The potential of gene therapies for spinal cord injury repair:a systematic review and meta-analysis of pre-clinical studies

Currently,there is no cure for traumatic spinal co rd injury but one therapeutic approach showing promise is gene therapy.In this systematic review and meta-analysis,we aim to assess the efficacy of gene therapies in pre-clinical models of spinal cord injury and the risk of bias.In this metaanalysis,registe red at PROSPERO(Registration ID:CRD42020185008),we identified relevant controlled in vivo studies published in English by searching the PubMed,Web of Science,and Embase databases.No restrictions of the year of publication were applied and the last literature search was conducted on August 3,2020.We then conducted a random-effects meta-analysis using the restricted maximum likelihood estimator.A total of 71 studies met our inclusion crite ria and were included in the systematic review.Our results showed that overall,gene therapies were associated with improvements in locomotor score(standardized mean difference[SMD]:2.07,95%confidence interval[CI]:1.68-2.47,Tau^(2)=2.13,I^(2)=83.6%)and axonal regrowth(SMD:2.78,95%CI:1.92-3.65,Tau^(2)=4.13,I^(2)=85.5%).There was significant asymmetry in the funnel plots of both outcome measures indicating the presence of publication bias.We used a modified CAMARADES(Collaborative Approach to M eta-Analysis and Review of Animal Data in Experimental Studies)checklist to assess the risk of bias,finding that the median score was 4(IQR:3-5).In particula r,reports of allocation concealment and sample size calculations were lacking.In conclusion,gene therapies are showing promise as therapies for spinal co rd injury repair,but there is no consensus on which gene or genes should be targeted.

CRISPR/Cas9 systems:Delivery technologies and biomedical applications

The emergence of the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome-editing system has brought about a significant revolution in the realm of managing human diseases,establishing animal models,and so on.To fully harness the potential of this potent gene-editing tool,ensuring efficient and secure delivery to the target site is paramount.Consequently,developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research.In this review,we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system.We also provide an indepth analysis of physical,viral vector,and non-viral vector delivery strategies,including plasmid-,mRNA-and protein-based approach.In addition,we illustrate the biomedical applications of the CRISPR/Cas9 system.This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system,while also delineating future directions and prospects that could inspire innovative delivery strategies.This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.

Insights on drug and gene delivery systems in liver fibrosis

Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.

A new hybrid approach to assessing soil quality using neutrosophic fuzzy-AHP and support vector machine algorithm in sub-humid ecosystem

Soil quality determination and estimation is an important issue not only for terrestrial ecosystems but also for sustainable management of soils.In this study,soil quality was determined by linear and nonlinear standard scoring function methods integrated with a neutrosophic fuzzy analytic hierarchy process in the micro catchment.In addition,soil quality values were estimated using a support vector machine(SVM)in machine learning algorithms.In order to generate spatial distribution maps of soil quality indice values,different interpolation methods were evaluated to detect the most suitable semivariogram model.While the soil quality index values obtained by the linear method were determined between 0.458-0.717,the soil quality index with the nonlinear method showed variability at the levels of 0.433-0.651.There was no statistical difference between the two methods,and they were determined to be similar.In the estimation of soil quality with SVM,the normalized root means square error(NRMSE)values obtained in the linear and nonlinear method estimation were determined as 0.057 and 0.047,respectively.The spherical model of simple kriging was determined as the interpolation method with the lowest RMSE value in the actual and predicted values of the linear method while,in the nonlinear method,the lowest error in the distribution maps was determined with exponential of the simple kriging.

DNA Computing with Water Strider Based Vector Quantization for Data Storage Systems

The exponential growth of data necessitates an effective data storage scheme,which helps to effectively manage the large quantity of data.To accomplish this,Deoxyribonucleic Acid(DNA)digital data storage process can be employed,which encodes and decodes binary data to and from synthesized strands of DNA.Vector quantization(VQ)is a commonly employed scheme for image compression and the optimal codebook generation is an effective process to reach maximum compression efficiency.This article introduces a newDNAComputingwithWater StriderAlgorithm based Vector Quantization(DNAC-WSAVQ)technique for Data Storage Systems.The proposed DNAC-WSAVQ technique enables encoding data using DNA computing and then compresses it for effective data storage.Besides,the DNAC-WSAVQ model initially performsDNA encoding on the input images to generate a binary encoded form.In addition,aWater Strider algorithm with Linde-Buzo-Gray(WSA-LBG)model is applied for the compression process and thereby storage area can be considerably minimized.In order to generate optimal codebook for LBG,the WSA is applied to it.The performance validation of the DNAC-WSAVQ model is carried out and the results are inspected under several measures.The comparative study highlighted the improved outcomes of the DNAC-WSAVQ model over the existing methods.

Support vector regression-based operational effectiveness evaluation approach to reconnaissance satellite system

As one of the most important part of weapon system of systems(WSoS),quantitative evaluation of reconnaissance satellite system(RSS)is indispensable during its construction and application.Aiming at the problem of nonlinear effectiveness evaluation under small sample conditions,we propose an evaluation method based on support vector regression(SVR)to effectively address the defects of traditional methods.Considering the performance of SVR is influenced by the penalty factor,kernel type,and other parameters deeply,the improved grey wolf optimizer(IGWO)is employed for parameter optimization.In the proposed IGWO algorithm,the opposition-based learning strategy is adopted to increase the probability of avoiding the local optima,the mutation operator is used to escape from premature convergence and differential convergence factors are applied to increase the rate of convergence.Numerical experiments of 14 test functions validate the applicability of IGWO algorithm dealing with global optimization.The index system and evaluation method are constructed based on the characteristics of RSS.To validate the proposed IGWO-SVR evaluation method,eight benchmark data sets and combat simulation are employed to estimate the evaluation accuracy,convergence performance and computational complexity.According to the experimental results,the proposed method outperforms several prediction based evaluation methods,verifies the superiority and effectiveness in RSS operational effectiveness evaluation.

An Effective Diagnosis System for Brain Tumor Detection and Classification

A brain tumor is an excessive development of abnormal and uncontrolled cells in the brain.This growth is considered deadly since it may cause death.The brain controls numerous functions,such as memory,vision,and emotions.Due to the location,size,and shape of these tumors,their detection is a challenging and complex task.Several efforts have been conducted toward improved detection and yielded promising results and outcomes.However,the accuracy should be higher than what has been reached.This paper presents a method to detect brain tumors with high accuracy.The method works using an image segmentation technique and a classifier in MATLAB.The utilized classifier is a SupportVector Machine(SVM).DiscreteWavelet Transform(DWT)and Principal Component Analysis(PCA)are also involved.A dataset from the Kaggle website is used to test the developed approach.The obtained results reached nearly 99.2%of accuracy.The paper provides a confusion matrix of applying the proposed approach to testing images and a comparative evaluation between the developed method and some works in the literature.This evaluation shows that the presented system outperforms other approaches regarding the accuracy,precision,and recall.This research discovered that the developed method is extremely useful in detecting brain tumors,given the high accuracy,precision,and recall results.The proposed system directs us to believe that bringing this kind of technology to physicians diagnosing brain tumors is crucial.

Skin Lesion Classification System Using Shearlets

The main cause of skin cancer is the ultraviolet radiation of the sun.It spreads quickly to other body parts.Thus,early diagnosis is required to decrease the mortality rate due to skin cancer.In this study,an automatic system for Skin Lesion Classification(SLC)using Non-Subsampled Shearlet Transform(NSST)based energy features and Support Vector Machine(SVM)classifier is proposed.Atfirst,the NSST is used for the decomposition of input skin lesion images with different directions like 2,4,8 and 16.From the NSST’s sub-bands,energy fea-tures are extracted and stored in the feature database for training.SVM classifier is used for the classification of skin lesion images.The dermoscopic skin images are obtained from PH^(2) database which comprises of 200 dermoscopic color images with melanocytic lesions.The performances of the SLC system are evaluated using the confusion matrix and Receiver Operating Characteristic(ROC)curves.The SLC system achieves 96%classification accuracy using NSST’s energy fea-tures obtained from 3^(rd) level with 8-directions.

A Highly Accurate Dysphonia Detection System Using Linear Discriminant Analysis

The recognition of pathological voice is considered a difficult task for speech analysis.Moreover,otolaryngologists needed to rely on oral communication with patients to discover traces of voice pathologies like dysphonia that are caused by voice alteration of vocal folds and their accuracy is between 60%–70%.To enhance detection accuracy and reduce processing speed of dysphonia detection,a novel approach is proposed in this paper.We have leveraged Linear Discriminant Analysis(LDA)to train multiple Machine Learning(ML)models for dysphonia detection.Several ML models are utilized like Support Vector Machine(SVM),Logistic Regression,and K-nearest neighbor(K-NN)to predict the voice pathologies based on features like Mel-Frequency Cepstral Coefficients(MFCC),Fundamental Frequency(F0),Shimmer(%),Jitter(%),and Harmonic to Noise Ratio(HNR).The experiments were performed using Saarbrucken Voice Data-base(SVD)and a privately collected dataset.The K-fold cross-validation approach was incorporated to increase the robustness and stability of the ML models.According to the experimental results,our proposed approach has a 70%increase in processing speed over Principal Component Analysis(PCA)and performs remarkably well with a recognition accuracy of 95.24%on the SVD dataset surpassing the previous best accuracy of 82.37%.In the case of the private dataset,our proposed method achieved an accuracy rate of 93.37%.It can be an effective non-invasive method to detect dysphonia.

A semantic vector map-based approach for aircraft positioning in GNSS/GPS denied large-scale environment

Accurate positioning is one of the essential requirements for numerous applications of remote sensing data,especially in the event of a noisy or unreliable satellite signal.Toward this end,we present a novel framework for aircraft geo-localization in a large range that only requires a downward-facing monocular camera,an altimeter,a compass,and an open-source Vector Map(VMAP).The algorithm combines the matching and particle filter methods.Shape vector and correlation between two building contour vectors are defined,and a coarse-to-fine building vector matching(CFBVM)method is proposed in the matching stage,for which the original matching results are described by the Gaussian mixture model(GMM).Subsequently,an improved resampling strategy is designed to reduce computing expenses with a huge number of initial particles,and a credibility indicator is designed to avoid location mistakes in the particle filter stage.An experimental evaluation of the approach based on flight data is provided.On a flight at a height of 0.2 km over a flight distance of 2 km,the aircraft is geo-localized in a reference map of 11,025 km~2using 0.09 km~2aerial images without any prior information.The absolute localization error is less than 10 m.

Biotin-modified Galactosylated Chitosan-gene Carrier in Hepatoma Cells Targeting Delivery

Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1.At this N/P ratio,the transfection efficiency in the hepatoma cells was the highest with a slow release effect.Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation,and can target the transfection into hepatoma cells by combination with galactose and biotin receptors.The transfection rate was inhibited by the competition of galactose and biotin.Bio-GC nanomaterials were imported into cells’cytoplasm by their receptors,followed by the imported exogenous gene transfected into the cells.Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice,by carrying the gene through the blood to the hepatoma tissue.Taken together,bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation,improving the rate of transfection in hepatoma cells,and transporting the gene into the cytoplasm in vitro and in vivo.Therefore,they are efficient hepatoma-targeting gene carriers.

An Initial Perturbation Method for the Multiscale Singular Vector in Global Ensemble Prediction

Ensemble prediction is widely used to represent the uncertainty of single deterministic Numerical Weather Prediction(NWP) caused by errors in initial conditions(ICs). The traditional Singular Vector(SV) initial perturbation method tends only to capture synoptic scale initial uncertainty rather than mesoscale uncertainty in global ensemble prediction. To address this issue, a multiscale SV initial perturbation method based on the China Meteorological Administration Global Ensemble Prediction System(CMA-GEPS) is proposed to quantify multiscale initial uncertainty. The multiscale SV initial perturbation approach entails calculating multiscale SVs at different resolutions with multiple linearized physical processes to capture fast-growing perturbations from mesoscale to synoptic scale in target areas and combining these SVs by using a Gaussian sampling method with amplitude coefficients to generate initial perturbations. Following that, the energy norm,energy spectrum, and structure of multiscale SVs and their impact on GEPS are analyzed based on a batch experiment in different seasons. The results show that the multiscale SV initial perturbations can possess more energy and capture more mesoscale uncertainties than the traditional single-SV method. Meanwhile, multiscale SV initial perturbations can reflect the strongest dynamical instability in target areas. Their performances in global ensemble prediction when compared to single-scale SVs are shown to(i) improve the relationship between the ensemble spread and the root-mean-square error and(ii) provide a better probability forecast skill for atmospheric circulation during the late forecast period and for short-to medium-range precipitation. This study provides scientific evidence and application foundations for the design and development of a multiscale SV initial perturbation method for the GEPS.

Forward modelling of the Cotton-Mouton effect polarimetry on EAST tokamak

Measurement of plasma electron density by far-infrared laser polarimetry has become a routine and indispensable tool in magnetic confinement fusion research.This article presents the design of a Cotton-Mouton polarimeter interferometer,which provides a reliable density measurement without fringe jumps.Cotton-Mouton effect on Experimental Advanced Superconducting Tokamak(EAST)is studied by Stokes equation with three parameters(s_(1),s_(2),s_(3)).It demonstrates that under the condition of a small Cotton-Mouton effect,parameter s_(2)contains information about Cotton-Mouton effect which is proportional to the line-integrated density.For a typical EAST plasma,the magnitude of Cotton-Mouton effects is less than 2πfor laser wavelength of 432μm.Refractive effect due to density gradient is calculated to be negligible.Time modulation of Stokes parameters(s_(2),s_(3))provides heterodyne measurement.Due to the instabilities arising from laser oscillation and beam refraction in plasmas,it is necessary for the system to be insensitive to variations in the amplitude of the detection signal.Furthermore,it is shown that non-equal amplitude of X-mode and O-mode within a certain range only affects the DC offset of Stokes parameters(s_(2),s_(3))but does not greatly influence the phase measurements of Cotton-Mouton effects.

Compression and stretching of ring vortex in a bulk nonlinear medium

We explore the nonlinear gain coupled Schrödinger system through the utilization of the variables separation method and ansatz technique.By employing these approaches,we generate hierarchies of explicit dissipative vector vortices(DVVs)that possess diverse vorticity values.Numerous fundamental characteristics of the DVVs are examined,encompassing amplitude profiles,energy fluxes,parameter effects,as well as linear and dynamic stability.

Diffraction deep neural network-based classification for vector vortex beams

The vector vortex beam(VVB)has attracted significant attention due to its intrinsic diversity of information and has found great applications in both classical and quantum communications.However,a VVB is unavoidably affected by atmospheric turbulence(AT)when it propagates through the free-space optical communication environment,which results in detection errors at the receiver.In this paper,we propose a VVB classification scheme to detect VVBs with continuously changing polarization states under AT,where a diffractive deep neural network(DDNN)is designed and trained to classify the intensity distribution of the input distorted VVBs,and the horizontal direction of polarization of the input distorted beam is adopted as the feature for the classification through the DDNN.The numerical simulations and experimental results demonstrate that the proposed scheme has high accuracy in classification tasks.The energy distribution percentage remains above 95%from weak to medium AT,and the classification accuracy can remain above 95%for various strengths of turbulence.It has a faster convergence and better accuracy than that based on a convolutional neural network.

Improved Twin Support Vector Machine Algorithm and Applications in Classification Problems

The distribution of data has a significant impact on the results of classification.When the distribution of one class is insignificant compared to the distribution of another class,data imbalance occurs.This will result in rising outlier values and noise.Therefore,the speed and performance of classification could be greatly affected.Given the above problems,this paper starts with the motivation and mathematical representing of classification,puts forward a new classification method based on the relationship between different classification formulations.Combined with the vector characteristics of the actual problem and the choice of matrix characteristics,we firstly analyze the orderly regression to introduce slack variables to solve the constraint problem of the lone point.Then we introduce the fuzzy factors to solve the problem of the gap between the isolated points on the basis of the support vector machine.We introduce the cost control to solve the problem of sample skew.Finally,based on the bi-boundary support vector machine,a twostep weight setting twin classifier is constructed.This can help to identify multitasks with feature-selected patterns without the need for additional optimizers,which solves the problem of large-scale classification that can’t deal effectively with the very low category distribution gap.

A Novel Prescribed-Performance Path-Following Problem for Non-Holonomic Vehicles

The issue of achieving prescribed-performance path following in robotics is addressed in this paper,where the aim is to ensure that a desired path within a specified region is accu-rately converged to by the controlled vehicle.In this context,a novel form of the prescribed performance guiding vector field is introduced,accompanied by a prescribed-time sliding mode con-trol approach.Furthermore,the interdependence among the pre-scribed parameters is discussed.To validate the effectiveness of the proposed method,numerical simulations are presented to demonstrate the efficacy of the approach.

Machine learning-assisted efficient design of Cu-based shape memory alloy with specific phase transition temperature

The martensitic transformation temperature is the basis for the application of shape memory alloys(SMAs),and the ability to quickly and accurately predict the transformation temperature of SMAs has very important practical significance.In this work,machine learning(ML)methods were utilized to accelerate the search for shape memory alloys with targeted properties(phase transition temperature).A group of component data was selected to design shape memory alloys using reverse design method from numerous unexplored data.Component modeling and feature modeling were used to predict the phase transition temperature of the shape memory alloys.The experimental results of the shape memory alloys were obtained to verify the effectiveness of the support vector regression(SVR)model.The results show that the machine learning model can obtain target materials more efficiently and pertinently,and realize the accurate and rapid design of shape memory alloys with specific target phase transition temperature.On this basis,the relationship between phase transition temperature and material descriptors is analyzed,and it is proved that the key factors affecting the phase transition temperature of shape memory alloys are based on the strength of the bond energy between atoms.This work provides new ideas for the controllable design and performance optimization of Cu-based shape memory alloys.

Comparison of debris flow susceptibility assessment methods:support vector machine,particle swarm optimization,and feature selection techniques

The selection of important factors in machine learning-based susceptibility assessments is crucial to obtain reliable susceptibility results.In this study,metaheuristic optimization and feature selection techniques were applied to identify the most important input parameters for mapping debris flow susceptibility in the southern mountain area of Chengde City in Hebei Province,China,by using machine learning algorithms.In total,133 historical debris flow records and 16 related factors were selected.The support vector machine(SVM)was first used as the base classifier,and then a hybrid model was introduced by a two-step process.First,the particle swarm optimization(PSO)algorithm was employed to select the SVM model hyperparameters.Second,two feature selection algorithms,namely principal component analysis(PCA)and PSO,were integrated into the PSO-based SVM model,which generated the PCA-PSO-SVM and FS-PSO-SVM models,respectively.Three statistical metrics(accuracy,recall,and specificity)and the area under the receiver operating characteristic curve(AUC)were employed to evaluate and validate the performance of the models.The results indicated that the feature selection-based models exhibited the best performance,followed by the PSO-based SVM and SVM models.Moreover,the performance of the FS-PSO-SVM model was better than that of the PCA-PSO-SVM model,showing the highest AUC,accuracy,recall,and specificity values in both the training and testing processes.It was found that the selection of optimal features is crucial to improving the reliability of debris flow susceptibility assessment results.Moreover,the PSO algorithm was found to be not only an effective tool for hyperparameter optimization,but also a useful feature selection algorithm to improve prediction accuracies of debris flow susceptibility by using machine learning algorithms.The high and very high debris flow susceptibility zone appropriately covers 38.01%of the study area,where debris flow may occur under intensive human activities and heavy rainfall events.

Differentially Private Support Vector Machines with Knowledge Aggregation

With the widespread data collection and processing,privacy-preserving machine learning has become increasingly important in addressing privacy risks related to individuals.Support vector machine(SVM)is one of the most elementary learning models of machine learning.Privacy issues surrounding SVM classifier training have attracted increasing attention.In this paper,we investigate Differential Privacy-compliant Federated Machine Learning with Dimensionality Reduction,called FedDPDR-DPML,which greatly improves data utility while providing strong privacy guarantees.Considering in distributed learning scenarios,multiple participants usually hold unbalanced or small amounts of data.Therefore,FedDPDR-DPML enables multiple participants to collaboratively learn a global model based on weighted model averaging and knowledge aggregation and then the server distributes the global model to each participant to improve local data utility.Aiming at high-dimensional data,we adopt differential privacy in both the principal component analysis(PCA)-based dimensionality reduction phase and SVM classifiers training phase,which improves model accuracy while achieving strict differential privacy protection.Besides,we train Differential privacy(DP)-compliant SVM classifiers by adding noise to the objective function itself,thus leading to better data utility.Extensive experiments on three high-dimensional datasets demonstrate that FedDPDR-DPML can achieve high accuracy while ensuring strong privacy protection.