e.g.,Stability Diagram and Modal Assurance Criterion,etc.).The current status of the application of artificial intelligence(AI)methods in the direction of modal parameter recognition and damage identification is further discussed.Based on the pre-vious analysis,the main development trends of structural modal parameter recognition and damage identification methods are given to provide scientific references for the optimized design and functional upgrading of SHM systems.展开更多
AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bo...AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.展开更多
The separation-of-variable(SOV)methods,such as the improved SOV method,the variational SOV method,and the extended SOV method,have been proposed by the present authors and coworkers to obtain the closed-form analytica...The separation-of-variable(SOV)methods,such as the improved SOV method,the variational SOV method,and the extended SOV method,have been proposed by the present authors and coworkers to obtain the closed-form analytical solutions for free vibration and eigenbuckling of rectangular plates and circular cylindrical shells.By taking the free vibration of rectangular thin plates as an example,this work presents the theoretical framework of the SOV methods in an instructive way,and the bisection–based solution procedures for a group of nonlinear eigenvalue equations.Besides,the explicit equations of nodal lines of the SOV methods are presented,and the relations of nodal line patterns and frequency orders are investigated.It is concluded that the highly accurate SOV methods have the same accuracy for all frequencies,the mode shapes about repeated frequencies can also be precisely captured,and the SOV methods do not have the problem of missing roots as well.展开更多
Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vi...Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vironment and intensify carbon emissions.However,the use of microbially induced calcium carbonate pre-cipitation(MICP)to obtain bio-cement is a novel technique with the potential to induce soil stability,providing a low-carbon,environment-friendly,and sustainable integrated solution for some geotechnical engineering pro-blems in the environment.This paper presents a comprehensive review of the latest progress in soil improvement based on the MICP strategy.It systematically summarizes and overviews the mineralization mechanism,influ-encing factors,improved methods,engineering characteristics,and current field application status of the MICP.Additionally,it also explores the limitations and correspondingly proposes prospective applications via the MICP approach for soil improvement.This review indicates that the utilization of different environmental calcium-based wastes in MICP and combination of materials and MICP are conducive to meeting engineering and market demand.Furthermore,we recommend and encourage global collaborative study and practice with a view to commercializing MICP technique in the future.The current review purports to provide insights for engineers and interdisciplinary researchers,and guidance for future engineering applications.展开更多
OBJECTIVE: To analyze the component law of Chinese medicines in fuming-washing therapy for knee osteoarthritis(KOA), and develop new fuming-washing prescriptions for KOA through unsupervised data mining methods.METHOD...OBJECTIVE: To analyze the component law of Chinese medicines in fuming-washing therapy for knee osteoarthritis(KOA), and develop new fuming-washing prescriptions for KOA through unsupervised data mining methods.METHODS: Chinese medicine recipes for fuming-washing therapy for KOA were collected and recorded in a database. The correlation coefficient among herbs, core combinations of herbs, andnew prescriptions were analyzed using modified mutual information, complex system entropy cluster, and unsupervised hierarchical clustering, respectively.RESULTS: Based on analysis of 345 Chinese medicine recipes for fuming-washing therapy, 68 herbs occurred frequently, 33 herb pairs occurred frequently, and 12 core combinations were found.Five new fuming-washing recipes for KOA were developed.CONCLUSION: Chinese medicines for fuming-washing therapy of KOA mainly consist of wind-dampness-dispelling and cold-dispersing herbs, blood-activating and stasis-resolving herbs,and wind-dampness-dispelling and heat-clearing herbs. The treatment of fuming-washing therapy for KOA also includes dispelling wind-dampness and dispersing cold, activating blood and resolving stasis, and dispelling wind-dampness and clearing heat. Zhenzhutougucao(Herba Speranskiae Tuberculatae), Honghua(Flos Carthami), Niuxi(Radix Achyranthis Bidentatae), Shenjincao(Herba Lycopodii Japonici), Weilingxian(Radix et Rhizoma Clematidis Chinensis), Chuanwu(Radix Aconiti), Haitongpi(Cortex Erythrinae Variegatae), Ruxiang(Olibanum),Danggui(Radix Angelicae Sinensis), Caowu(Radix Aconiti Kusnezoffii), Moyao(Myrrha), and Aiye(Folium Artemisiae Argyi) are the main herbs used in the fuming-washing treatment for KOA.展开更多
In order to solve the problem of the variable coefficient ordinary differen-tial equation on the bounded domain,the Lagrange interpolation method is used to approximate the exact solution of the equation,and the error...In order to solve the problem of the variable coefficient ordinary differen-tial equation on the bounded domain,the Lagrange interpolation method is used to approximate the exact solution of the equation,and the error between the numerical solution and the exact solution is obtained,and then compared with the error formed by the difference method,it is concluded that the Lagrange interpolation method is more effective in solving the variable coefficient ordinary differential equation.展开更多
Secondary vocational school students is different from ordinary high school students and university students,especially in the aspect of English teaching and learning.In view of the special career orientation of secon...Secondary vocational school students is different from ordinary high school students and university students,especially in the aspect of English teaching and learning.In view of the special career orientation of secondary vocational school education.English teaching methods in secondary vocational schools should have more practical and targeted. Used the Role Letter's Therapy in English teaching can help students develop interest in learning English and learning initiative consciousness. In this paper I will talk about the important of the Role Letter's Therapy in English teaching of Secondary vocational school,and how to use it.展开更多
Ocean energy has progressively gained considerable interest due to its sufficient potential to meet the world’s energy demand,and the blade is the core component in electricity generation from the ocean current.Howev...Ocean energy has progressively gained considerable interest due to its sufficient potential to meet the world’s energy demand,and the blade is the core component in electricity generation from the ocean current.However,the widened hydraulic excitation frequency may satisfy the blade resonance due to the time variation in the velocity and angle of attack of the ocean current,even resulting in blade fatigue and destructively interfering with grid stability.A key parameter that determines the resonance amplitude of the blade is the hydrodynamic damping ratio(HDR).However,HDR is difficult to obtain due to the complex fluid-structure interaction(FSI).Therefore,a literature review was conducted on the hydrodynamic damping characteristics of blade-like structures.The experimental and simulation methods used to identify and obtain the HDR quantitatively were described,placing emphasis on the experimental processes and simulation setups.Moreover,the accuracy and efficiency of different simulation methods were compared,and the modal work approach was recommended.The effects of key typical parameters,including flow velocity,angle of attack,gap,rotational speed,and cavitation,on the HDR were then summarized,and the suggestions on operating conditions were presented from the perspective of increasing the HDR.Subsequently,considering multiple flow parameters,several theoretical derivations and semi-empirical prediction formulas for HDR were introduced,and the accuracy and application were discussed.Based on the shortcomings of the existing research,the direction of future research was finally determined.The current work offers a clear understanding of the HDR of blade-like structures,which could improve the evaluation accuracy of flow-induced vibration in the design stage.展开更多
RNAs have important biological functions and the functions of RNAs are generally coupled to their structures, especiallytheir secondary structures. In this work, we have made a comprehensive evaluation of the performa...RNAs have important biological functions and the functions of RNAs are generally coupled to their structures, especiallytheir secondary structures. In this work, we have made a comprehensive evaluation of the performances of existingtop RNA secondary structure prediction methods, including five deep-learning (DL) based methods and five minimum freeenergy (MFE) based methods. First, we made a brief overview of these RNA secondary structure prediction methods.Afterwards, we built two rigorous test datasets consisting of RNAs with non-redundant sequences and comprehensivelyexamined the performances of the RNA secondary structure prediction methods through classifying the RNAs into differentlength ranges and different types. Our examination shows that the DL-based methods generally perform better thanthe MFE-based methods for RNAs with long lengths and complex structures, while the MFE-based methods can achievegood performance for small RNAs and some specialized MFE-based methods can achieve good prediction accuracy forpseudoknots. Finally, we provided some insights and perspectives in modeling RNA secondary structures.展开更多
Understanding the wind power potential of a site is essential for designing an optimal wind power conditioning system. The Weibull distribution and wind speed extrapolation methods are powerful mathematical tools for ...Understanding the wind power potential of a site is essential for designing an optimal wind power conditioning system. The Weibull distribution and wind speed extrapolation methods are powerful mathematical tools for efficiently predicting the frequency distribution of wind speeds at a site. Hourly wind speed and direction data were collected from the National Aeronautics and Space Administration (NASA) website for the period 2013 to 2023. MATLAB software was used to calculate the distribution parameters using the graphical method and to plot the corresponding curves, while WRPLOTView software was used to construct the wind rose. The average wind speed obtained is 3.33 m/s and can reach up to 5.71 m/s at a height of 100 meters. The wind energy is estimated to be 1315.30 kWh/m2 at a height of 100 meters. The wind rose indicates the prevailing winds (ranging from 3.60 m/s to 5.70 m/s) in the northeast-east direction.展开更多
Purpose–For the commonly used concrete mix for railway tunnel linings,concrete model specimens were made,and springback and core drilling tests were conducted at different ages.The springback strength was measured to...Purpose–For the commonly used concrete mix for railway tunnel linings,concrete model specimens were made,and springback and core drilling tests were conducted at different ages.The springback strength was measured to the compressive strength of the core sample with a diameter of 100mm and a height-to-diameter ratio of 1:1.By comparing the measured strength values,the relationship between the measured values under different strength measurement methods was analyzed.Design/methodology/approach–A comparative test of the core drilling method and the rebound method was conducted on the side walls of tunnel linings in some under-construction railways to study the feasibility of the rebound method in engineering quality supervision and inspection.Findings–Tests showed that the rebound strength was positively correlated with the core drill strength.The core drill test strength was significantly higher than the rebound test strength,and the strength still increased after 56 days of age.The rebound method is suitable for the general survey of concrete strength during the construction process and is not suitable for direct supervision and inspection.Originality/value–By studying the correlation of test strength of tunnel lining concrete using two methods,the differences in test results of different methods are proposed to provide a reference for the test and evaluation of tunnel lining strength in railway engineering.展开更多
BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent ...BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.展开更多
As pivotal supporting technologies for smart manufacturing and digital engineering,model-based and data-driven methods have been widely applied in many industrial fields,such as product design,process monitoring,and s...As pivotal supporting technologies for smart manufacturing and digital engineering,model-based and data-driven methods have been widely applied in many industrial fields,such as product design,process monitoring,and smart maintenance.While promising,both methods have issues that need to be addressed.For example,model-based methods are limited by low computational accuracy and a high computational burden,and data-driven methods always suffer from poor interpretability and redundant features.To address these issues,the concept of data-model fusion(DMF)emerges as a promising solution.DMF involves integrating model-based methods with data-driven methods by incorporating big data into model-based methods or embedding relevant domain knowledge into data-driven methods.Despite growing efforts in the field of DMF,a unanimous definition of DMF remains elusive,and a general framework of DMF has been rarely discussed.This paper aims to address this gap by providing a thorough overview and categorization of both data-driven methods and model-based methods.Subsequently,this paper also presents the definition and categorization of DMF and discusses the general framework of DMF.Moreover,the primary seven applications of DMF are reviewed within the context of smart manufacturing and digital engineering.Finally,this paper directs the future directions of DMF.展开更多
On the basis of the theory of Traditional Chinese Medicine,authors put forwathe etiopathogenesis and pathogenetic mechanism of solid tumors,and formulated a scheme for tre^ment of cancer with acupuncture therapy.
Efficient and accurate simulation of unsteady flow presents a significant challenge that needs to be overcome in computational fluid dynamics.Temporal discretization method plays a crucial role in the simulation of un...Efficient and accurate simulation of unsteady flow presents a significant challenge that needs to be overcome in computational fluid dynamics.Temporal discretization method plays a crucial role in the simulation of unsteady flows.To enhance computational efficiency,we propose the Implicit-Explicit Two-Step Runge-Kutta(IMEX-TSRK)time-stepping discretization methods for unsteady flows,and develop a novel adaptive algorithm that correctly partitions spatial regions to apply implicit or explicit methods.The novel adaptive IMEX-TSRK schemes effectively handle the numerical stiffness of the small grid size and improve computational efficiency.Compared to implicit and explicit Runge-Kutta(RK)schemes,the IMEX-TSRK methods achieve the same order of accuracy with fewer first derivative calculations.Numerical case tests demonstrate that the IMEX-TSRK methods maintain numerical stability while enhancing computational efficiency.Specifically,in high Reynolds number flows,the computational efficiency of the IMEX-TSRK methods surpasses that of explicit RK schemes by more than one order of magnitude,and that of implicit RK schemes several times over.展开更多
In this paper,a new technique is introduced to construct higher-order iterative methods for solving nonlinear systems.The order of convergence of some iterative methods can be improved by three at the cost of introduc...In this paper,a new technique is introduced to construct higher-order iterative methods for solving nonlinear systems.The order of convergence of some iterative methods can be improved by three at the cost of introducing only one additional evaluation of the function in each step.Furthermore,some new efficient methods with a higher-order of convergence are obtained by using only a single matrix inversion in each iteration.Analyses of convergence properties and computational efficiency of these new methods are made and testified by several numerical problems.By comparison,the new schemes are more efficient than the corresponding existing ones,particularly for large problem sizes.展开更多
The feasibility of using a problem-dependent method to solve systems of second order ODEs is corroborated by an eigen-based theory and a methodology to develop such a numerical method is constructed.The key steps of t...The feasibility of using a problem-dependent method to solve systems of second order ODEs is corroborated by an eigen-based theory and a methodology to develop such a numerical method is constructed.The key steps of this methodology are to decouple a system of ODEs of second order into a set of uncoupled ODEs of second order;next,an eigen-dependent method is proposed to approximate the solution of each uncoupled ODE of second order.It is vital to transform all eigen-dependent methods to a problem-dependent method to bypass an Eigen analysis.The development of an eigen-dependent method plays a key role in this methodology so that slow eigenmodes can be accurately integrated while there is no instability or excessive amplitude growth in fast eigenmodes.This can explain why a problem-dependent method can simultaneously combine the explicitness of each step and A-stability.Consequently,huge computational efforts can be saved for solving nonlinear stiff problems.A new family of problem-dependent methods is developed in this work so that the feasibility of the proposed methodology can be affirmed.It has almost the same performance as that of the HHT-αmethod.However,it can save more than 99.5%of CPU demand in approximating a solution for a system of 1000 nonlinear second order ODEs.展开更多
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
基金financially supported by National Natural Science Foundation of China(32460627 and 32272359)the Special Research Fund of Natural Science(Special Post)of Guizhou University(2022)54。
文摘Legume foods are not only trendy but also rich in nutrients and offer unique health benefits.Nevertheless,allergies to soy and other legumes have emerged as critical issues in food safety,presenting significant challenges to the food processing industry and impacting consumer health.The complexity of legume allergens,coupled with inadequate allergen identification methods and the absence of robust detection and evaluation systems,complicates the management of these allergens.Here,we provide a comprehensive and critical review,mentioning various aspects related to legume allergies,including the types of legume allergens,the mechanisms behind these allergies,and the immunoglobulin E(Ig E)-binding epitopes involved,summarizing and discussing the detection techniques and the impact of different processing techniques on sensitization to legume proteins.Furthermore,this paper provides an overview of research advances in diagnostic and therapeutic strategies for legume allergens and discusses current challenges and prospects for studying legume allergens.
基金supported by the National Natural Science Foundation of China(82274675&82074573)the Beijing Natural Science Foundation(7232278).
文摘Objective:To investigate the effects of“Three Methods and Three Acupoints”(TMTP)Tuina therapy on spinal microcirculation in sciatic nerve injury(SNI).Methods:Thirty-six SpragueeDawley rats were randomly assigned to four groups:normal,sham operation,model,and TMTP Tuina.Successful model induction was confirmed by observable hind limb lameness.After 20 sessions,hind limb grip strength and motor nerve conduction velocity(MNCV)were measured at baseline and following the 10th and 20th intervention.CD31 and a-SMA in the ventral horn of SNI model rats were detected using immunofluorescence.Motor neurons in the ventral horn were detected by Nissl staining.PTEN levels in the ventral horn were measured by ELISA,and PI3K,Akt,BDNF,VEGF,and HIF-1a expression was determined by RT-PCR.Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt,p-Akt,BDNF,and VEGF.Results:Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group(both P<.001).Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group,with increased expressions of a-SMA(P=.002)and CD31(P=.006).Western blot analysis indicated increased expression of VEGF(P=.005),p-Akt(P<.001),and BDNF(P=.008)in the ventral horn following Tuina treatment.RT-PCR analysis revealed increased expression of PI3K,Akt,BDNF,VEGF and HIF-1a(all P<.05).In contrast,expression of PTEN decreased compared to the model group(P<.001).Conclusion:TMTP Tuina therapy may restore motor function in rats,enhance ventral horn motor neuron morphology,and promote angiogenesis and vascular smooth muscle proliferation.The mechanism may involve the activation of the PI3K/Akt signaling pathway.
基金supported by the Innovation Foundation of Provincial Education Department of Gansu(2024B-005)the Gansu Province National Science Foundation(22YF7GA182)the Fundamental Research Funds for the Central Universities(No.lzujbky2022-kb01)。
文摘Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters according to the monitoring data information in the structural health monitoring(SHM)system,so as to provide a scientific basis for structural damage identification and dynamic model modification.In view of this,this paper reviews methods for identifying structural modal parameters under environmental excitation and briefly describes how to identify structural damages based on the derived modal parameters.The paper primarily introduces data-driven modal parameter recognition methods(e.g.,time-domain,frequency-domain,and time-frequency-domain methods,etc.),briefly describes damage identification methods based on the variations of modal parameters(e.g.,natural frequency,modal shapes,and curvature modal shapes,etc.)and modal validation methods(e.g.,Stability Diagram and Modal Assurance Criterion,etc.).The current status of the application of artificial intelligence(AI)methods in the direction of modal parameter recognition and damage identification is further discussed.Based on the pre-vious analysis,the main development trends of structural modal parameter recognition and damage identification methods are given to provide scientific references for the optimized design and functional upgrading of SHM systems.
文摘AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.
基金supported by the National Natural Science Foundation of China(12172023).
文摘The separation-of-variable(SOV)methods,such as the improved SOV method,the variational SOV method,and the extended SOV method,have been proposed by the present authors and coworkers to obtain the closed-form analytical solutions for free vibration and eigenbuckling of rectangular plates and circular cylindrical shells.By taking the free vibration of rectangular thin plates as an example,this work presents the theoretical framework of the SOV methods in an instructive way,and the bisection–based solution procedures for a group of nonlinear eigenvalue equations.Besides,the explicit equations of nodal lines of the SOV methods are presented,and the relations of nodal line patterns and frequency orders are investigated.It is concluded that the highly accurate SOV methods have the same accuracy for all frequencies,the mode shapes about repeated frequencies can also be precisely captured,and the SOV methods do not have the problem of missing roots as well.
基金funded by the National Natural Science Foundation of China(No.41962016)the Natural Science Foundation of NingXia(Nos.2023AAC02023,2023A1218,and 2021AAC02006).
文摘Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vironment and intensify carbon emissions.However,the use of microbially induced calcium carbonate pre-cipitation(MICP)to obtain bio-cement is a novel technique with the potential to induce soil stability,providing a low-carbon,environment-friendly,and sustainable integrated solution for some geotechnical engineering pro-blems in the environment.This paper presents a comprehensive review of the latest progress in soil improvement based on the MICP strategy.It systematically summarizes and overviews the mineralization mechanism,influ-encing factors,improved methods,engineering characteristics,and current field application status of the MICP.Additionally,it also explores the limitations and correspondingly proposes prospective applications via the MICP approach for soil improvement.This review indicates that the utilization of different environmental calcium-based wastes in MICP and combination of materials and MICP are conducive to meeting engineering and market demand.Furthermore,we recommend and encourage global collaborative study and practice with a view to commercializing MICP technique in the future.The current review purports to provide insights for engineers and interdisciplinary researchers,and guidance for future engineering applications.
基金Supported by Grant from the Administration of Traditional Chinese Medicine of Guangdong Province in China(No.20131161)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20124425110004)
文摘OBJECTIVE: To analyze the component law of Chinese medicines in fuming-washing therapy for knee osteoarthritis(KOA), and develop new fuming-washing prescriptions for KOA through unsupervised data mining methods.METHODS: Chinese medicine recipes for fuming-washing therapy for KOA were collected and recorded in a database. The correlation coefficient among herbs, core combinations of herbs, andnew prescriptions were analyzed using modified mutual information, complex system entropy cluster, and unsupervised hierarchical clustering, respectively.RESULTS: Based on analysis of 345 Chinese medicine recipes for fuming-washing therapy, 68 herbs occurred frequently, 33 herb pairs occurred frequently, and 12 core combinations were found.Five new fuming-washing recipes for KOA were developed.CONCLUSION: Chinese medicines for fuming-washing therapy of KOA mainly consist of wind-dampness-dispelling and cold-dispersing herbs, blood-activating and stasis-resolving herbs,and wind-dampness-dispelling and heat-clearing herbs. The treatment of fuming-washing therapy for KOA also includes dispelling wind-dampness and dispersing cold, activating blood and resolving stasis, and dispelling wind-dampness and clearing heat. Zhenzhutougucao(Herba Speranskiae Tuberculatae), Honghua(Flos Carthami), Niuxi(Radix Achyranthis Bidentatae), Shenjincao(Herba Lycopodii Japonici), Weilingxian(Radix et Rhizoma Clematidis Chinensis), Chuanwu(Radix Aconiti), Haitongpi(Cortex Erythrinae Variegatae), Ruxiang(Olibanum),Danggui(Radix Angelicae Sinensis), Caowu(Radix Aconiti Kusnezoffii), Moyao(Myrrha), and Aiye(Folium Artemisiae Argyi) are the main herbs used in the fuming-washing treatment for KOA.
文摘In order to solve the problem of the variable coefficient ordinary differen-tial equation on the bounded domain,the Lagrange interpolation method is used to approximate the exact solution of the equation,and the error between the numerical solution and the exact solution is obtained,and then compared with the error formed by the difference method,it is concluded that the Lagrange interpolation method is more effective in solving the variable coefficient ordinary differential equation.
文摘Secondary vocational school students is different from ordinary high school students and university students,especially in the aspect of English teaching and learning.In view of the special career orientation of secondary vocational school education.English teaching methods in secondary vocational schools should have more practical and targeted. Used the Role Letter's Therapy in English teaching can help students develop interest in learning English and learning initiative consciousness. In this paper I will talk about the important of the Role Letter's Therapy in English teaching of Secondary vocational school,and how to use it.
基金Supported by the National Natural Science Foundation of China(Nos.52222904 and 52309117)China Postdoctoral Science Foundation(Nos.2022TQ0168 and 2023M731895).
文摘Ocean energy has progressively gained considerable interest due to its sufficient potential to meet the world’s energy demand,and the blade is the core component in electricity generation from the ocean current.However,the widened hydraulic excitation frequency may satisfy the blade resonance due to the time variation in the velocity and angle of attack of the ocean current,even resulting in blade fatigue and destructively interfering with grid stability.A key parameter that determines the resonance amplitude of the blade is the hydrodynamic damping ratio(HDR).However,HDR is difficult to obtain due to the complex fluid-structure interaction(FSI).Therefore,a literature review was conducted on the hydrodynamic damping characteristics of blade-like structures.The experimental and simulation methods used to identify and obtain the HDR quantitatively were described,placing emphasis on the experimental processes and simulation setups.Moreover,the accuracy and efficiency of different simulation methods were compared,and the modal work approach was recommended.The effects of key typical parameters,including flow velocity,angle of attack,gap,rotational speed,and cavitation,on the HDR were then summarized,and the suggestions on operating conditions were presented from the perspective of increasing the HDR.Subsequently,considering multiple flow parameters,several theoretical derivations and semi-empirical prediction formulas for HDR were introduced,and the accuracy and application were discussed.Based on the shortcomings of the existing research,the direction of future research was finally determined.The current work offers a clear understanding of the HDR of blade-like structures,which could improve the evaluation accuracy of flow-induced vibration in the design stage.
基金supported by grants from the National Science Foundation of China(Grant Nos.12375038 and 12075171 to ZJT,and 12205223 to YLT).
文摘RNAs have important biological functions and the functions of RNAs are generally coupled to their structures, especiallytheir secondary structures. In this work, we have made a comprehensive evaluation of the performances of existingtop RNA secondary structure prediction methods, including five deep-learning (DL) based methods and five minimum freeenergy (MFE) based methods. First, we made a brief overview of these RNA secondary structure prediction methods.Afterwards, we built two rigorous test datasets consisting of RNAs with non-redundant sequences and comprehensivelyexamined the performances of the RNA secondary structure prediction methods through classifying the RNAs into differentlength ranges and different types. Our examination shows that the DL-based methods generally perform better thanthe MFE-based methods for RNAs with long lengths and complex structures, while the MFE-based methods can achievegood performance for small RNAs and some specialized MFE-based methods can achieve good prediction accuracy forpseudoknots. Finally, we provided some insights and perspectives in modeling RNA secondary structures.
文摘Understanding the wind power potential of a site is essential for designing an optimal wind power conditioning system. The Weibull distribution and wind speed extrapolation methods are powerful mathematical tools for efficiently predicting the frequency distribution of wind speeds at a site. Hourly wind speed and direction data were collected from the National Aeronautics and Space Administration (NASA) website for the period 2013 to 2023. MATLAB software was used to calculate the distribution parameters using the graphical method and to plot the corresponding curves, while WRPLOTView software was used to construct the wind rose. The average wind speed obtained is 3.33 m/s and can reach up to 5.71 m/s at a height of 100 meters. The wind energy is estimated to be 1315.30 kWh/m2 at a height of 100 meters. The wind rose indicates the prevailing winds (ranging from 3.60 m/s to 5.70 m/s) in the northeast-east direction.
文摘Purpose–For the commonly used concrete mix for railway tunnel linings,concrete model specimens were made,and springback and core drilling tests were conducted at different ages.The springback strength was measured to the compressive strength of the core sample with a diameter of 100mm and a height-to-diameter ratio of 1:1.By comparing the measured strength values,the relationship between the measured values under different strength measurement methods was analyzed.Design/methodology/approach–A comparative test of the core drilling method and the rebound method was conducted on the side walls of tunnel linings in some under-construction railways to study the feasibility of the rebound method in engineering quality supervision and inspection.Findings–Tests showed that the rebound strength was positively correlated with the core drill strength.The core drill test strength was significantly higher than the rebound test strength,and the strength still increased after 56 days of age.The rebound method is suitable for the general survey of concrete strength during the construction process and is not suitable for direct supervision and inspection.Originality/value–By studying the correlation of test strength of tunnel lining concrete using two methods,the differences in test results of different methods are proposed to provide a reference for the test and evaluation of tunnel lining strength in railway engineering.
基金Supported by The Science and Technology Plan Project of Guangzhou,No.202102010171National Natural Science Foundation。
文摘BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.
基金supported in part by the National Natural Science Foundation of China(NSFC)under Grants(52275471 and 52120105008)the Beijing Outstanding Young Scientist Program,and the New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘As pivotal supporting technologies for smart manufacturing and digital engineering,model-based and data-driven methods have been widely applied in many industrial fields,such as product design,process monitoring,and smart maintenance.While promising,both methods have issues that need to be addressed.For example,model-based methods are limited by low computational accuracy and a high computational burden,and data-driven methods always suffer from poor interpretability and redundant features.To address these issues,the concept of data-model fusion(DMF)emerges as a promising solution.DMF involves integrating model-based methods with data-driven methods by incorporating big data into model-based methods or embedding relevant domain knowledge into data-driven methods.Despite growing efforts in the field of DMF,a unanimous definition of DMF remains elusive,and a general framework of DMF has been rarely discussed.This paper aims to address this gap by providing a thorough overview and categorization of both data-driven methods and model-based methods.Subsequently,this paper also presents the definition and categorization of DMF and discusses the general framework of DMF.Moreover,the primary seven applications of DMF are reviewed within the context of smart manufacturing and digital engineering.Finally,this paper directs the future directions of DMF.
文摘On the basis of the theory of Traditional Chinese Medicine,authors put forwathe etiopathogenesis and pathogenetic mechanism of solid tumors,and formulated a scheme for tre^ment of cancer with acupuncture therapy.
基金supported by the National Natural Science Foundation of China(No.92252201)the Fundamental Research Funds for the Central Universitiesthe Academic Excellence Foundation of Beihang University(BUAA)for PhD Students。
文摘Efficient and accurate simulation of unsteady flow presents a significant challenge that needs to be overcome in computational fluid dynamics.Temporal discretization method plays a crucial role in the simulation of unsteady flows.To enhance computational efficiency,we propose the Implicit-Explicit Two-Step Runge-Kutta(IMEX-TSRK)time-stepping discretization methods for unsteady flows,and develop a novel adaptive algorithm that correctly partitions spatial regions to apply implicit or explicit methods.The novel adaptive IMEX-TSRK schemes effectively handle the numerical stiffness of the small grid size and improve computational efficiency.Compared to implicit and explicit Runge-Kutta(RK)schemes,the IMEX-TSRK methods achieve the same order of accuracy with fewer first derivative calculations.Numerical case tests demonstrate that the IMEX-TSRK methods maintain numerical stability while enhancing computational efficiency.Specifically,in high Reynolds number flows,the computational efficiency of the IMEX-TSRK methods surpasses that of explicit RK schemes by more than one order of magnitude,and that of implicit RK schemes several times over.
基金Supported by the National Natural Science Foundation of China(12061048)NSF of Jiangxi Province(20232BAB201026,20232BAB201018)。
文摘In this paper,a new technique is introduced to construct higher-order iterative methods for solving nonlinear systems.The order of convergence of some iterative methods can be improved by three at the cost of introducing only one additional evaluation of the function in each step.Furthermore,some new efficient methods with a higher-order of convergence are obtained by using only a single matrix inversion in each iteration.Analyses of convergence properties and computational efficiency of these new methods are made and testified by several numerical problems.By comparison,the new schemes are more efficient than the corresponding existing ones,particularly for large problem sizes.
文摘The feasibility of using a problem-dependent method to solve systems of second order ODEs is corroborated by an eigen-based theory and a methodology to develop such a numerical method is constructed.The key steps of this methodology are to decouple a system of ODEs of second order into a set of uncoupled ODEs of second order;next,an eigen-dependent method is proposed to approximate the solution of each uncoupled ODE of second order.It is vital to transform all eigen-dependent methods to a problem-dependent method to bypass an Eigen analysis.The development of an eigen-dependent method plays a key role in this methodology so that slow eigenmodes can be accurately integrated while there is no instability or excessive amplitude growth in fast eigenmodes.This can explain why a problem-dependent method can simultaneously combine the explicitness of each step and A-stability.Consequently,huge computational efforts can be saved for solving nonlinear stiff problems.A new family of problem-dependent methods is developed in this work so that the feasibility of the proposed methodology can be affirmed.It has almost the same performance as that of the HHT-αmethod.However,it can save more than 99.5%of CPU demand in approximating a solution for a system of 1000 nonlinear second order ODEs.
