DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital Heart Diseases

Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little attention.Monozygotic(MZ)twins with CHD provide a unique model for exploring this phenomenon.In order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated pathways.To further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were analyzed.We identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling pathways.The methylation changes of calcium signaling genes might be related to VSD pathogenesis.Conclusion:CHD is associated with differential DNA methylation in MZ twins.CHD may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.

Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants.CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.

Digital Twins for Wastewater Treatment:A Technical Review

The digital twins concept enhances modeling and simulation through the integration of real-time data and feedback.This review elucidates the foundational elements of digital twins,covering their concept,entities,domains,and key technologies.More specifically,we investigate the transformative potential of digital twins for the wastewater treatment engineering sector.Our discussion highlights the application of digital twins to wastewater treatment plants(WWTPs)and sewage networks,hardware(i.e.,facilities and pipes,sensors for water quality and activated sludge,hydrodynamics,and power consumption),and software(i.e.,knowledge-based and data-driven models,mechanistic models,hybrid twins,control methods,and the Internet of Things).Furthermore,two cases are provided,followed by an assessment of current challenges in and perspectives on the application of digital twins in WWTPs.This review serves as an essential primer for wastewater engineers navigating the digital paradigm shift.

A digital twins enabled underwater intelligent internet vehicle path planning system via reinforcement learning and edge computing

The Autonomous Underwater Glider(AUG)is a kind of prevailing underwater intelligent internet vehicle and occupies a dominant position in industrial applications,in which path planning is an essential problem.Due to the complexity and variability of the ocean,accurate environment modeling and flexible path planning algorithms are pivotal challenges.The traditional models mainly utilize mathematical functions,which are not complete and reliable.Most existing path planning algorithms depend on the environment and lack flexibility.To overcome these challenges,we propose a path planning system for underwater intelligent internet vehicles.It applies digital twins and sensor data to map the real ocean environment to a virtual digital space,which provides a comprehensive and reliable environment for path simulation.We design a value-based reinforcement learning path planning algorithm and explore the optimal network structure parameters.The path simulation is controlled by a closed-loop model integrated into the terminal vehicle through edge computing.The integration of state input enriches the learning of neural networks and helps to improve generalization and flexibility.The task-related reward function promotes the rapid convergence of the training.The experimental results prove that our reinforcement learning based path planning algorithm has great flexibility and can effectively adapt to a variety of different ocean conditions.

Game theory in network security for digital twins in industry

To ensure the safe operation of industrial digital twins network and avoid the harm to the system caused by hacker invasion,a series of discussions on network security issues are carried out based on game theory.From the perspective of the life cycle of network vulnerabilities,mining and repairing vulnerabilities are analyzed by applying evolutionary game theory.The evolution process of knowledge sharing among white hats under various conditions is simulated,and a game model of the vulnerability patch cooperative development strategy among manufacturers is constructed.On this basis,the differential evolution is introduced into the update mechanism of the Wolf Colony Algorithm(WCA)to produce better replacement individuals with greater probability from the perspective of both attack and defense.Through the simulation experiment,it is found that the convergence speed of the probability(X)of white Hat 1 choosing the knowledge sharing policy is related to the probability(x0)of white Hat 2 choosing the knowledge sharing policy initially,and the probability(y0)of white hat 2 choosing the knowledge sharing policy initially.When y0?0.9,X converges rapidly in a relatively short time.When y0 is constant and x0 is small,the probability curve of the“cooperative development”strategy converges to 0.It is concluded that the higher the trust among the white hat members in the temporary team,the stronger their willingness to share knowledge,which is conducive to the mining of loopholes in the system.The greater the probability of a hacker attacking the vulnerability before it is fully disclosed,the lower the willingness of manufacturers to choose the"cooperative development"of vulnerability patches.Applying the improved wolf colonyco-evolution algorithm can obtain the equilibrium solution of the"attack and defense game model",and allocate the security protection resources according to the importance of nodes.This study can provide an effective solution to protect the network security for digital twins in the industry.

Origin of nucleation and growth of extension twins in grains unsuitably oriented for twinning during deformation of Mg-1%Al

A large number of anomalous extension twins,with low or even negative twinning Schmid factors,were found to nucleate and grow in a strongly textured Mg-1Al alloy during tensile deformation along the extruded direction.The deformation mechanisms responsible for this behaviour were investigated through in-situ electron back-scattered diffraction,grain reference orientation deviation,and slip trace-modified lattice rotation.It was found that anomalous extension twins nucleated mainly at the onset of plastic deformation at or near grain boundary triple junctions.They were associated with the severe strain incompatibility between neighbour grains as a result from the differentbasal slip-induced lattice rotations.Moreover,the anomalous twins were able to grow with the applied strain due to the continuous activation ofbasal slip in different neighbour grains,which enhanced the strain incompatibility.These results reveal the complexity of the deformation mechanisms in Mg alloys at the local level when deformed along hard orientations.

Survey on digital twins for Internet of Vehicles:Fundamentals,challenges,and opportunities

As autonomous vehicles and the other supporting infrastructures(e.g.,smart cities and intelligent transportation systems)become more commonplace,the Internet of Vehicles(IoV)is getting increasingly prevalent.There have been attempts to utilize Digital Twins(DTs)to facilitate the design,evaluation,and deployment of IoV-based systems,for example by supporting high-fidelity modeling,real-time monitoring,and advanced predictive capabilities.However,the literature review undertaken in this paper suggests that integrating DTs into IoV-based system design and deployment remains an understudied topic.In addition,this paper explains how DTs can benefit IoV system designers and implementers,as well as describes several challenges and opportunities for future researchers.

Digital Twins for Engineering Asset Management:Synthesis,Analytical Framework,and Future Directions

Effective engineering asset management(EAM)is critical to economic development and improving livability in society,but its complexity often impedes optimal asset functionalities.Digital twins(DTs)could revolutionize the EAM paradigm by bidirectionally linking the physical and digital worlds in real time.There is great industrial and academic interest in DTs for EAM.However,previous review studies have predominately focused on technical aspects using limited life-cycle perspectives,failing to holistically synthesize DTs for EAM from the managerial point of view.Based on a systematic literature review,we introduce an analytical framework for describing DTs for EAM,which encompasses three levels:DT 1.0 for technical EAM,DT 2.0 for technical-human EAM,and DT 3.0 for technical-environmental EAM.Using this framework,we identify what is known,what is unknown,and future directions at each level.DT 1.0 addresses issues of asset quality,progress,and cost management,generating technical value.It lacks multi-objective self-adaptive EAM,however,and suffers from high application cost.It is imperative to enable closed-loop EAM in order to provide various functional services with affordable DT 1.0.DT 2.0 accommodates issues of human-machine symbiosis,safety,and flexibility management,generating managerial value beyond the technical performance improvement of engineering assets.However,DT 2.0 currently lacks the automation and security of human-machine interactions and the managerial value related to humans is not prominent enough.Future research needs to align technical and managerial value with highly automated and secure DT 2.0.DT 3.0 covers issues of participatory governance,organization management,sustainable development,and resilience enhancement,generating macro social value.Yet it suffers from organizational fragmentation and can only address limited social governance issues.Numerous research opportunities exist to coordinate different stakeholders.Similarly,future research opportunities exist to develop DT 3.0 in a more open and complex system.

Exploring Alternatives to Create Digital Twins from and for Process Simulation

In this work,Digital Twins based on Neural Networks for the steady state production of styrene were generated.Thus,both the Aspen Technology AI Model Builder(alternative 1)and a homemade MS Excel VBA code connected to Aspen HYSYS and Aspen Plus(alternative 2)were used with this same aim.The raw data used for generating the Digital Twins were obtained from process simulations using Aspen HYSYS and/or Aspen Plus,which were connected through a recycle-like stream via automation for solving the entire simulation flowsheet.Aspen HYSYS was used for solving the pre-heating,reaction,and stabilization sections of the process whereas Aspen Plus ensured the computing of the separation and purification columns.Both alternatives led to an excellent prediction showing the capability of creating Digital Twins from and for process simulation.

Numerical simulation on size effect of copper with nano-scale twins

To understand the tensile deformation of electro-deposited Cu with nano-scale twins, a numerical study was carried out based on a conventional theory of mechanism-based strain gradient plasticity （CMSG）. The concept of twin lamella strengthening zone was used in terms of the cohesive interface model to simulate grain-boundary sliding and separation. The model included a number of material parameters, such as grain size, elastic modulus, plastic strain hardening exponent, initial yield stress, as well as twin lamellar distribution, which may contribute to size effects of twin layers in Cu polycrystalline. The results provide information to understand the mechanical behaviors of Cu with nano-scale growth twins.

一次大磁暴主相期间ENA氧与氢的分离及分布特征——TWINS卫星观测

本文采用基于ENA(Energetic Neutral Atoms)次生电子起始脉冲高度分布,统计拟合分离中能段ENA两种主要成分氢和氧的方法,研发了实现ENA氢与氧分离的TWINS卫星原始数据处理软件;其中所需要的脉高分布模型,参照已有理论公式,利用TWINS(Two Wide-angle Imaging Neutral-atom Spectrometers)卫星标定数据进行拟合确定未知参数,再加以计算得到.将上述方法用于TWINS卫星实测数据,分离得到一次大磁暴主相期间ENA-H和ENA-O微分通量随观测视线的分布及其随主相增长的变化.分析发现:(1)ENA-H与ENA-O微分通量的强度和随观测视线的分布特征都有明显差别,从某种角度反映出ENA之源的O^+与H^+离子强度和分布之间的差异;(2)接近主相极大时,ENA-H有很强的低高度发射(LAE,Low Altitude Emission),出现在磁地方时午夜前极光和亚极光纬度区,意味着该区域较强的等离子片和环电流质子沉降,进入到外层基底以下较低高度大气层;而ENA-O则未有明显LAE产生;ENA-O强通量观测视线主要穿过广大环电流区,磁地方时主要在午夜之后以及黄昏前和黎明前后;(3)在磁暴主相快速增长期,ENA-O平均总通量持续增大,而ENA-H同步减小,ENA-O与ENA-H平均总通量的比率随环电流指数Dst绝对值的增大而大致成正比增长.

Evolution of twins and texture and its effects on mechanical properties of AZ31 magnesium alloy sheets under different rolling process parameters

In order to investigate the dependence of microstructure and mechanical properties on the rolling process parameters, AZ31 magnesium alloy sheets with different grain sizes, basal texture intensities and twinning types were obtained using hot rolling at various temperatures and reductions. The volume fractions of the extension, contraction and secondary twins in the as-rolled sheets depend on the grain size. The highest volume fractions of three types of twins are obtained at 523 K under the reduction of 10% when the average grain size value is the maximum. The critical reductions for complete dynamic recrystallization are 30% at 523 K and 40% at 473 K. The increase of yield strength is ascribed to both grain-refinement strengthening and basal texture strengthening at the first stage. When the grain size does not decrease with increasing the reduction, the yield strength is mainly influenced by the texture weakening.

Tensile Properties of Cu with Deformation Twins Induced by SMAT

High density nano-scale deformation twins were introduced in the surface layer of Cu sample by means of surface mechanical attrition treatment （SMAT） at room temperature. The Cu sample with deformation twins shows a yield strength of about 470 MPa in tension tests. The significant strengthening may be attributed to the effective inhibition of slip dislocations by abundant twin boundaries.

利用差分体像素CT由TWINS卫星ENA成像反演暴时环电流离子三维分布

本文将体像素CT方法应用于TWINS卫星高能中性原子立体成像数据,重建环电流离子通量强度三维分布.为了克服卫星ENA成像可能存在的仪器偏差造成反演误差增大甚至迭代发散无解的问题,发展了差分ENA体像素CT反演方法.采用环电流离子分布理论模型和实际卫星观测几何构形进行模拟检验,证明了该方法的可靠性和优越性.利用此方法分析2012年7月15日磁暴(min Dst=-133nT)主相期间TWINS两颗卫星的实测ENA数据(能量范围4keV^50keV),反演得到环电流离子微分通量随L值/纬度/地方时的三维分布与能谱.所得离子通量呈现显著不对称的部分环电流特征,主要分布在低纬-赤道区磁午夜前后至黎明前数小时,L值约为3.5~6.5的区域;将反演得到的磁午夜后赤道区环电流离子通量能谱,与THEMIS卫星当地测量得到的此区域同时的能谱作比较,两者符合得很好;证明本文发展的差分体像素CT是由多卫星ENA二维图像重建暴时环电流离子分布的有效方法.

Effects of deformation twins on microstructure evolution,mechanical properties and corrosion behaviors in magnesium alloys-A review

Due to lattice reorientation,grain segmentation,induced recrystallization,twins play a very important role in regulating texture,refining grains,improving mechanical properties and corrosion resistance,and has received more extensive attention.Numerous studies have shown that{10-12}<10-11>tensile twins(TTWs)are easily activated in large quantities due to the lower critical resolve shear stresses(CRSS).Introduction of TTWs under uniaxial compression improved the strength,ductility,and formability of magnesium(Mg)alloys.Moreover,TTWs produced by multi-directional impact forging(MDIF)can optimize the microstructure by dividing grains and promoting recrystallization,resulting in significant improvement of mechanical properties.Although{10-11}<10-12>compressive twins(CTWs)and{10-11}-{10-12}double twins(DTWs)can promote dynamic recrystallization(DRX),they are also favorable nucleation sites for cracks.In addition,the type and volume fraction of twins can affect the corrosion resistance,and they also play different roles in the corrosion process of different Mg alloys.Twins have shown great potential for improving structure and properties,but a comprehensive and critical discussion of twins in Mg alloys is still lacking.Therefore,based on previous studies,this article reviews the common types and variants of twins in Mg alloys,influencing factors,and their effects on the microstructure,mechanical properties and corrosion resistance.In addition,some interesting ideas are being proposed for further research.

STRAIN INDUCED STRUCTURAL TRANSITION OF INTERFACES AND TWINS IN A HOT－DEFORMED DUAL－PHASE TIAL ALLOY

The structure characteristics of a2/γinterfaces and the features of deformation twins in a quasi-isothermal forged Ti-45Al-10Nb alloy were studied by highresolution transmission electron microscopy. Three types of strain induced a2/γinterfaces and two types of strain induced twin boundaries were identified The most,important features are high density of ledges and the existence of I/3[111] Frank partial dislocation. Mechanisms for the formation these interfaces were proposed Two types of deformation twins were observed These deformation twins always start from the ledges it seems that ledges at interfaces are important features of interfacial structure for the mechanical behavior of alloys.

Building the metaverse using digital twins at all scales,states,and relations

Developments in new-generation information technology have enabled Digital Twins to reshape the physical world into a virtual digital space and provide technical support for constructing the Metaverse.Metaverse objects can be at the micro-,meso-,or macroscale.The Metaverse is a complex collection of solid,liquid,gaseous,plasma,and other uncertain states.Additionally,the Metaverse integrates tangibles with social relations,such as interpersonal(friends,partners,and family)and social relations(ethics,morality,and law).This review introduces some principles and laws,such as broken windows theory,small-world phenomenon,survivor bias,and herd behavior,for constructing a Digital Twins model for social relations.Therefore,from multiple perspectives,this article reviews mappings of tangible and intangible real-world objects to the Metaverse using the Digital Twins model.

Promoting hybrid twins structure to reduce yield asymmetry of rolled AZ31 plates by combining side-rolling and torsion

In this work,an as-rolled AZ31 square bar with c-axis//ND(normal direction)texture was used.Side-rolling and reciprocating torsion were performed to treat the bar.Microstructure evolution and tensile-compressive properties were investigated in detail.Initial rolled AZ31 bar exhibits a large yield asymmetry along the rolling direction(RD).Reciprocating torsion can generate extension twins to introduce twin boundaries and twin-texture.The twin structure can reduce yield asymmetry.However,only limited regions in the rolled AZ31 bar can be twinned during torsion.Pre-side-rolling along the transverse direction(TD)can generate two texture components(c-axis//TD texture and c-axis//ND texture)by introducing profuse{10–12}twins.Such dual texture components help increase the regions which are favorable for twinning during torsion.Finally,combining side-rolling and reciprocating torsion generates hybrid{10–12}twins structure on the entire cross-section,resulting in a remarkably low yield asymmetry.The relevant mechanisms were discussed in detail.

Collaborative Clustering Parallel Reinforcement Learning for Edge-Cloud Digital Twins Manufacturing System

To realize high-accuracy physical-cyber digital twin(DT)mapping in a manufacturing system,a huge amount of data need to be collected and analyzed in real-time.Traditional DTs systems are deployed in cloud or edge servers independently,whilst it is hard to apply in real production systems due to the high interaction or execution delay.This results in a low consistency in the temporal dimension of the physical-cyber model.In this work,we propose a novel efficient edge-cloud DT manufacturing system,which is inspired by resource scheduling technology.Specifically,an edge-cloud collaborative DTs system deployment architecture is first constructed.Then,deterministic and uncertainty optimization adaptive strategies are presented to choose a more powerful server for running DT-based applications.We model the adaptive optimization problems as dynamic programming problems and propose a novel collaborative clustering parallel Q-learning(CCPQL)algorithm and prediction-based CCPQL to solve the problems.The proposed approach reduces the total delay with a higher convergence rate.Numerical simulation results are provided to validate the approach,which would have great potential in dynamic and complex industrial internet environments.

Early ultrasound diagnosis of conjoined twins at eight weeks of pregnancy: A case report

BACKGROUND Conjoined twins are a rare occurrence,and the majority of these malformations are detected during second trimester screening.CASE SUMMARY Herein we report a case of conjoined twins,which was diagnosed by ultrasound at 8 wk gestation and was normal at 7 wk gestation.The two fetuses shared one heart and were diagnosed as thoracopagus twins.This is the first report of conjoined twins diagnosed at 8 wk gestation.The pregnancy was terminated electively at 9 wk gestation.Because some congenital malformations can be diagnosed earlier,a prenatal ultrasound examination at an early gestational stage cannot be dismissed.CONCLUSION This case demonstrates that a 7-8 wk gestation might be the earliest period when conjoined twins can be diagnosed by ultrasound.