Construction and Identification of the Helper Plasmids for Reverse Genetic System of Rabies Virus Street Strain

To obtain the helper plasmids for a reverse genetics system of rabies virus, the cDNAs of the complete open reading frames of the N, P, G, and L genes of rabies street virus stain HN10 were each cloned into expression vector pVAX1, These four plasmids were identified by restriction enzyme digestion and gene sequencing. The plasmid encoding the N protein was selected to determine the expression effect of these plasmids in NA cells. The results showed that the helper plasmids for a reverse genetics system of rabies street virus strain HN10 had been successfully constructed.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Fuzzy inference system using genetic algorithm and pattern search for predicting roof fall rate in underground coal mines

One of the most dangerous safety hazard in underground coal mines is roof falls during retreat mining.Roof falls may cause life-threatening and non-fatal injuries to miners and impede mining and transportation operations.As a result,a reliable roof fall prediction model is essential to tackle such challenges.Different parameters that substantially impact roof falls are ill-defined and intangible,making this an uncertain and challenging research issue.The National Institute for Occupational Safety and Health assembled a national database of roof performance from 37 coal mines to explore the factors contributing to roof falls.Data acquired for 37 mines is limited due to several restrictions,which increased the likelihood of incompleteness.Fuzzy logic is a technique for coping with ambiguity,incompleteness,and uncertainty.Therefore,In this paper,the fuzzy inference method is presented,which employs a genetic algorithm to create fuzzy rules based on 109 records of roof fall data and pattern search to refine the membership functions of parameters.The performance of the deployed model is evaluated using statistical measures such as the Root-Mean-Square Error,Mean-Absolute-Error,and coefficient of determination(R_(2)).Based on these criteria,the suggested model outperforms the existing models to precisely predict roof fall rates using fewer fuzzy rules.

Characteristics and genetic mechanism of the Mesoproterozoic rift system,Ordos Basin,China

The Mesoproterozoic rifts are developed in the Ordos Basin located in the western margin of the North China Plate.Based on the latest 3D seismic data and previous research results,this study intends to discuss the zonal differential deformation characteristics and genetic mechanism of the Mesoproterozoic rifts in the Ordos Basin.NE-trending rifts are developed in the Mesoproterozoic in the south-central Ordos Basin,the main part of which are located near the western margin of the North China Plate.NNW-trending rifts are developed in the north of the basin,while NW-NNW rifts in the Mesoproterozoic in Hangjinqi area.The genetic mechanism of the Mesoproterozoic rifts is related to regional extensional stress field,plate boundary conditions and internal preexisting structures.The main extensional stress direction strikes NWW-SSE(120°)in the western margin of the North China Plate,based on the forward rift trend of the northern Mesoproterozoic.In Hangjinqi area,the reactivation of the existing NWtrending Wulansu fault and NW-NW-trending Daolao fault,results in dextral shear stress field.The boundary between the western margin of the North China Plate and its adjacent plates forms a nearly NS-trending preexisting basement tectonic belt,which intersects with the NWW-SSE(120°)extensional stress at an acute angle of 60°.Therefore,the western margin of the North China Plate is formed by oblique normal faults under oblique extension.Due to the long time span of Columbia Supercontinent breakup(1.8e1.6 Ga),the oblique rift in the south-central Ordos Basin is formed under the continuous oblique extension at the western margin of the North China Plate.

Comparative Study on Genetic Diversity of Beauveria bassiana in Different Forest Ecosystems

ISSR molecular marker technology was adopted to conduct comparison analysis on genetic diversity level and population genetic structure of Beauveria bassiana population in natural secondary forest （Langyashan national forest park） in Chuzhou City of Anhui Province and artificial pure pine forest （Magushan forest farm） in Xuancheng City of Anhui Province.Seven primers were selected to conduct PCR amplification on total 222 strains of B.bassiana in two populations,a total of 58 unique amplified loci were obtained through amplification,the number of polymorphic loci was 56,the percentage of polymorphic loci was 96.55%,Nei＇s genetic diversity was 0.299 3,Shannon information index was 0.459 3,genetic differentiation coefficient among populations （Gst） was 0.128 3,gene flow Nm=3.398 4;the gene flow between the two populations was small,genetic differentiation was relatively large,being 12.83%,this may be caused by human selective pressures and barrier of gene flow;the genetic variation level of B.bassiana populations in Langyashan was relatively high（PPL=96.55%,H=0.278 1,I= 0.429 9）;the genetic variation level of B.bassiana populations in Magushan was relatively low（PPL=93.10%,H=0.255 2,I= 0.382 5）.The genetic diversity of B.bassiana from the primary forest in Dabieshan was studied（PPL=81.00%,H=0.318 7,I= 0.478 2）,indicating that the genetic diversity of B.bassiana populations in Dabieshan with complex ecological environment was the highest,followed by the populations in natural secondary forest,and the genetic diversity in artificial pure pine forest was the lowest.Nei＇s genetic distance was adopted to construct the genetic relationship dendrogram of B.bassiana individuals collected from Langyashan and Magushan,from the cluster analysis of UPGMA,the strains from the same collection places clustered together.

Establishment of a Reverse Genetic System of Severe Fever with Thrombocytopenia Syndrome Virus Based on a C4 Strain

Severe fever with thrombocytopenia syndrome virus(SFTSV)is an emerging tick-borne bunyavirus that causes hemorrhagic fever-like disease(SFTS)in humans with a case fatality rate up to 30%.To date,the molecular biology involved in SFTSV infection remains obscure.There are seven major genotypes of SFTSV(C1-C4 and J1-J3)and previously a reverse genetic system was established on a C3 strain of SFTSV.Here,we reported successfully establishment of a reverse genetics system based on a SFTSV C4 strain.First,we obtained the 5’-and 3’-terminal untranslated region(UTR)sequences of the Large(L),Medium(M)and Small(S)segments of a laboratory-adapted SFTSV C4 strain through rapid amplification of cDNA ends analysis,and developed functional T7 polymerase-based L-,M-and S-segment minigenome assays.Then,fulllength cDNA clones were constructed and infectious SFTSV were recovered from co-transfected cells.Viral infectivity,growth kinetics,and viral protein expression profile of the rescued virus were compared with the laboratory-adapted virus.Focus formation assay showed that the size and morphology of the foci formed by the rescued SFTSV were indistinguishable with the laboratory-adapted virus.However,one-step growth curve and nucleoprotein expression analyses revealed the rescued virus replicated less efficiently than the laboratory-adapted virus.Sequence analysis indicated that the difference may be due to the mutations in the laboratory-adapted strain which are more prone to cell culture.The results help us to understand the molecular biology of SFTSV,and provide a useful tool for developing vaccines and antivirals against SFTS.

Optimization of Genetic Transformation System of Tobacco K326 Mediated by Agrobacterium

[Objective]The aim was to optimize genetic transformation system in tobacco K326 mediated by Agrobacterium.[Method]The leaf of tobacco aseptic seedling was taken as explants to study the optimization of Agrobacterium-mediated genetic transformation system.[Result] The highest transformation efficiency was obtained when the explants were pre-cultured in the medium of MS ＋ 2 mg/L 6-BA ＋ 0.2 mg/L IAA for 2 d,and then infected with Agrobacterium GV3101（OD600 =0.6） for 5 min.The PCR detection proved that npt II gene had been integrated into the regenerated tobacco plants.[Conclusion]A highly efficient genetic transformation system of tobacco leaf mediated by Agrobacterium was established.

GENETIC OPTIMIZATION OF HOT FILAMENT PARAMETERS IN HFCVD SYSTEM

In HFCVD system the substrate temperature is a key factor which deeply affects the quality of diamond films. Th e magnitude and the variation of the substrate temperature must be limited in a suitable range to deposit diamond films of uniform thickness over large areas. In this paper, the hot filament parameters are investigated on the basi s of GAs to realize a good substrate temperature profile. Computer simulations d emonstrate that on parameters optimized by GAs a uniform substrate temperatur e field can be formed over a relatively large circle area with R s=10 cm.

Establishment of the Agrobacterium-mediated Genetic Transformation System of Ginkgo biloba and the Construction of the Expression Vector of Gb-DXR

[Objective] The research aimed to provide reference for increasing the genetic transformation efficiency of Ginkgo biloba mediated by Agrobacterium.[Method] Taking the mature embryos of Ginkgo biloba seeds as explants,after 48 hours＇ pre-cultivation on MS medium in the absence of phytohormone,GUS gene was transmitted into embryos of Ginkgo biloba mediated by three kinds of Agrobacterium.Transient expression of GUS gene activity was observed through histochemical staining,and the influencing factors of the expression of GUS gene were analyzed.And the expression vector of 1-deoxy-D-xylulose-5-phosphate reductoisomerase in the biosynthesis approach of biobalide precursor of Ginkgo biloba was constructed.[Result] A more suitable genetic transformation scheme was obtained as follows：taking embryos of Ginkgo biloba as explants,using EHA105 Agrobacterium with pCAMBIA1304＋ for infection,co-culture for 3 days and GUS staining.The results showed that transient expression rate of GUS after transformation was higher.[Conclusion] The research provide a more effective method for further study on the transgene of Ginkgo biloba.

FUZZY GLOBAL SLIDING MODE CONTROL BASED ON GENETIC ALGORITHM AND ITS APPLICATION FOR FLIGHT SIMULATOR SERVO SYSTEM

To alleviate the chattering problem, a new type of fuzzy global sliding mode controller （FGSMC） is presented. In this controller, the switching gain is estimated by fuzzy logic system based on the reachable conditions of sliding mode controller（SMC）, and genetic algorithm （GA） is used to optimize scaling factor of the switching gain, thus the switch chattering of SMC can be alleviated. Moreover, global sliding mode is realized by designing an exponential dynamic sliding surface. Simulation and real-time application for flight simulator servo system with Lugre friction are given to indicate that the proposed controller can guarantee high robust performance all the time and can alleviate chattering phenomenon effectively.

Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literature evidences, with particular attention to sorafenib and regorafenib, which have been used longer than the others in HCC treatment.

Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review

AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.

A Linear Domain System Identification for Small Unmanned Aerial Rotorcraft Based on Adaptive Genetic Algorithm

This paper proposes a new adaptive linear domain system identification method for small unmanned aerial rotorcraft.Byusing the flash memory integrated into the micro guide navigation control module, system records the data sequences of flighttests as inputs (control signals for servos) and outputs (aircraft’s attitude and velocity information).After data preprocessing, thesystem constructs the horizontal and vertical dynamic model for the small unmanned aerial rotorcraft using adaptive geneticalgorithm.The identified model is verified by a series of simulations and tests.Comparison between flight data and the one-stepprediction data obtained from the identification model shows that the dynamic model has a good estimation for real unmannedaerial rotorcraft system.Based on the proposed dynamic model, the small unmanned aerial rotorcraft can perform hovering,turning, and straight flight tasks in real flight tests.

Improved Ant Colony-Genetic Algorithm for Information Transmission Path Optimization in Remanufacturing Service System

The information transmission path optimization(ITPO) can often a ect the e ciency and accuracy of remanufactur?ing service. However, there is a greater degree of uncertainty and complexity in information transmission of remanu?facturing service system, which leads to a critical need for designing planning models to deal with this added uncer?tainty and complexity. In this paper, a three?dimensional(3D) model of remanufacturing service information network for information transmission is developed, which combines the physic coordinate and the transmitted properties of all the devices in the remanufacturing service system. In order to solve the basic ITPO in the 3D model, an improved 3D ant colony algorithm(Improved AC) was put forward. Moreover, to further improve the operation e ciency of the algorithm, an improved ant colony?genetic algorithm(AC?GA) that combines the improved AC and genetic algorithm was developed. In addition, by taking the transmission of remanufacturing service demand information of certain roller as example, the e ectiveness of AC?GA algorithm was analyzed and compared with that of improved AC, and the results demonstrated that AC?GA algorithm was superior to AC algorithm in aspects of information transmission delay, information transmission cost, and rate of information loss.

Fractional order PID control for steer-by-wire system of emergency rescue vehicle based on genetic algorithm

Aiming at dealing with the difficulty for traditional emergency rescue vehicle(ECV)to enter into limited rescue scenes,the electro-hydraulic steer-by-wire(SBW)system is introduced to achieve the multi-mode steering of the ECV.The overall structure and mathematical model of the SBW system are described at length.The fractional order proportional-integral-derivative(FOPID)controller based on fractional calculus theory is designed to control the steering cylinder’s movement in SBW system.The anti-windup problem is considered in the FOPID controller design to reduce the bad influence of saturation.Five parameters of the FOPID controller are optimized using the genetic algorithm by maximizing the fitness function which involves integral of time by absolute value error(ITAE),peak overshoot,as well as settling time.The time-domain simulations are implemented to identify the performance of the raised FOPID controller.The simulation results indicate the presented FOPID controller possesses more effective control properties than classical proportional-integral-derivative(PID)controller on the part of transient response,tracking capability and robustness.

Optimal operation of water supply systems with tanks based on genetic algorithm

In view of the poor water supply system’s network properties, the system’s complicated network hydraulic equations were replaced by macroscopic nodal pressure model and the model of relationship between supply flow and water source head. By using pump-station pressure head and initial tank water levels as decision variables, the model of optimal allocation of water supply between pump-sources was developed. Genetic algorithm was introduced to deal with the model of optimal allocation of water supply. Methods for handling each constraint condition were put forward, and overcome the shortcoming such as premature convergence of genetic algorithm; a solving method was brought forward in which genetic algorithm was combined with simulated annealing technology and self-adaptive crossover and mutation probabilities were adopted. An application example showed the feasibility of this algorithm.

Sequencing Mixed-model Production Systems by Modified Multi-objective Genetic Algorithms

As two independent problems,scheduling for parts fabrication line and sequencing for mixed-model assembly line have been addressed respectively by many researchers.However,these two problems should be considered simultaneously to improve the efficiency of the whole fabrication/assembly systems.By far,little research effort is devoted to sequencing problems for mixed-model fabrication/assembly systems.This paper is concerned about the sequencing problems in pull production systems which are composed of one mixed-model assembly line with limited intermediate buffers and two flexible parts fabrication flow lines with identical parallel machines and limited intermediate buffers.Two objectives are considered simultaneously：minimizing the total variation in parts consumption in the assembly line and minimizing the total makespan cost in the fabrication/assembly system.The integrated optimization framework,mathematical models and the method to construct the complete schedules for the fabrication lines according to the production sequences for the first stage in fabrication lines are presented.Since the above problems are non-deterministic polynomial-hard（NP-hard）,a modified multi-objective genetic algorithm is proposed for solving the models,in which a method to generate the production sequences for the fabrication lines from the production sequences for the assembly line and a method to generate the initial population are put forward,new selection,crossover and mutation operators are designed,and Pareto ranking method and sharing function method are employed to evaluate the individuals＇ fitness.The feasibility and efficiency of the multi-objective genetic algorithm is shown by computational comparison with a multi-objective simulated annealing algorithm.The sequencing problems for mixed-model production systems can be solved effectively by the proposed modified multi-objective genetic algorithm.

Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Optimization and Sizing for Propulsion System of Liquid Rocket Using Genetic Algorithm

Flight vehicle conceptual design appears to be a promising area for application of the Genetic Algorithm （GA） as an approach to help to automate part of the design process. This computational research effort strives to develop a propulsion system design strategy for liquid rocket to optimize take-off mass, satisfying the mission range under the constraint of axial overload. The method by which this process is accomplished by using GA as optimizer is outlined in this paper. Convergence of GA is improved by introducing initial population based on Design of Experiments Technique.

A Hybrid Genetic Algorithm for Reduct of Attributes in Decision System Based on Rough Set Theory

Knowledge reduction is an important issue when dealing with huge amounts of data. And it has been proved that computing the minimal reduct of decision system is NP-complete. By introducing heuristic information into genetic algorithm, we proposed a heuristic genetic algorithm. In the genetic algorithm, we constructed a new operator to maintaining the classification ability. The experiment shows that our algorithm is efficient and effective for minimal reduct, even for the special example that the simple heuristic algorithm can’t get the right result.