Development and Therapeutic Applications of Precise Gene Editing Technology

The advent of gene editing represents one of the most transformative breakthroughs in life science,making genome manipulation more accessible than ever before.While traditional CRISPR/Cas-based gene editing,which involves double-strand DNA breaks(DSBs),excels at gene disruption,it is less effective for accurate gene modification.The limitation arises because DSBs are primarily repaired via non-homologous end joining(NHEJ),which tends to introduce indels at the break site.While homology directed repair(HDR)can achieve precise editing when a donor DNA template is provided,the reliance on DSBs often results in unintended genome damage.HDR is restricted to specific cell cycle phases,limiting its application.Currently,gene editing has evolved to unprecedented levels of precision without relying on DSB and HDR.The development of innovative systems,such as base editing,prime editing,and CRISPR-associated transposases(CASTs),now allow for precise editing ranging from single nucleotides to large DNA fragments.Base editors(BEs)enable the direct conversion of one nucleotide to another,and prime editors(PEs)further expand gene editing capabilities by allowing for the insertion,deletion,or alteration of small DNA fragments.The CAST system,a recent innovation,allows for the precise insertion of large DNA fragments at specific genomic locations.In recent years,the optimization of these precise gene editing tools has led to significant improvements in editing efficiency,specificity,and versatility,with advancements such as the creation of base editors for nucleotide transversions,enhanced prime editing systems for more efficient and precise modifications,and refined CAST systems for targeted large DNA insertions,expanding the range of applications for these tools.Concurrently,these advances are complemented by significant improvements in in vivo delivery methods,which have paved the way for therapeutic application of precise gene editing tools.Effective delivery systems are critical for the success of gene therapies,and recent developments in both viral and non-viral vectors have improved the efficiency and safety of gene editing.For instance,adeno-associated viruses(AAVs)are widely used due to their high transfection efficiency and low immunogenicity,though challenges such as limited cargo capacity and potential for immune responses remain.Non-viral delivery systems,including lipid nanoparticles(LNPs),offer an alternative with lower immunogenicity and higher payload capacity,although their transfection efficiency can be lower.The therapeutic potential of these precise gene editing technologies is vast,particularly in treating genetic disorders.Preclinical studies have demonstrated the effectiveness of base editing in correcting genetic mutations responsible for diseases such as cardiomyopathy,liver disease,and hereditary hearing loss.These technologies promise to treat symptoms and potentially cure the underlying genetic causes of these conditions.Meanwhile,challenges remain,such as optimizing the safety and specificity of gene editing tools,improving delivery systems,and overcoming off-target effects,all of which are critical for their successful application in clinical settings.In summary,the continuous evolution of precise gene editing technologies,combined with advancements in delivery systems,is driving the field toward new therapeutic applications that can potentially transform the treatment of genetic disorders by targeting their root causes.

Tactical planning and optimization of a milk run system of parts pickup for an engine manufacturer

A real-life milk run system designing problem of an engine manufacturer adopted JIT(just-in-time)production is studied.In the process of milk run system planning and design,the supply base is identified and a supplier site map is plotted for an arrangement of routes on which parts are periodically collected in a JIT manner from many scattered suppliers.With unit load designing,vehicle choosing and fleet sizing,pickup routing,vehicle assigning and scheduling problems are studied.Among these problems,a CVRP problem is identified and formulated as the key optimization in designing this milk run system,and it is solved through an optimization process.This tactical planning and optimization process gives a good solution to the real problem,and may shed light on the planning of similar systems.

Sensor Registration in Asynchronous Data Fusion

To find an effective method to estimate and remove the registration error in asynchronous multisensor system, Kalman filtering technique and least squares approach have been proposed to estimate and remove sensor bias and sensor frame tilt errors in multisensor systems with asynchronous data. Simulation results is presented to demonstrate the performance of these approaches. The least squares approach can compress measurements to any time. The Kalman filter algorithm can detect registration errors and use the information to converge tracks from independent sensors. This is particularly important if the data from the sensors are to be fused.

Kalman Fliter Approach to Multisensor Registration of Moving Platform

Aim To find an effective method to remove the registration error in multi-sensor systems. Methods A Kalman filtering technique was proposed to estimate and remove sensor bias and sensor fare tilt errors in multisensor systems with a moving platform. Results Simulation results are presented to demonstrate the performance of the approach. Conclusion The Kalman filter algorithm am detect registration errors and use this information to converge tracks from independent sensors. This is particularly important if the data from the sensors are to fused.

Ground Alignment of Inertial Navigation System with the Aid of GPS Signals

Due to the poor observability of INS ground self alignment, only horizontal alignment is satisfied. This paper proposes using GPS double difference carrier phase as external reference to improve the observability of INS self alignment. Through observability analysis and computer simulation, it is demonstrated that the azimuth alignment is as quick as horizontal alignment, the accuracy of horizontal alignment is improved, and the gyros errors can be estimated quickly and precisely.

Initial Alignment Technique for SINS of Vehicles in the Moving State

An initial alignment technique for the strapdown inertial navigation system (SINS) of vehicles in the moving state is researched. By selecting an odometer as the system’s external sensor, the mathematical model for the alignment in the moving state is established and the observability of the system is analyzed. The results show that the SINS can successfully achieve the precision alignment in 10 min when the vehicle is moving toward the prearranged place after its staying for several seconds to perform the coarse alignment. The precision of alignment can also be improved in the moving state compared with that in the static state.

Finite element model updating and validating of Runyang Suspension Bridge based on SHMS

Based on the finite element （FE） program ANSYS, a three-dimensional model for the Runyang Suspension Bridge （RSB） is established. The structural natural frequency, vibration mode, stress and displacement response under various load cases are given. A new method of FE model updating is presented based on the physical meaning of sensitivity and the penalty function concept. In this method, the structural model is updated by modifying the parameters of design, and validated by structural natural vibration characteristics, stress response as well as displacement response. The design parameters used for updating are bounded according to measured static response and engineering judgment. The FE model of RSB is updated and validated by the measurements coming from the structural health monitoring system （SHMS）, and the FE baseline model reflecting the current state of RSB is achieved. Both the dynamic and static results show that the method is effective in updating the FE model of long span suspension bridges. The results obtained provide an important research basis for damage alarming and health monitoring of the RSB.

Design of super-orthogonal space-time trellis codes based on trace criterion

A design of super-orthogonal space-time trellis codes （SOSTTCs） based on the trace criterion （TC） is proposed for improving the design of SOSTTCs. The shortcomings of the rank and determinant criteria based design and the advantages of the TC-based design are analyzed. The optimization principle of four factors is presented, which includes the space-time block coding （STBC） scheme, set partitioning, trellis structure, and the assignment of signal subsets and STBC schemes in the trellis. According to this principle, systematical and handcrafted design steps are given in detail. By constellation expansion, the code performance can be further improved. The code design results are given, and the new codes outperform others in the simulation.

NOVEL GENERALIZED GREY INCIDENCE MODEL BASED ON INTERVAL GREY NUMBERS

To extend the traditional generalized grey incidence model, a novel grey incidence model based on inter- val grey numbers is constructed. Considering the numerical information of indexes cannot be accurately obtained and can be defined as interval grey numbers, the interval grey numbers are defined as standard interval grey num- bers which are split in white part and grey part. The absolute degree of incidence and relative degree of incidence based on the interval grey numbers are constructed and their arithmetic are given. Finally, an example about commercial aircraft index selection illuminates the effectiveness of the model. The results show that the model can sort indexes better and can extend the grey incidence models significantly.

Importance and Design Requirements of Equipotential Connection in Lightning Protection Engineering

The role played by equipotential connection in lightning protection was summarized in terms of lightning protection,static electricity,electromagnetic shielding,protection from electric shocks,and earth fault protection.In addition,drawbacks of independent grounding and common grounding were concluded.According to standards and researches,such as Building Lightning Protection Design Standard （GB50057-2010）,further demands and rules of equipotential connection in lightning protection engineering were proposed,providing references for lightning prevention design,construction and examination by related scientific workers and staffs.

Research Progress of the Planning Methods of Prior Conservation Areas

The planning of prior conservation areas is an important part of nature re- serve system, ：it is of great significance for biodiversity conservation. The methods of priority planning include hot-spots analysis, gap analysis, systematic conservation planning analysis and multi-criteria decision analysis. The key issues of priority area planning include the determination of the protect objects, the analyses of the protec- tion value and protection cost, the win-win development of protection and economy, and the changes of the management strategies of the protected areas. In this study, the features and research progress of different conservation methods were analyzed, and based on the discussion on the key issues of the planning of the protected areas, the application prospect of different methods was analyzed.

Research on basic characteristics of complex system brittleness

The goal of this paper is to research one new characteristic of complex system. Brittleness, which is one new characteritic of complex system, is presented in this paper. The linguistic and qualitative descriptions of complex system are also given in this paper. Otherwise, the qualitative description of complex system is presented at first. On the basis of analyzing the existing brittleness problems, linguistic description and mathematic description of brittleness are given as well. Three kinds of phenomena to judge brittleness of complex system are also given, based on catastrophe theory. Basic characteristics of brittleness are given on the basis of its mathematic description. Two critical point sets are defined by using catastrophe theory. The definition of brittleness and its related theory can serve the control of complex system, and provide theoretical basis for the design and control of complex system.

Weak-Coupling Theory for Semiclassical Periodically Driven Two-Level Systems： Beyond Rotating-Wave Approximation

We present a weak-coupling theory of semiclassical periodically driven two-level systems. The explicit analytical approximating solution is shown to reproduce highly accurately the exact results well beyond the regime of the rotating-wave approximation.

Standards of Ecological Compensation for Traditional Ecoagriculture:Taking Rice-Fish System in Hani Terrace as an Example

Traditional eco-agriculture provides many ecosystem services which are important for the local environment, especially in mountain areas. In order to encourage the farmers to engage in coo-agriculture, it is necessary to establish an eco-compensation mechanism for them. As the compensation standard is one of key issues in establishing eeo-compensation mechanism, this paper calculated the standard based on the farmers＇ willingness to accept （WTA） and the input-output analysis of eco-compensation. We took the traditional rice-fish eco-agriculture as the research object, conducting field surveys in Hani Terrace of Honghe County. Through the questionnaires in 2o11, we obtained the farmers＇ willingness to accept government compensation and market compensation. Then, the research evaluated the output of eco-compensation, the economic value of rice-fish paddy ecosystem services. Finally, under different market compensation standards, we compared the input and output of government compensation. The results show that, in 2011 the government should to pay farmers 7462 yuan.ha^-1·a^-1 to meet their willingness, but the output （ecological benefit） was only 7393 yuan.ha^-1·a^-1. However, whenthe rice price increases 1 yuan·kg-1 because of the limited use of chemicals in the next year, the government just has to pay farmers 4062 yuan.ha^-1·a^-1 and the surplus will be 3331 yuan.ha^-1·a^-1.

Roll-to-roll imprint for high precision grating manufacturing

In this paper,a novel roll-to-roll imprint process is proposed to fabricate gratings in large area. The key challenges in roll-to-roll imprint process,such as the roller mold preparation,imprint system,misalignment of imprint roller and backup roller,and also the imprint pressure,are investigated. Various gratings with different periods and profiles are obtained by the roll-to-roll process. To calibrate the measuring ability of the self-made grating by imprint,a calibration system is built with a dual-frequency laser interferometer. By the calibration,the self-made gratings can achieve ±4μm accuracy in 45mm measuring distance.

Calibration of split Hopkinson pressure bar system with special shape striker

In order to present basic guidance for system calibration of split Hopkinson pressure bar(SHPB) with the special shape striker,wave characteristics and dynamic responses of SHPB under striker impact were analyzed.Stress generated by the special shape striker tends to have a half-sine waveform and has little wave dispersion during its propagation.Impact velocities of the special shape striker and peak values of generated stress still have linear relation but with a different coefficient from that of cylindrical strikers.From stress histories on the surfaces of the input bar impacted by the special shape striker off-axially and obliquely,it is found that the misalignment impacts usually trigger wave distortion and amplitude decrease,which can be used to identify the poor system adjustment.Finally,the system calibration of SHPB with the special shape striker can be classified into four steps:system adjustment,wave distortion identification,measurement calibration and transmission calibration,where the measurement calibration factor and transmission calibration factor are elaborated and redefined.

Unified Symmetry of Hamilton Systems

The definition and the criterion of a unified symmetry for a Hamilton system are presented. The sufficient condition under which the Noether symmetry is a unified symmetry for the system is given. A new conserved quantity,as well as the Noether conserved quantity and the Hojman conserved quantity, deduced from the unified symmetry, is obtained. An example is finally given to illustrate the application of the results.

System reliability analysis of seismic pseudo-static stability of rock wedge based on nonlinear Barton–Bandis criterion

Based on the nonlinear Barton–Bandis(B–B)failure criterion,this study considers the system reliability of rock wedge stability under the pseudo-static seismic load.The failure probability(Pf)of the system is calculated based on the Monte−Carlo method when considering parameter correlation and variability.Parameter analysis and sensitivity analysis are carried out to explore the influence of parameters on reliability.The relationships among the failure probability,safety factor(Fs),and variation coefficient are explored,and then stability probability curves of the rock wedge under the pseudo-static seismic load are drawn.The results show that the parameter correlation of the B–B failure criterion has a significant influence on the failure probability,but correlation increases system reliability or decreases system reliability affected by other parameters.Under the pseudo-static seismic action,sliding on both planes is the main failure mode of wedge system.In addition,the parameters with relatively high sensitivity are two angles related to the joint dip.When the coefficient of variation is consistent,the probability of system failure is a function of the safety factor.

Characteristics of Period—Doubling Bifurcation Cascades in Quasi—discontinuous Systems

Many systems can display a very short, rapid change stage (quasi-discontinuous region) inside a relatively very long and slow change process. A quantitative definition for the 'quasi-discontinuity' in these systems has been introduced. With the aid of a simplified model, some extraordinary Feigenbaum constants have been found inside the period-doubling cascades, the relationship between the values of the extraordinary Feigenbaum constants and the quasi-discontinuity of the system has also been reported. The phenomenon has been observed in Pikovsky circuit and Rose-Hindmash model.

Perturbation to Symmetries and Adiabatic Invariants of Nonholonomic System in Terms of Quasi-coordinates

Based on the theory of Lie symmetries and conserved quantities, the exact invariants and adiabatic invariants of nonholonomic system in terms of quasi-coordinates are studied. The perturbation to symmetries for the nonholonomic system in terms of quasi-coordinates under small excitation is discussed. The concept of high-order adiabatic invariant is presented, and the forms of exact invariants and adiabatic invariants as well as the conditions for their existence are given. Then the corresponding inverse problem is studied.