Combination of Neuro-Fuzzy Network Models with Biological Knowledge for Reconstructing Gene Regulatory Networks

Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly. In this paper, we propose a novel approach based on combining neuro-fu^zy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory nctworks＋ but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without lhctitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast, The results show that this approach can work effectively.

NEURO-FUZZY NETWORKS IN CAPP

The neuro-fuzzy network (NFN) is used to model the rules and experience of the process planner. NFN is to select the manufacturing operations sequences for the part features. A detailed description of the NFN system development is given. The rule structure utilizes sigmoid functions to fuzzify the inputs, multiplication to combine the if Part of the rules and summation to integrate the fired rules. Expert knowledge from previous process Plans is used in determinning the initial network structure and parameters of the membership functions. A back-propagation (BP) training algorithm was developed to fine tune the knowledge to company standards using the input-output data from executions of previous plans. The method is illustrated by an industrial example.

Modelling and Multi-Objective Optimal Control of Batch Processes Using Recurrent Neuro-fuzzy Networks

In this paper, the modelling and multi-objective optimal control of batch processes, using a recurrent neuro-fuzzy network, are presented. The recurrent neuro-fuzzy network, forms a ＂global＂ nonlinear long-range prediction model through the fuzzy conjunction of a number of ＂local＂ linear dynamic models. Network output is fed back to network input through one or more time delay units, which ensure that predictions from the recurrent neuro-fuzzy network are long-range. In building a recurrent neural network model, process knowledge is used initially to partition the processes non-linear characteristics into several local operating regions, and to aid in the initialisation of corresponding network weights. Process operational data is then used to train the network. Membership functions of the local regimes are identified, and local models are discovered via network training. Based on a recurrent neuro-fuzzy network model, a multi-objective optimal control policy can be obtained. The proposed technique is applied to a fed-batch reactor.

Study on fasART neuro-fuzzy networks for distinguishing the difficulty degree of top coal caving in steep seam

Distinguishing the difficulty degree of top coal caving was a precondition of the popularization and application of the roadway sub-level caving in steep seam. Because of complexity and uncertainty of the coal seam, the expression of influence factors was diffi-culty with exact data. According to the fuzzy and uncertainty of influence factors, triangular fuzzy membership functions were adopted to carry out the factors ambiguity, of which the factors not only have the consistency of semantic meaning, but also dissolve sufficiently expert knowledge. Based on the properties and structures of fasART fuzzy neural net-works of fuzzy logic system and practical needs, a simplified fasART model was put for-ward, stability and reliability of the network were improved, the deficiency of learning sam-ples and uncertainty of the factors were better treated. The method is of effective and practical value was identified by experiments.

Application of virtual reality technology improves the functionality of brain networks in individuals experiencing pain

Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and body.Recently,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)technology.VR has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been established.The precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be elucidated.However,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain networks.The salience network is diminished,while the default mode network is enhanced.Additionally,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and anxiety.Further research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.

Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

A chemical-reaction-optimization-based neuro-fuzzy hybrid network for stock closing price prediction

Accurate prediction of stock market behavior is a challenging issue for financial forecasting.Artificial neural networks,such as multilayer perceptron have been established as better approximation and classification models for this domain.This study proposes a chemical reaction optimization(CRO)based neuro-fuzzy network model for prediction of stock indices.The input vectors to the model are fuzzified by applying a Gaussian membership function,and each input is associated with a degree of membership to different classes.A multilayer perceptron with one hidden layer is used as the base model and CRO is used to the optimal weights and biases of this model.CRO was chosen because it requires fewer control parameters and has a faster convergence rate.Five statistical parameters are used to evaluate the performance of the model,and the model is validated by forecasting the daily closing indices for five major stock markets.The performance of the proposed model is compared with four state-of-art models that are trained similarly and was found to be superior.We conducted the Deibold-Mariano test to check the statistical significance of the proposed model,and it was found to be significant.This model can be used as a promising tool for financial forecasting.

Data Augmentation and Deep Neuro-fuzzy Network for Student Performance Prediction with MapReduce Framework

The main aim of an educational institute is to offer high-quality education to students. The system to achieve better quality in the educational system is to find the knowledge from educational data and to discover the attributes that manipulate the performance of students. Student performance prediction is a major issue in education and training, specifically in the educational data mining system. This research presents the student performance prediction approach with the MapReduce framework based on the proposed fractional competitive multi-verse optimization-based deep neuro-fuzzy network. The proposed fractional competitive multi-verse optimization-based deep neuro-fuzzy network is derived by integrating fractional calculus with competitive multi-verse optimization. The MapReduce framework is designed with the mapper and the reducer phase to perform the student performance prediction mechanism with the deep learning classifier. The input data is partitioned at the mapper phase to perform the data transformation process, and thereby the features are selected using the distance measure. The selected unique features are employed for the data segmentation process, and thereafter the prediction strategy is accomplished at the reducer phase by the deep neuro-fuzzy network classifier. The proposed method obtained the performance in terms of mean square error, root mean square error and mean absolute error with the values of 0.338 3, 0.581 7, and 0.391 5, respectively.

Intelligent non-linear modelling of an industrial winding process using recurrent local linear neuro-fuzzy networks

This study deals with the neuro-fuzzy (NF) modelling of a real industrial winding process in which the acquired NF model can be exploited to improve control performance and achieve a robust fault-tolerant system. A new simulator model is proposed for a winding process using non-linear identification based on a recurrent local linear neuro-fuzzy (RLLNF) network trained by local linear model tree (LOLIMOT), which is an incremental tree-based learning algorithm. The proposed NF models are compared with other known intelligent identifiers, namely multilayer perceptron (MLP) and radial basis function (RBF). Comparison of our proposed non-linear models and associated models obtained through the least square error (LSE) technique (the optimal modelling method for linear systems) confirms that the winding process is a non-linear system. Experimental results show the effectiveness of our proposed NF modelling approach.

Automatic Heart Disease Diagnosis System Based on Artificial Neural Network (ANN) and Adaptive Neuro-Fuzzy Inference Systems (ANFIS) Approaches

This paper aims to design and implement an automatic heart disease diagnosis system using?MATLAB. The Cleveland data set for heart diseases was used as the main database for training and testing the developed system. In order to train and test the Cleveland data set, two systems were developed. The first system is based on the Multilayer Perceptron (MLP) structure on the Artificial Neural Network (ANN), whereas the second system is based on the Adaptive Neuro-Fuzzy Inference Systems (ANFIS) approach. Each system has two main modules, namely, training and testing,?where 80% and 20% of the Cleveland data set were randomly selected for training and testing?purposes respectively. Each system also has an additional module known as case-based module,?where the user has to input values for 13 required attributes as specified by the Cleveland data set,?in order to test the status of the patient whether heart disease is present or absent from that particular patient. In addition, the effects of different values for important parameters were investigated in the ANN-based and Neuro-Fuzzy-based systems in order to select the best parameters that obtain the highest performance. Based on the experimental work, it is clear that the Neuro-Fuzzy system outperforms the ANN system using the training data set, where the accuracy for each system was 100% and 90.74%, respectively. However, using the testing data set, it is clear that the ANN system outperforms the Neuro-Fuzzy system, where the best accuracy for each system was 87.04% and 75.93%, respectively.

Column breakthrough studies for the removal and recovery of phosphate by lime-iron sludge:Modeling and optimization using artificial neural network and adaptive neuro-fuzzy inference system

Increases in the treatment of water to meet the growing water demand ultimately result in unmanageable quantities of residuals,the handling,and disposal of which is a major environmental issue.Consequently,research into beneficial reuse of water treatment residuals continues unabated.This study investigated the applicability of lime-iron sludge for phosphate adsorption by fixed-bed column adsorption.Laboratory-scale experiments were conducted at varying flow rates and bed depths.Fundamental and empirical models(Thomas,Yan,Bohart-Adams,Yoon-Nelson,and Wolboroska)as well as artificial intelligence techniques(Artificial neural network(ANN)and Adaptive neuro-fuzzy inference system(ANFIS))were used to simulate experimental breakthrough curves and predict column dynamics.Increase in flow rate resulted in reduced adsorption capacity.However,adsorption capacity was not affected by bed depth.ANN was superior in predicting breakthrough curves and predicted breakthrough times with high accuracy(R^2>0.9962).Na OH(0.5 mol·L^-1)was successfully used to regenerate the adsorption bed.After nine cyclic adsorption/desorption runs,only a marginal decrease in adsorption and desorption efficiencies of 10%and 8%respectively was observed.The same regenerate Na OH solution was reused for all desorption cycles.After nine cycles the eluent desorbed a total of 1550 mg phosphate exhibiting potential for further reuse.

Pluggable multitask diffractive neural networks based on cascaded metasurfaces

Optical neural networks have significant advantages in terms of power consumption,parallelism,and high computing speed,which has intrigued extensive attention in both academic and engineering communities.It has been considered as one of the powerful tools in promoting the fields of imaging processing and object recognition.However,the existing optical system architecture cannot be reconstructed to the realization of multi-functional artificial intelligence systems simultaneously.To push the development of this issue,we propose the pluggable diffractive neural networks(P-DNN),a general paradigm resorting to the cascaded metasurfaces,which can be applied to recognize various tasks by switching internal plug-ins.As the proof-of-principle,the recognition functions of six types of handwritten digits and six types of fashions are numerical simulated and experimental demonstrated at near-infrared regimes.Encouragingly,the proposed paradigm not only improves the flexibility of the optical neural networks but paves the new route for achieving high-speed,low-power and versatile artificial intelligence systems.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).

Social-ecological perspective on the suicidal behaviour factors of early adolescents in China:a network analysis

Background In early adolescence,youth are highly prone to suicidal behaviours.Identifying modifiable risk factors during this critical phase is a priority to inform effective suicide prevention strategies.Aims To explore the risk and protective factors of suicidal behaviours(ie,suicidal ideation,plans and attempts)in early adolescence in China using a social-ecological perspective.Methods Using data from the cross-sectional project‘Healthy and Risky Behaviours Among Middle School Students in Anhui Province,China',stratified random cluster sampling was used to select 5724 middle school students who had completed self-report questionnaires in November 2020.Network analysis was employed to examine the correlates of suicidal ideation,plans and attempts at four levels,namely individual(sex,academic performance,serious physical llness/disability,history of self-harm,depression,impulsivity,sleep problems,resilience),family(family economic status,relationship with mother,relationship with father,family violence,childhood abuse,parental mental illness),school(relationship with teachers,relationship with classmates,school-bullying victimisation and perpetration)and social(social support,satisfaction with society).Results In total,37.9%,19.0%and 5.5%of the students reported suicidal ideation,plans and attempts in the past 6 months,respectively.The estimated network revealed that suicidal ideation,plans and attempts were collectively associated with a history of self-harm,sleep problems,childhood abuse,school bullying and victimisation.Centrality analysis indicated that the most influential nodes in the network were history of self-harm and childhood abuse.Notably,the network also showed unique correlates of suicidal ideation(sex,weight=0.60;impulsivity,weight=0.24;family violence,weight=0.17;relationship with teachers,weight=-0.03;school-bullying perpetration,weight=0.22),suicidal plans(social support,weight=-0.15)and suicidal attempts(relationship with mother,weight=-0.10;parental mental llness,weight=0.61).Conclusions This study identified the correlates of suicidal ideation,plans and attempts,and provided practical implications for suicide prevention for young adolescents in China.Firstly,this study highlighted the importance of joint interventions across multiple departments.Secondly,the common risk factors of suicidal ideation,plans and attempts were elucidated.Thirdly,this study proposed target interventions to address the unique influencing factors of suicidal ideation,plans and attempts.

Comparison between Neural Network and Adaptive Neuro-Fuzzy Inference System for Forecasting Chaotic Traffic Volumes

This paper applies both the neural network and adaptive neuro-fuzzy inference system for forecasting short-term chaotic traffic volumes and compares the results. The architecture of the neural network consists of the input vector, one hidden layer and output layer. Bayesian regularization is employed to obtain the effective number of neurons in the hidden layer. The input variables and target of the adaptive neuro-fuzzy inference system are the same as those of the neural network. The data clustering technique is used to group data points so that the membership functions will be more tailored to the input data, which in turn greatly reduces the number of fuzzy rules. Numerical results indicate that these two models have almost the same accuracy, while the adaptive neuro-fuzzy inference system takes more time to train. It is also shown that although the effective number of neurons in the hidden layer is less than half the number of the input elements, the neural network can have satisfactory performance.

Image super‐resolution via dynamic network

Convolutional neural networks depend on deep network architectures to extract accurate information for image super‐resolution.However,obtained information of these con-volutional neural networks cannot completely express predicted high‐quality images for complex scenes.A dynamic network for image super‐resolution(DSRNet)is presented,which contains a residual enhancement block,wide enhancement block,feature refine-ment block and construction block.The residual enhancement block is composed of a residual enhanced architecture to facilitate hierarchical features for image super‐resolution.To enhance robustness of obtained super‐resolution model for complex scenes,a wide enhancement block achieves a dynamic architecture to learn more robust information to enhance applicability of an obtained super‐resolution model for varying scenes.To prevent interference of components in a wide enhancement block,a refine-ment block utilises a stacked architecture to accurately learn obtained features.Also,a residual learning operation is embedded in the refinement block to prevent long‐term dependency problem.Finally,a construction block is responsible for reconstructing high‐quality images.Designed heterogeneous architecture can not only facilitate richer structural information,but also be lightweight,which is suitable for mobile digital devices.Experimental results show that our method is more competitive in terms of performance,recovering time of image super‐resolution and complexity.The code of DSRNet can be obtained at https://github.com/hellloxiaotian/DSRNet.

Mapping Network-Coordinated Stacked Gated Recurrent Units for Turbulence Prediction

Accurately predicting fluid forces acting on the sur-face of a structure is crucial in engineering design.However,this task becomes particularly challenging in turbulent flow,due to the complex and irregular changes in the flow field.In this study,we propose a novel deep learning method,named mapping net-work-coordinated stacked gated recurrent units(MSU),for pre-dicting pressure on a circular cylinder from velocity data.Specifi-cally,our coordinated learning strategy is designed to extract the most critical velocity point for prediction,a process that has not been explored before.In our experiments,MSU extracts one point from a velocity field containing 121 points and utilizes this point to accurately predict 100 pressure points on the cylinder.This method significantly reduces the workload of data measure-ment in practical engineering applications.Our experimental results demonstrate that MSU predictions are highly similar to the real turbulent data in both spatio-temporal and individual aspects.Furthermore,the comparison results show that MSU predicts more precise results,even outperforming models that use all velocity field points.Compared with state-of-the-art methods,MSU has an average improvement of more than 45%in various indicators such as root mean square error(RMSE).Through comprehensive and authoritative physical verification,we estab-lished that MSU’s prediction results closely align with pressure field data obtained in real turbulence fields.This confirmation underscores the considerable potential of MSU for practical applications in real engineering scenarios.The code is available at https://github.com/zhangzm0128/MSU.

Applying an Improved Dung Beetle Optimizer Algorithm to Network Traffic Identification

Network traffic identification is critical for maintaining network security and further meeting various demands of network applications.However,network traffic data typically possesses high dimensionality and complexity,leading to practical problems in traffic identification data analytics.Since the original Dung Beetle Optimizer(DBO)algorithm,Grey Wolf Optimization(GWO)algorithm,Whale Optimization Algorithm(WOA),and Particle Swarm Optimization(PSO)algorithm have the shortcomings of slow convergence and easily fall into the local optimal solution,an Improved Dung Beetle Optimizer(IDBO)algorithm is proposed for network traffic identification.Firstly,the Sobol sequence is utilized to initialize the dung beetle population,laying the foundation for finding the global optimal solution.Next,an integration of levy flight and golden sine strategy is suggested to give dung beetles a greater probability of exploring unvisited areas,escaping from the local optimal solution,and converging more effectively towards a global optimal solution.Finally,an adaptive weight factor is utilized to enhance the search capabilities of the original DBO algorithm and accelerate convergence.With the improvements above,the proposed IDBO algorithm is then applied to traffic identification data analytics and feature selection,as so to find the optimal subset for K-Nearest Neighbor(KNN)classification.The simulation experiments use the CICIDS2017 dataset to verify the effectiveness of the proposed IDBO algorithm and compare it with the original DBO,GWO,WOA,and PSO algorithms.The experimental results show that,compared with other algorithms,the accuracy and recall are improved by 1.53%and 0.88%in binary classification,and the Distributed Denial of Service(DDoS)class identification is the most effective in multi-classification,with an improvement of 5.80%and 0.33%for accuracy and recall,respectively.Therefore,the proposed IDBO algorithm is effective in increasing the efficiency of traffic identification and solving the problem of the original DBO algorithm that converges slowly and falls into the local optimal solution when dealing with high-dimensional data analytics and feature selection for network traffic identification.