Background Early embryo development plays a pivotal role in determining pregnancy outcomes,postnatal development,and lifelong health.Therefore,the strategic selection of functional nutrients to enhance embryo developm...Background Early embryo development plays a pivotal role in determining pregnancy outcomes,postnatal development,and lifelong health.Therefore,the strategic selection of functional nutrients to enhance embryo development is of paramount importance.In this study,we established a stable porcine trophectoderm cell line expressing dual fluorescent reporter genes driven by the CDX2 and TEAD4 gene promoter segments using lentiviral transfection.Results Three amino acid metabolites—kynurenic acid,taurine,and tryptamine—met the minimum z-score criteria of 2.0 for both luciferase and Renilla luciferase activities and were initially identified as potential metabolites for embryo development,with their beneficial effects validated by qPCR.Given that the identified metabolites are closely related to methionine,arginine,and tryptophan,we selected these three amino acids,using lysine as a standard,and employed response surface methodology combined with our high-throughput screening cell model to efficiently screen and optimize amino acid combination conducive to early embryo development.The optimized candidate amino acid system included lysine(1.87 mmol/L),methionine(0.82 mmol/L),tryptophan(0.23 mmol/L),and arginine(3 mmol/L),with the ratio of 1:0.43:0.12:1.60.In vitro experiments confirmed that this amino acid system enhances the expression of key genes involved in early embryonic development and improves in vitro embryo adhesion.Transcriptomic analysis of blastocysts suggested that candidate amino acid system enhances early embryo development by regulating early embryonic cell cycle and differentiation,as well as improving nutrient absorption.Furthermore,based on response surface methodology,400 sows were used to verify this amino acid system,substituting arginine with the more cost-effective N-carbamoyl glutamate(NCG),a precursor of arginine.The optimal dietary amino acid requirement was predicted to be 0.71%lysine,0.32%methionine,0.22%tryptophan,and 0.10%NCG for sows during early gestation.The optimized amino acid system ratio of the feed,derived from the peripheral release of essential amino acids,was found to be 1:0.45:0.13,which is largely consistent with the results obtained from the cell model optimization.Subsequently,we furtherly verified that this optimal dietary amino acid system significantly increased total litter size,live litter size and litter weight in sows.Conclusions In summary,we successfully established a dual-fluorescent high-throughput screening cell model for the efficient identification of potential nutrients that would promote embryo development and implantation.This innovative approach overcomes the limitations of traditional amino acid nutrition studies in sows,providing a more effective model for enhancing reproductive outcomes.展开更多
This paper introduces the conception of open complex giant system and the methodology for dealing with the system, with stress on its profound significance in development of science and technology. The authors conclud...This paper introduces the conception of open complex giant system and the methodology for dealing with the system, with stress on its profound significance in development of science and technology. The authors conclude that the reductionism underlying the exact science is not suitable to open complex giant system, and the only feasible alternative is the meta-synthetic engineering from the qualitative to the quantitative.展开更多
Unconventional oil and gas resources have become the most important and realistic field for increasing China’s domestic oil and gas reserves and production.At present,the production scale does not match the massive a...Unconventional oil and gas resources have become the most important and realistic field for increasing China’s domestic oil and gas reserves and production.At present,the production scale does not match the massive amount of resources and the rapid growth of proven geological reserves.The challenges of technology,cost,management,and methodology restrict large-scale and economic development.Based on successful practices,a"one engine with six gears"system engineering methodology is put forward,which includes life-cycle management,overall synergy,interdisciplinary cross-service integration,marketoriented operation,socialized support,digitalized management,and low-carbon and green development.The methodology has been proved to be effective in multiple unconventional oil and gas national demonstration areas,including the Jimusar continental shale oil demonstration area.Disruptive views are introduced-namely,that unconventional oil and gas do not necessarily yield a low return,nor do they necessarily have a low recovery factor.A determination to achieve economic benefit must be a pervasive underlying goal for managers and experts.Return and recovery factors,as primary focuses,must be adhered to during China’s development of unconventional oil and gas.The required methodology transformation includes a revolution in management systems to significantly decrease cost and increase production,resulting in technological innovation.展开更多
Background: The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019(COVID-19). Evaluating the quality of therapeutic data collected du...Background: The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019(COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances.Objective: To assess the methodological quality and variability in implementation of randomized controlled trials(RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation.Search strategy: Pub Med, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang,and Chongqing VIP, and the preprint repositories including Social Science Research Network and Med Rxiv were systematically searched, up to September 30, 2020, using the keywords "coronavirus disease 2019(COVID-19)," "2019 novel coronavirus(2019-n Co V)," "severe acute respiratory syndrome-related coronavirus-2(SARS-Co V-2)," "novel coronavirus pneumonia(NCP)," "randomized controlled trial(RCT)" and "random."Inclusion criteria: RCTs studying the treatment of COVID-19 were eligible for inclusion.Data extraction and analysis: Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions(Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information.Results: A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which,45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding.Conclusion: The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing highquality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.展开更多
In this paper,the symplectic perturbation series methodology of the non-conservative linear Hamiltonian system is presented for the structural dynamic response with damping.Firstly,the linear Hamiltonian system is bri...In this paper,the symplectic perturbation series methodology of the non-conservative linear Hamiltonian system is presented for the structural dynamic response with damping.Firstly,the linear Hamiltonian system is briefly introduced and its conservation law is proved based on the properties of the exterior products.Then the symplectic perturbation series methodology is proposed to deal with the non-conservative linear Hamiltonian system and its conservation law is further proved.The structural dynamic response problem with eternal load and damping is transformed as the non-conservative linear Hamiltonian system and the symplectic difference schemes for the non-conservative linear Hamiltonian system are established.The applicability and validity of the proposed method are demonstrated by three engineering examples.The results demonstrate that the presented methodology is better than the traditional Runge–Kutta algorithm in the prediction of long-time structural dynamic response under the same time step.展开更多
In this paper,a methodology for designing mooring system deployment for vessels at varying water depths is proposed.The Non-dominated Sorting Genetic Algorithm-II(NSGA-II)is combined with a self-dependently developed ...In this paper,a methodology for designing mooring system deployment for vessels at varying water depths is proposed.The Non-dominated Sorting Genetic Algorithm-II(NSGA-II)is combined with a self-dependently developed vessel-mooring coupled program to find the optimal mooring system deployment considering both station-keeping requirements and the safety of the mooring system.Two case studies are presented to demonstrate the methodology by designing the mooring system deployments for a very large floating structure(VLFS)module and a semi-submersible platform respectively at three different water depths.It can be concluded from the obtained results that the mooring system can achieve a better station-keeping ability with relatively shorter mooring line when deployed in the shallow water.The safety factor of mooring line is mainly dominated by the maximum instantaneous tension increment in the shallow water,while the pre-tension has a decisive influence on the safety factor of the mooring line in the deep water.展开更多
Goal oriented( GO) methodology is a kind of success oriented system reliability analysis method and has been used widely.The repairable system with dual input closed-loop feedback link( DICLFL) considering shutdown co...Goal oriented( GO) methodology is a kind of success oriented system reliability analysis method and has been used widely.The repairable system with dual input closed-loop feedback link( DICLFL) considering shutdown correlation didn't make reliability analysis accurately based on existing GO methodology. So, a reliability analysis method used to deal with DICLFL considering shutdown correlation is provided based on GO methodology.Firstly, a new operator, which is used to describe DICLFL considering shutdown correlation,whose number is 1,is created and named as Type 9C operator. And then,the formulas of type 9C operator are derived based on Markov process theory. Finally,the new method presented in this paper is adopted to conduct the reliability analysis of an electro-hydraulic servo speed control system. The analysis result is compared with those of Monte Carlo simulation and fault tree analysis( FTA). The comparison results show that this new reliability analysis method based on GO methodology is feasible and meaningful for reliability analysis of repairable systems with DICLFL considering shutdown correlation.Meantime,it will be useful for more other applications.展开更多
GO methodology is a success-oriented method for system reliability analysis. There are components with multi-fault modes in repairable systems. It is a problem to use the existing GO method to make reliability analysi...GO methodology is a success-oriented method for system reliability analysis. There are components with multi-fault modes in repairable systems. It is a problem to use the existing GO method to make reliability analysis of such repairable systems. A new GO method for reliability analysis of such repairable systems with multifault modes was presented. Firstly, calculation equations of reliability parameters of operators which were used to describe components with multi-fault modes in reparable systems were derived based on Markov process theory. Then, this new GO method was applied in reliability analysis of a hydraulic transmission oil supply system( HTOSS) of a power-shift steering transmission at low and high speeds. Finally,Compared with fault tree analysis( FTA) and Monte Carlo simulation,the results show that this new GO method is correct and suitable for reliability analysis of repairable system with multi-fault modes.展开更多
Objective:To extract,quantify,and evaluate the phenolic content in Opuntia ficus-indica skin for their antioxidant capacity with three different methods(ABTS,DPPH,and lipid oxidation)and to optimize the extraction con...Objective:To extract,quantify,and evaluate the phenolic content in Opuntia ficus-indica skin for their antioxidant capacity with three different methods(ABTS,DPPH,and lipid oxidation)and to optimize the extraction conditions[time,temperature and ethanol concentration)in a reflux system.Methods:The extraction process was done using a reflux system.A San CristobalⅡexperimental design with three variables and three levels was used.The variables evaluated were time of extraction(h),concentration of ethanol(%,v/v)and temperature(°C).The extraction process was optimized using a response surface methodology.Results:It was observed that at higher temperature more phenolic compounds were extracted,but the antioxidant capacity was decreased.The optimum conditions for phenolic compounds extraction and antioxidant capacity mixing the three methods were as Follows:45%of ethanol,80℃and 2 hours of extraction.Values obtained in our results are little higher that other previously reported.Conclusions:It can he concluded the by-products of Opuntia ficus-indica represent a good source of natural antioxidants with possible applications in food,cosmetics or drugs industries.展开更多
To improve the reliability of an aero-engine main fuel system, the quantitative and qualitative reliability analysis of the system is conducted based on goal oriented(GO) methodology. The quantitative reliability anal...To improve the reliability of an aero-engine main fuel system, the quantitative and qualitative reliability analysis of the system is conducted based on goal oriented(GO) methodology. The quantitative reliability analysis results and the minimum cut sets of the fuel system are obtained, respectively. These results are compared with the results of the FTA(Fault Tree Analysis) method, and the comparison result shows GO method is rational and applicable. Therefore, it is feasible to apply the GO method in the reliability analysis of an aero-engine main fuel system.展开更多
This paper presents an innovative Soft Design Science Methodology for improving information systems security using multi-layered security approach. The study applied Soft Design Science Methodology to address the prob...This paper presents an innovative Soft Design Science Methodology for improving information systems security using multi-layered security approach. The study applied Soft Design Science Methodology to address the problematic situation on how information systems security can be improved. In addition, Soft Design Science Methodology was compounded with mixed research methodology. This holistic approach helped for research methodology triangulation. The study assessed security requirements and developed a framework for improving information systems security. The study carried out maturity level assessment to determine security status quo in the education sector in Tanzania. The study identified security requirements gap (IT security controls, IT security measures) using ISO/IEC 21827: Systems Security Engineering-Capability Maturity Model (SSE-CMM) with a rating scale of 0 - 5. The results of this study show that maturity level across security domain is 0.44 out of 5. The finding shows that the implementation of IT security controls and security measures for ensuring security goals are lacking or conducted in ad-hoc. Thus, for improving the security of information systems, organisations should implement security controls and security measures in each security domain (multi-layer security). This research provides a framework for enhancing information systems security during capturing, processing, storage and transmission of information. This research has several practical contributions. Firstly, it contributes to the body of knowledge of information systems security by providing a set of security requirements for ensuring information systems security. Secondly, it contributes empirical evidence on how information systems security can be improved. Thirdly, it contributes on the applicability of Soft Design Science Methodology on addressing the problematic situation in information systems security. The research findings can be used by decision makers and lawmakers to improve existing cyber security laws, and enact laws for data privacy and sharing of open data.展开更多
This work presents the “Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology (2<sup>nd</sup>-CASAM)” for the efficient and exact computation of 1<sup>st</sup>- and 2<sup>...This work presents the “Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology (2<sup>nd</sup>-CASAM)” for the efficient and exact computation of 1<sup>st</sup>- and 2<sup>nd</sup>-order response sensitivities to uncertain parameters and domain boundaries of linear systems. The model’s response (<em>i.e.</em>, model result of interest) is a generic nonlinear function of the model’s forward and adjoint state functions, and also depends on the imprecisely known boundaries and model parameters. In the practically important particular case when the response is a scalar-valued functional of the forward and adjoint state functions characterizing a model comprising N parameters, the 2<sup>nd</sup>-CASAM requires a single large-scale computation using the First-Level Adjoint Sensitivity System (1<sup>st</sup>-LASS) for obtaining all of the first-order response sensitivities, and at most N large-scale computations using the Second-Level Adjoint Sensitivity System (2<sup>nd</sup>-LASS) for obtaining exactly all of the second-order response sensitivities. In contradistinction, forward other methods would require (<em>N</em>2/2 + 3 <em>N</em>/2) large-scale computations for obtaining all of the first- and second-order sensitivities. This work also shows that constructing and solving the 2<sup>nd</sup>-LASS requires very little additional effort beyond the construction of the 1<sup>st</sup>-LASS needed for computing the first-order sensitivities. Solving the equations underlying the 1<sup>st</sup>-LASS and 2<sup>nd</sup>-LASS requires the same computational solvers as needed for solving (<em>i.e.</em>, “inverting”) either the forward or the adjoint linear operators underlying the initial model. Therefore, the same computer software and “solvers” used for solving the original system of equations can also be used for solving the 1<sup>st</sup>-LASS and the 2<sup>nd</sup>-LASS. Since neither the 1<sup>st</sup>-LASS nor the 2<sup>nd</sup>-LASS involves any differentials of the operators underlying the original system, the 1<sup>st</sup>-LASS is designated as a “<u>first-level</u>” (as opposed to a “first-order”) adjoint sensitivity system, while the 2<sup>nd</sup>-LASS is designated as a “<u>second-level</u>” (rather than a “second-order”) adjoint sensitivity system. Mixed second-order response sensitivities involving boundary parameters may arise from all source terms of the 2<sup>nd</sup>-LASS that involve the imprecisely known boundary parameters. Notably, the 2<sup>nd</sup>-LASS encompasses an automatic, inherent, and independent “solution verification” mechanism of the correctness and accuracy of the 2nd-level adjoint functions needed for the efficient and exact computation of the second-order sensitivities.展开更多
Based on new analysis modes and new definitions with relative mathematization and simplification or strengthening forms for concepts of. generalized systems, panderivatives, pansymmetry, panbox principle, pansystems r...Based on new analysis modes and new definitions with relative mathematization and simplification or strengthening forms for concepts of. generalized systems, panderivatives, pansymmetry, panbox principle, pansystems relativity, etc., the framework and related principles of pansystems methodology and pansystems relativity are developed. Related contents include: pansystems with relatively universal mathematizing forms, 200 types of dualities, duality transformation, pansymmetry transformation, pansystems dialectics, the 8-domain method, pansystems mathematical methods, generalized quantification, the principles of approximation-transforming, pan-equivalence theorems, supply-demand analysis, thinking experiment, generalized gray systems, etc.展开更多
Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within t...Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within the realm of sports science and exercise medicine on the athletic gut microbiota.However,compared to other ergogenic aids and dietary supplements,probiotics present unique study challenges.The objectives of this systematic scoping review were to identify and characterize study methodologies of randomized controlled trials investigating supplementation with probiotics in athletes and physically active individuals.Methods:Four databases(MEDLINE,CINAHL,Cochrane CENTRAL,and Cochrane Database of Systematic Reviews)were searched for randomized controlled studies involving healthy athletes or physically active individuals.An intervention with probiotics and inclusion of a control and/or placebo group were essential.Only peer-reviewed articles in English were considered,and there were no date restrictions.Results were extracted and presented in tabular form to detail study protocols,characteristics,and outcomes.Bias in randomized controlled trials was determined with the RoB 2.0 tool.Results:A total of 45 studies were included in the review,with 35 using a parallel group design and 10 using a cross-over design.Approximately half the studies used a single probiotic and the other half a multi-strain preparation.The probiotic dose ranged from 2×10^(8)to 1×10^(11)colony forming units daily,and the length of intervention was between 7 and 150 days.Fewer than half the studies directly assessed gastrointestinal symptoms,gut permeability,or the gut microbiota.The sex ratio of participants was heavily weighted toward males,and only 3 studies exclusively investigated females.Low-level adverse events were reported in only 2 studies,although the methodology of reporting varied widely.The risk of bias was generally low,although details on randomization were lacking in some studies.Conclusion:There is a substantial body of research on the effects of prob iotic supplementation in healthy athletes and physically active individuals.Considerable heterogeneity in probiotic selection and dosage as well as outcome measures has made clinical and mechanistic interpretation challenging for both health care practitioners and researchers.Attention to issues of randomization of participants,treatments and interventions,selection of outcomes,demographics,and reporting of adverse events will facilitate more trustworthy interpretation of probiotic study results and inform evidence-based guidelines.展开更多
In a global dynamic analysis,the coexisting attractors and their basins are the main tools to understand the system behavior and safety.However,both basins and attractors can be drastically influenced by uncertainties...In a global dynamic analysis,the coexisting attractors and their basins are the main tools to understand the system behavior and safety.However,both basins and attractors can be drastically influenced by uncertainties.The aim of this work is to illustrate a methodology for the global dynamic analysis of nondeterministic dynamical systems with competing attractors.Accordingly,analytical and numerical tools for calculation of nondeterministic global structures,namely attractors and basins,are proposed.First,based on the definition of the Perron-Frobenius,Koopman and Foias linear operators,a global dynamic description through phase-space operators is presented for both deterministic and nondeterministic cases.In this context,the stochastic basins of attraction and attractors’distributions replace the usual basin and attractor concepts.Then,numerical implementation of these concepts is accomplished via an adaptative phase-space discretization strategy based on the classical Ulam method.Sample results of the methodology are presented for a canonical dynamical system.展开更多
Some patterns of refined epitomes of pansystems methodology were revealed roles and the related of them in problem-solving, modeling, algorithm-generating and theory-constructing were introduced. An important applicat...Some patterns of refined epitomes of pansystems methodology were revealed roles and the related of them in problem-solving, modeling, algorithm-generating and theory-constructing were introduced. An important application of pansystems methodology is to give some methods of constructing the typical pansymmetric-magic squares: 1. a method of recursively constructing magic squares of order n ( n greater than or equal to 5) ; 2. when magic squares of order m( m greater than or equal to 3) and magic squares of order n ( n greater than or equal to 3) are given of formula of obtaining magic squares of order nm; 3. when magic squares of order m ( m greater than or equal to 3) are given, a method of obtaining magic squares of order 2m.展开更多
This paper deals with the Self-Increasing-Difficulty system (SIDIS) separated from general systems, with emphasis on the relevant methodology based on the Spiral Combining Propulsion Principle (SPIPRO principle in sho...This paper deals with the Self-Increasing-Difficulty system (SIDIS) separated from general systems, with emphasis on the relevant methodology based on the Spiral Combining Propulsion Principle (SPIPRO principle in short). The system feature and its causative factors are analysed, and the implications and mechanism of the SPIPRO principle are discussed. Finally, the application possibilities of this methodology are illustrated with some examples.展开更多
Objective This study optimizes three-dimensional(3D) culture conditions of HepG2 using response surface methodology(RSM) based on the VitroGel system to facilitate the cell model in vitro for liver tissues.Method HepG...Objective This study optimizes three-dimensional(3D) culture conditions of HepG2 using response surface methodology(RSM) based on the VitroGel system to facilitate the cell model in vitro for liver tissues.Method HepG2 cell was 3D cultured on the VitroGel system.Cell viability was detected using Cell Counting Kit-8(CCK-8) assay of HepG2 lived cell numbers.The proliferation of HepG2 cell and clustering performance was measured via fluorescence staining test.Albumin concentration in the culture medium supernatant as an index of HepG2 cell biological function was measured with ELISA kit.Independent factor tests were conducted with three key factors:inoculated cell concentration,cultured time,and dilution degree of the hydrogel.The preliminary results of independent factor tests were used to determine the levels of factors for RSM.Result The selected optimal culture conditions are as follows:concentration of inoculated cells was4.44 × 10^(5)/mL,culture time was 4.86 days,and hydrogel dilution degree was 1:2.23.The result shows that under optimal conditions,the predicted optical density(OD) value of cell viability was 3.10 and measured 2.978 with a relative error of 3.94%.Conclusion This study serves as a reference for the 3D HepG2 culture and constructs liver tissues in vitro.Additionally,it provides the foundation for repeated dose high-throughput toxicity studies and other scientific research work.展开更多
In this paper,the network reliability of an actual digital instrument and control system (DICS) network is analyzed by using GO-FLOW methodology (GFM).The evaluations of common-cause failure (CCF) and uncertainty are ...In this paper,the network reliability of an actual digital instrument and control system (DICS) network is analyzed by using GO-FLOW methodology (GFM).The evaluations of common-cause failure (CCF) and uncertainty are incorporated.Three significant CCF groups (real time servers,gateways,reactor protection system) and three typical time intervals (10 min,1 h,and 24 h) are selected in the analysis.It is concluded that the network contribution of CCF accounts for over 68% of the system failure probability.The result indicates that GFM is suitable for the network reliability analysis.展开更多
This work investigates coag-flocculation optimization treatment of alum-brewery effluent system via response surface methodology (RSM). To minimize suspended and dissolved particles (SDP), experiments were carried out...This work investigates coag-flocculation optimization treatment of alum-brewery effluent system via response surface methodology (RSM). To minimize suspended and dissolved particles (SDP), experiments were carried out using nephelometric jar test and 23-factorial design with three star-points, six-center-points and two replications. A central composite design, which is the standard design of RSM, was used to evaluate the effects and interactions of three major factors (coagulation pH, coagulant dosage, settling time) on the treatment efficiency. Multivariable quadratic model developed for the response studied indicates the optimum conditions to be 9, 500mg/l and 20minutes for coagulation pH, coagulant dosage and settling time, respectively. At optimum, the SDP was reduced from 10831.490mg/l to 801.451mg/l, representing 92.601% removal efficiency. RSM has demonstrated to be appropriate approach for the optimization of the coag-flocculation process by statistical evaluation.展开更多
基金supported by National Natural Science Foundation of China (32172747 and 32425052)
文摘Background Early embryo development plays a pivotal role in determining pregnancy outcomes,postnatal development,and lifelong health.Therefore,the strategic selection of functional nutrients to enhance embryo development is of paramount importance.In this study,we established a stable porcine trophectoderm cell line expressing dual fluorescent reporter genes driven by the CDX2 and TEAD4 gene promoter segments using lentiviral transfection.Results Three amino acid metabolites—kynurenic acid,taurine,and tryptamine—met the minimum z-score criteria of 2.0 for both luciferase and Renilla luciferase activities and were initially identified as potential metabolites for embryo development,with their beneficial effects validated by qPCR.Given that the identified metabolites are closely related to methionine,arginine,and tryptophan,we selected these three amino acids,using lysine as a standard,and employed response surface methodology combined with our high-throughput screening cell model to efficiently screen and optimize amino acid combination conducive to early embryo development.The optimized candidate amino acid system included lysine(1.87 mmol/L),methionine(0.82 mmol/L),tryptophan(0.23 mmol/L),and arginine(3 mmol/L),with the ratio of 1:0.43:0.12:1.60.In vitro experiments confirmed that this amino acid system enhances the expression of key genes involved in early embryonic development and improves in vitro embryo adhesion.Transcriptomic analysis of blastocysts suggested that candidate amino acid system enhances early embryo development by regulating early embryonic cell cycle and differentiation,as well as improving nutrient absorption.Furthermore,based on response surface methodology,400 sows were used to verify this amino acid system,substituting arginine with the more cost-effective N-carbamoyl glutamate(NCG),a precursor of arginine.The optimal dietary amino acid requirement was predicted to be 0.71%lysine,0.32%methionine,0.22%tryptophan,and 0.10%NCG for sows during early gestation.The optimized amino acid system ratio of the feed,derived from the peripheral release of essential amino acids,was found to be 1:0.45:0.13,which is largely consistent with the results obtained from the cell model optimization.Subsequently,we furtherly verified that this optimal dietary amino acid system significantly increased total litter size,live litter size and litter weight in sows.Conclusions In summary,we successfully established a dual-fluorescent high-throughput screening cell model for the efficient identification of potential nutrients that would promote embryo development and implantation.This innovative approach overcomes the limitations of traditional amino acid nutrition studies in sows,providing a more effective model for enhancing reproductive outcomes.
文摘This paper introduces the conception of open complex giant system and the methodology for dealing with the system, with stress on its profound significance in development of science and technology. The authors conclude that the reductionism underlying the exact science is not suitable to open complex giant system, and the only feasible alternative is the meta-synthetic engineering from the qualitative to the quantitative.
基金supported by the Project of Basic Science Center for the National Natural Science Foundation of China(72088101)。
文摘Unconventional oil and gas resources have become the most important and realistic field for increasing China’s domestic oil and gas reserves and production.At present,the production scale does not match the massive amount of resources and the rapid growth of proven geological reserves.The challenges of technology,cost,management,and methodology restrict large-scale and economic development.Based on successful practices,a"one engine with six gears"system engineering methodology is put forward,which includes life-cycle management,overall synergy,interdisciplinary cross-service integration,marketoriented operation,socialized support,digitalized management,and low-carbon and green development.The methodology has been proved to be effective in multiple unconventional oil and gas national demonstration areas,including the Jimusar continental shale oil demonstration area.Disruptive views are introduced-namely,that unconventional oil and gas do not necessarily yield a low return,nor do they necessarily have a low recovery factor.A determination to achieve economic benefit must be a pervasive underlying goal for managers and experts.Return and recovery factors,as primary focuses,must be adhered to during China’s development of unconventional oil and gas.The required methodology transformation includes a revolution in management systems to significantly decrease cost and increase production,resulting in technological innovation.
基金supported by the National Key R&D Program of China(2019YFC1710400,2019YFC1710405)the National Natural Science Foundation of China(No.81803963)。
文摘Background: The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019(COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances.Objective: To assess the methodological quality and variability in implementation of randomized controlled trials(RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation.Search strategy: Pub Med, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang,and Chongqing VIP, and the preprint repositories including Social Science Research Network and Med Rxiv were systematically searched, up to September 30, 2020, using the keywords "coronavirus disease 2019(COVID-19)," "2019 novel coronavirus(2019-n Co V)," "severe acute respiratory syndrome-related coronavirus-2(SARS-Co V-2)," "novel coronavirus pneumonia(NCP)," "randomized controlled trial(RCT)" and "random."Inclusion criteria: RCTs studying the treatment of COVID-19 were eligible for inclusion.Data extraction and analysis: Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions(Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information.Results: A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which,45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding.Conclusion: The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing highquality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.
基金This work was supported by the National Nature Science Foundation of China(Grant 11772026)Defense Industrial Technology Development Program(Grants JCKY2017208B001 and JCKY2018601B001)Beijing Municipal Science and Technology Commission via project(Grant Z191100004619006),and Beijing Advanced Discipline Center for Unmanned Aircraft System.
文摘In this paper,the symplectic perturbation series methodology of the non-conservative linear Hamiltonian system is presented for the structural dynamic response with damping.Firstly,the linear Hamiltonian system is briefly introduced and its conservation law is proved based on the properties of the exterior products.Then the symplectic perturbation series methodology is proposed to deal with the non-conservative linear Hamiltonian system and its conservation law is further proved.The structural dynamic response problem with eternal load and damping is transformed as the non-conservative linear Hamiltonian system and the symplectic difference schemes for the non-conservative linear Hamiltonian system are established.The applicability and validity of the proposed method are demonstrated by three engineering examples.The results demonstrate that the presented methodology is better than the traditional Runge–Kutta algorithm in the prediction of long-time structural dynamic response under the same time step.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.51709170 and 51979167)the Ministry of Industry and Information Technology of China(Mooring position technology:floating support platform engineering(II))the Shanghai Sailing Program(Grant No.17YF1409700)
文摘In this paper,a methodology for designing mooring system deployment for vessels at varying water depths is proposed.The Non-dominated Sorting Genetic Algorithm-II(NSGA-II)is combined with a self-dependently developed vessel-mooring coupled program to find the optimal mooring system deployment considering both station-keeping requirements and the safety of the mooring system.Two case studies are presented to demonstrate the methodology by designing the mooring system deployments for a very large floating structure(VLFS)module and a semi-submersible platform respectively at three different water depths.It can be concluded from the obtained results that the mooring system can achieve a better station-keeping ability with relatively shorter mooring line when deployed in the shallow water.The safety factor of mooring line is mainly dominated by the maximum instantaneous tension increment in the shallow water,while the pre-tension has a decisive influence on the safety factor of the mooring line in the deep water.
基金Technical Basis Projects of China's MIIT(Nos.ZQ092012B003,2012090003)
文摘Goal oriented( GO) methodology is a kind of success oriented system reliability analysis method and has been used widely.The repairable system with dual input closed-loop feedback link( DICLFL) considering shutdown correlation didn't make reliability analysis accurately based on existing GO methodology. So, a reliability analysis method used to deal with DICLFL considering shutdown correlation is provided based on GO methodology.Firstly, a new operator, which is used to describe DICLFL considering shutdown correlation,whose number is 1,is created and named as Type 9C operator. And then,the formulas of type 9C operator are derived based on Markov process theory. Finally,the new method presented in this paper is adopted to conduct the reliability analysis of an electro-hydraulic servo speed control system. The analysis result is compared with those of Monte Carlo simulation and fault tree analysis( FTA). The comparison results show that this new reliability analysis method based on GO methodology is feasible and meaningful for reliability analysis of repairable systems with DICLFL considering shutdown correlation.Meantime,it will be useful for more other applications.
基金Technical Basis Projects of China's MIIT(No.2012090003)
文摘GO methodology is a success-oriented method for system reliability analysis. There are components with multi-fault modes in repairable systems. It is a problem to use the existing GO method to make reliability analysis of such repairable systems. A new GO method for reliability analysis of such repairable systems with multifault modes was presented. Firstly, calculation equations of reliability parameters of operators which were used to describe components with multi-fault modes in reparable systems were derived based on Markov process theory. Then, this new GO method was applied in reliability analysis of a hydraulic transmission oil supply system( HTOSS) of a power-shift steering transmission at low and high speeds. Finally,Compared with fault tree analysis( FTA) and Monte Carlo simulation,the results show that this new GO method is correct and suitable for reliability analysis of repairable system with multi-fault modes.
基金Supported by the Universidad Autonoma de Coahuila and the Consejo Nacional de Ciencia y Tecnologia(CONACYT).Grant number:COAH-2010C13-147563
文摘Objective:To extract,quantify,and evaluate the phenolic content in Opuntia ficus-indica skin for their antioxidant capacity with three different methods(ABTS,DPPH,and lipid oxidation)and to optimize the extraction conditions[time,temperature and ethanol concentration)in a reflux system.Methods:The extraction process was done using a reflux system.A San CristobalⅡexperimental design with three variables and three levels was used.The variables evaluated were time of extraction(h),concentration of ethanol(%,v/v)and temperature(°C).The extraction process was optimized using a response surface methodology.Results:It was observed that at higher temperature more phenolic compounds were extracted,but the antioxidant capacity was decreased.The optimum conditions for phenolic compounds extraction and antioxidant capacity mixing the three methods were as Follows:45%of ethanol,80℃and 2 hours of extraction.Values obtained in our results are little higher that other previously reported.Conclusions:It can he concluded the by-products of Opuntia ficus-indica represent a good source of natural antioxidants with possible applications in food,cosmetics or drugs industries.
基金the Shenyang Engine Research Institute,Aero Engine Corporation of China(No.A0920132002)
文摘To improve the reliability of an aero-engine main fuel system, the quantitative and qualitative reliability analysis of the system is conducted based on goal oriented(GO) methodology. The quantitative reliability analysis results and the minimum cut sets of the fuel system are obtained, respectively. These results are compared with the results of the FTA(Fault Tree Analysis) method, and the comparison result shows GO method is rational and applicable. Therefore, it is feasible to apply the GO method in the reliability analysis of an aero-engine main fuel system.
文摘This paper presents an innovative Soft Design Science Methodology for improving information systems security using multi-layered security approach. The study applied Soft Design Science Methodology to address the problematic situation on how information systems security can be improved. In addition, Soft Design Science Methodology was compounded with mixed research methodology. This holistic approach helped for research methodology triangulation. The study assessed security requirements and developed a framework for improving information systems security. The study carried out maturity level assessment to determine security status quo in the education sector in Tanzania. The study identified security requirements gap (IT security controls, IT security measures) using ISO/IEC 21827: Systems Security Engineering-Capability Maturity Model (SSE-CMM) with a rating scale of 0 - 5. The results of this study show that maturity level across security domain is 0.44 out of 5. The finding shows that the implementation of IT security controls and security measures for ensuring security goals are lacking or conducted in ad-hoc. Thus, for improving the security of information systems, organisations should implement security controls and security measures in each security domain (multi-layer security). This research provides a framework for enhancing information systems security during capturing, processing, storage and transmission of information. This research has several practical contributions. Firstly, it contributes to the body of knowledge of information systems security by providing a set of security requirements for ensuring information systems security. Secondly, it contributes empirical evidence on how information systems security can be improved. Thirdly, it contributes on the applicability of Soft Design Science Methodology on addressing the problematic situation in information systems security. The research findings can be used by decision makers and lawmakers to improve existing cyber security laws, and enact laws for data privacy and sharing of open data.
文摘This work presents the “Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology (2<sup>nd</sup>-CASAM)” for the efficient and exact computation of 1<sup>st</sup>- and 2<sup>nd</sup>-order response sensitivities to uncertain parameters and domain boundaries of linear systems. The model’s response (<em>i.e.</em>, model result of interest) is a generic nonlinear function of the model’s forward and adjoint state functions, and also depends on the imprecisely known boundaries and model parameters. In the practically important particular case when the response is a scalar-valued functional of the forward and adjoint state functions characterizing a model comprising N parameters, the 2<sup>nd</sup>-CASAM requires a single large-scale computation using the First-Level Adjoint Sensitivity System (1<sup>st</sup>-LASS) for obtaining all of the first-order response sensitivities, and at most N large-scale computations using the Second-Level Adjoint Sensitivity System (2<sup>nd</sup>-LASS) for obtaining exactly all of the second-order response sensitivities. In contradistinction, forward other methods would require (<em>N</em>2/2 + 3 <em>N</em>/2) large-scale computations for obtaining all of the first- and second-order sensitivities. This work also shows that constructing and solving the 2<sup>nd</sup>-LASS requires very little additional effort beyond the construction of the 1<sup>st</sup>-LASS needed for computing the first-order sensitivities. Solving the equations underlying the 1<sup>st</sup>-LASS and 2<sup>nd</sup>-LASS requires the same computational solvers as needed for solving (<em>i.e.</em>, “inverting”) either the forward or the adjoint linear operators underlying the initial model. Therefore, the same computer software and “solvers” used for solving the original system of equations can also be used for solving the 1<sup>st</sup>-LASS and the 2<sup>nd</sup>-LASS. Since neither the 1<sup>st</sup>-LASS nor the 2<sup>nd</sup>-LASS involves any differentials of the operators underlying the original system, the 1<sup>st</sup>-LASS is designated as a “<u>first-level</u>” (as opposed to a “first-order”) adjoint sensitivity system, while the 2<sup>nd</sup>-LASS is designated as a “<u>second-level</u>” (rather than a “second-order”) adjoint sensitivity system. Mixed second-order response sensitivities involving boundary parameters may arise from all source terms of the 2<sup>nd</sup>-LASS that involve the imprecisely known boundary parameters. Notably, the 2<sup>nd</sup>-LASS encompasses an automatic, inherent, and independent “solution verification” mechanism of the correctness and accuracy of the 2nd-level adjoint functions needed for the efficient and exact computation of the second-order sensitivities.
文摘Based on new analysis modes and new definitions with relative mathematization and simplification or strengthening forms for concepts of. generalized systems, panderivatives, pansymmetry, panbox principle, pansystems relativity, etc., the framework and related principles of pansystems methodology and pansystems relativity are developed. Related contents include: pansystems with relatively universal mathematizing forms, 200 types of dualities, duality transformation, pansymmetry transformation, pansystems dialectics, the 8-domain method, pansystems mathematical methods, generalized quantification, the principles of approximation-transforming, pan-equivalence theorems, supply-demand analysis, thinking experiment, generalized gray systems, etc.
文摘Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within the realm of sports science and exercise medicine on the athletic gut microbiota.However,compared to other ergogenic aids and dietary supplements,probiotics present unique study challenges.The objectives of this systematic scoping review were to identify and characterize study methodologies of randomized controlled trials investigating supplementation with probiotics in athletes and physically active individuals.Methods:Four databases(MEDLINE,CINAHL,Cochrane CENTRAL,and Cochrane Database of Systematic Reviews)were searched for randomized controlled studies involving healthy athletes or physically active individuals.An intervention with probiotics and inclusion of a control and/or placebo group were essential.Only peer-reviewed articles in English were considered,and there were no date restrictions.Results were extracted and presented in tabular form to detail study protocols,characteristics,and outcomes.Bias in randomized controlled trials was determined with the RoB 2.0 tool.Results:A total of 45 studies were included in the review,with 35 using a parallel group design and 10 using a cross-over design.Approximately half the studies used a single probiotic and the other half a multi-strain preparation.The probiotic dose ranged from 2×10^(8)to 1×10^(11)colony forming units daily,and the length of intervention was between 7 and 150 days.Fewer than half the studies directly assessed gastrointestinal symptoms,gut permeability,or the gut microbiota.The sex ratio of participants was heavily weighted toward males,and only 3 studies exclusively investigated females.Low-level adverse events were reported in only 2 studies,although the methodology of reporting varied widely.The risk of bias was generally low,although details on randomization were lacking in some studies.Conclusion:There is a substantial body of research on the effects of prob iotic supplementation in healthy athletes and physically active individuals.Considerable heterogeneity in probiotic selection and dosage as well as outcome measures has made clinical and mechanistic interpretation challenging for both health care practitioners and researchers.Attention to issues of randomization of participants,treatments and interventions,selection of outcomes,demographics,and reporting of adverse events will facilitate more trustworthy interpretation of probiotic study results and inform evidence-based guidelines.
基金support of the Brazil-ian research agencies,the National Council for Scientific and Technological Development (CNPq)(Nos. 301355/2018-5 and 200198/2022-0)FAPERJ-CNE (No. E-26/202.711/2018)+1 种基金FAPERJ Nota 10 (No. E-26/200.357/2020)CAPES (Finance code 001 and 88881.310620/2018-01)。
文摘In a global dynamic analysis,the coexisting attractors and their basins are the main tools to understand the system behavior and safety.However,both basins and attractors can be drastically influenced by uncertainties.The aim of this work is to illustrate a methodology for the global dynamic analysis of nondeterministic dynamical systems with competing attractors.Accordingly,analytical and numerical tools for calculation of nondeterministic global structures,namely attractors and basins,are proposed.First,based on the definition of the Perron-Frobenius,Koopman and Foias linear operators,a global dynamic description through phase-space operators is presented for both deterministic and nondeterministic cases.In this context,the stochastic basins of attraction and attractors’distributions replace the usual basin and attractor concepts.Then,numerical implementation of these concepts is accomplished via an adaptative phase-space discretization strategy based on the classical Ulam method.Sample results of the methodology are presented for a canonical dynamical system.
文摘Some patterns of refined epitomes of pansystems methodology were revealed roles and the related of them in problem-solving, modeling, algorithm-generating and theory-constructing were introduced. An important application of pansystems methodology is to give some methods of constructing the typical pansymmetric-magic squares: 1. a method of recursively constructing magic squares of order n ( n greater than or equal to 5) ; 2. when magic squares of order m( m greater than or equal to 3) and magic squares of order n ( n greater than or equal to 3) are given of formula of obtaining magic squares of order nm; 3. when magic squares of order m ( m greater than or equal to 3) are given, a method of obtaining magic squares of order 2m.
文摘This paper deals with the Self-Increasing-Difficulty system (SIDIS) separated from general systems, with emphasis on the relevant methodology based on the Spiral Combining Propulsion Principle (SPIPRO principle in short). The system feature and its causative factors are analysed, and the implications and mechanism of the SPIPRO principle are discussed. Finally, the application possibilities of this methodology are illustrated with some examples.
基金funded by Toxicity Evaluation of Key Contaminants in Health Food by Cell-based Test Models and the Mechanism Analysis [2018YFC1602104]
文摘Objective This study optimizes three-dimensional(3D) culture conditions of HepG2 using response surface methodology(RSM) based on the VitroGel system to facilitate the cell model in vitro for liver tissues.Method HepG2 cell was 3D cultured on the VitroGel system.Cell viability was detected using Cell Counting Kit-8(CCK-8) assay of HepG2 lived cell numbers.The proliferation of HepG2 cell and clustering performance was measured via fluorescence staining test.Albumin concentration in the culture medium supernatant as an index of HepG2 cell biological function was measured with ELISA kit.Independent factor tests were conducted with three key factors:inoculated cell concentration,cultured time,and dilution degree of the hydrogel.The preliminary results of independent factor tests were used to determine the levels of factors for RSM.Result The selected optimal culture conditions are as follows:concentration of inoculated cells was4.44 × 10^(5)/mL,culture time was 4.86 days,and hydrogel dilution degree was 1:2.23.The result shows that under optimal conditions,the predicted optical density(OD) value of cell viability was 3.10 and measured 2.978 with a relative error of 3.94%.Conclusion This study serves as a reference for the 3D HepG2 culture and constructs liver tissues in vitro.Additionally,it provides the foundation for repeated dose high-throughput toxicity studies and other scientific research work.
基金Supported by Nuclear Safety Research Association and Tohoku University for Nuclear Researchers Exchange Program 2010National High Technology and Development Program ("863"Program)of China(No.2007AA041009)
文摘In this paper,the network reliability of an actual digital instrument and control system (DICS) network is analyzed by using GO-FLOW methodology (GFM).The evaluations of common-cause failure (CCF) and uncertainty are incorporated.Three significant CCF groups (real time servers,gateways,reactor protection system) and three typical time intervals (10 min,1 h,and 24 h) are selected in the analysis.It is concluded that the network contribution of CCF accounts for over 68% of the system failure probability.The result indicates that GFM is suitable for the network reliability analysis.
文摘This work investigates coag-flocculation optimization treatment of alum-brewery effluent system via response surface methodology (RSM). To minimize suspended and dissolved particles (SDP), experiments were carried out using nephelometric jar test and 23-factorial design with three star-points, six-center-points and two replications. A central composite design, which is the standard design of RSM, was used to evaluate the effects and interactions of three major factors (coagulation pH, coagulant dosage, settling time) on the treatment efficiency. Multivariable quadratic model developed for the response studied indicates the optimum conditions to be 9, 500mg/l and 20minutes for coagulation pH, coagulant dosage and settling time, respectively. At optimum, the SDP was reduced from 10831.490mg/l to 801.451mg/l, representing 92.601% removal efficiency. RSM has demonstrated to be appropriate approach for the optimization of the coag-flocculation process by statistical evaluation.