Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

Research status and application of artificial intelligence large models in the oil and gas industry

This article elucidates the concept of large model technology,summarizes the research status of large model technology both domestically and internationally,provides an overview of the application status of large models in vertical industries,outlines the challenges and issues confronted in applying large models in the oil and gas sector,and offers prospects for the application of large models in the oil and gas industry.The existing large models can be briefly divided into three categories:large language models,visual large models,and multimodal large models.The application of large models in the oil and gas industry is still in its infancy.Based on open-source large language models,some oil and gas enterprises have released large language model products using methods like fine-tuning and retrieval augmented generation.Scholars have attempted to develop scenario-specific models for oil and gas operations by using visual/multimodal foundation models.A few researchers have constructed pre-trained foundation models for seismic data processing and interpretation,as well as core analysis.The application of large models in the oil and gas industry faces challenges such as current data quantity and quality being difficult to support the training of large models,high research and development costs,and poor algorithm autonomy and control.The application of large models should be guided by the needs of oil and gas business,taking the application of large models as an opportunity to improve data lifecycle management,enhance data governance capabilities,promote the construction of computing power,strengthen the construction of“artificial intelligence+energy”composite teams,and boost the autonomy and control of large model technology.

Evolution and Prospects of Foundation Models: From Large Language Models to Large Multimodal Models

Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.

Frontogenesis and Frontolysis of a Cold Filament Driven by the Cross-Filament Wind and Wave Fields Simulated by a Large Eddy Simulation

The variations of the frontogenetic trend of a cold filament induced by the cross-filament wind and wave fields are studied by a non-hydrostatic large eddy simulation. Five cases with different strengths of wind and wave fields are studied.The results show that the intense wind and wave fields further break the symmetries of submesoscale flow fields and suppress the levels of filament frontogenesis. The changes of secondary circulation directions—that is, the conversion between the convergence and divergence of the surface cross-filament currents with the downwelling and upwelling jets in the filament center—are associated with the inertial oscillation. The filament frontogenesis and frontolysis caused by the changes of secondary circulation directions may periodically sharpen and smooth the gradient of submesoscale flow fields.The lifecycle of the cold filament may include multiple stages of filament frontogenesis and frontolysis.

Optimization of Fixture Number in Large Thin-Walled Parts Assembly Based on IPSO

There are lots of researches on fixture layout optimization for large thin-walled parts.Current researches focus on the positioning problem,i.e.,optimizing the positions of a constant number of fixtures.However,how to determine the number of fixtures is ignored.In most cases,the number of fixtures located on large thin-walled parts is determined based on engineering experience,which leads to huge fixture number and extra waste.Therefore,this paper constructs an optimization model to minimize the number of fixtures.The constraints are set in the optimization model to ensure that the part deformation is within the surface profile tolerance.In addition,the assembly gap between two parts is also controlled.To conduct the optimization,this paper develops an improved particle swarm optimization(IPSO)algorithm by integrating the shrinkage factor and adaptive inertia weight.In the algorithm,particles are encoded according to the fixture position.Each dimension of the particle is assigned to a sub-region by constraining the optional position range of each fixture to improve the optimization efficiency.Finally,a case study on ship curved panel assembly is provided to prove that our method can optimize the number of fixtures while meeting the assembly quality requirements.This research proposes a method to optimize the number of fixtures,which can reduce the number of fixtures and achieve deformation control at the same time.

Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish(Danio rerio)

Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes.However,their activity markedly diminishes with payloads exceeding 11 kb.Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs,improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics,metabolic engineering,and transgenic animal production.In this study,we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer(QBI SP163,ST)and enhanced the nuclear targeting ability using the nuclear localization protein H2B(SHT).The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures(H1299),comparable to the well-established super PiggyBac system.Furthermore,mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads(8 kb,14 kb,and 24 kb)into zebrafish(Danio rerio).This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.

Shallow Convection Dataset Simulated by Three Different Large Eddy Models

Shallow convection plays an important role in transporting heat and moisture from the near-surface to higher altitudes,yet its parameterization in numerical models remains a great challenge,partly due to the lack of high-resolution observations.This study describes a large eddy simulation(LES)dataset for four shallow convection cases that differ primarily in inversion strength,which can be used as a surrogate for real data.To reduce the uncertainty in LES modeling,three different large eddy models were used,including SAM(System for Atmospheric Modeling),WRF(Weather Research and Forecasting model),and UCLA-LES.Results show that the different models generally exhibit similar behavior for each shallow convection case,despite some differences in the details of the convective structure.In addition to grid-averaged fields,conditionally sampled variables,such as in-cloud moisture and vertical velocity,are also provided,which are indispensable for calculation of the entrainment/detrainment rate.Considering the essentiality of the entraining/detraining process in the parameterization of cumulus convection,the dataset presented in this study is potentially useful for validation and improvement of the parameterization of shallow convection.

The Immense Impact of Reverse Edges on Large Hierarchical Networks

Hierarchical networks are frequently encountered in animal groups,gene networks,and artificial engineering systems such as multiple robots,unmanned vehicle systems,smart grids,wind farm networks,and so forth.The structure of a large directed hierarchical network is often strongly influenced by reverse edges from lower-to higher-level nodes,such as lagging birds’howl in a flock or the opinions of lowerlevel individuals feeding back to higher-level ones in a social group.This study reveals that,for most large-scale real hierarchical networks,the majority of the reverse edges do not affect the synchronization process of the entire network;the synchronization process is influenced only by a small part of these reverse edges along specific paths.More surprisingly,a single effective reverse edge can slow down the synchronization of a huge hierarchical network by over 60%.The effect of such edges depends not on the network size but only on the average in-degree of the involved subnetwork.The overwhelming majority of active reverse edges turn out to have some kind of“bunching”effect on the information flows of hierarchical networks,which slows down synchronization processes.This finding refines the current understanding of the role of reverse edges in many natural,social,and engineering hierarchical networks,which might be beneficial for precisely tuning the synchronization rhythms of these networks.Our study also proposes an effective way to attack a hierarchical network by adding a malicious reverse edge to it and provides some guidance for protecting a network by screening out the specific small proportion of vulnerable nodes.

Acetylacetone-TiO_(2) Promoted Large Area Compatible Cascade Electron Transport Bilayer for Efficient Perovskite Solar Cells

In designing efficient perovskite solar cells(PSCs),the selection of suitable electron transport layers(ETLs)is critical to the final device performance as they determine the driving force for selective charge extraction.SnO_(2)nanoparticles(NPs)based ETLs have been a popular choice for PSCs due to superior electron mobility,but their relatively deep-lying conduction band energy levels(ECB)result in substantial potential loss.Meanwhile,TiO_(2)NPs establish favorable band alignment owing to shallower ECB,but their low intrinsic mobility and abundant surface trap sites impede the final performance.For this reason,constructing a cascaded bilayer ETL is highly desirable for efficient PSCs,as it can rearrange energy levels and exploit on advantages of an individual ETL.In this study,we prepare SnO_(2)NPs and acetylacetone-modified TiO_(2)(Acac-TiO_(2))NPs and implement them as bilayer SnO_(2)/Acac-TiO_(2)(BST)ETL,to assemble cascaded energy band structure.SnO_(2)contributes to rapid charge carrier transport from high electron mobility while Acac-TiO_(2)minimizes band-offset and effectively suppresses interfacial recombination.Accordingly,the optimized BST ETL generates synergistic influence and delivers power conversion efficiency(PCE)as high as 23.14%with open-circuit voltage(V_(oc))reaching 1.14 V.Furthermore,the BST ETL is transferred to a large scale and the corresponding mini module demonstrates peak performance of 18.39%PCE from 25 cm^(2)aperture area.Finally,the BST-based mini module exhibit excellent stability,maintaining 83.1%of its initial efficiency after 1000 h under simultaneous 1 Sun light-soaking and damp heat(85℃/RH 85%)environment.

Computing large deviation prefactors of stochastic dynamical systems based on machine learning

We present a large deviation theory that characterizes the exponential estimate for rare events in stochastic dynamical systems in the limit of weak noise.We aim to consider a next-to-leading-order approximation for more accurate calculation of the mean exit time by computing large deviation prefactors with the aid of machine learning.More specifically,we design a neural network framework to compute quasipotential,most probable paths and prefactors based on the orthogonal decomposition of a vector field.We corroborate the higher effectiveness and accuracy of our algorithm with two toy models.Numerical experiments demonstrate its powerful functionality in exploring the internal mechanism of rare events triggered by weak random fluctuations.

THE OPTIMAL LARGE TIME BEHAVIOR OF3D QUASILINEAR HYPERBOLIC EQUATIONS WITH NONLINEAR DAMPING

We are concerned with the large-time behavior of 3D quasilinear hyperbolic equations with nonlinear damping.The main novelty of this paper is two-fold.First,we prove the optimal decay rates of the second and third order spatial derivatives of the solution,which are the same as those of the heat equation,and in particular,are faster than ones of previous related works.Second,for well-chosen initial data,we also show that the lower optimal L^(2) convergence rate of the k(∈[0,3])-order spatial derivatives of the solution is(1+t)^(-(2+2k)/4).Therefore,our decay rates are optimal in this sense.The proofs are based on the Fourier splitting method,low-frequency and high-frequency decomposition,and delicate energy estimates.

Multi-environment BSA-seq using large F3 populations is able to achieve reliable QTL mapping with high power and resolution: An experimental demonstration in rice

Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq to detect QTL is often limited by inappropriate experimental designs, as evidenced by numerous practical studies. Most BSA-seq studies have utilized small to medium-sized populations, with F2populations being the most common choice. Nevertheless, theoretical studies have shown that using a large population with an appropriate pool size can significantly enhance the power and resolution of QTL detection in BSA-seq, with F_(3)populations offering notable advantages over F2populations. To provide an experimental demonstration, we tested the power of BSA-seq to identify QTL controlling days from sowing to heading(DTH) in a 7200-plant rice F_(3)population in two environments, with a pool size of approximately 500. Each experiment identified 34 QTL, an order of magnitude greater than reported in most BSA-seq experiments, of which 23 were detected in both experiments, with 17 of these located near41 previously reported QTL and eight cloned genes known to control DTH in rice. These results indicate that QTL mapping by BSA-seq in large F_(3)populations and multi-environment experiments can achieve high power, resolution, and reliability.

Tree mycorrhizal associations determine how biodiversity,large trees,and environmental factors drive aboveground carbon stock in temperate forests

Biodiversity,large trees,and environmental conditions such as climate and soil have important effects on forest carbon stocks.However,recent studies in temperate forests suggest that the relative importance of these factors depends on tree mycorrhizal associations,whereby large-tree effects may be driven by ectomycorrhizal(EM)trees,diversity effects may be driven by arbuscular mycorrhizal(AM)trees,and environment effects may depend on differential climate and soil preferences of AM and EM trees.To test this hypothesis,we used forest-inventory data consisting of over 80,000 trees from 631 temperate-forest plots(30 m×30 m)across Northeast China to examine how biodiversity(species diversity and ecological uniqueness),large trees(top 1%of tree diameters),and environmental factors(climate and soil nutrients)differently regulate aboveground carbon stocks of AM trees,EM trees,and AM and EM trees combined(i.e.total aboveground carbon stock).We found that large trees had a positive effect on both AM and EM tree carbon stocks.However,biodiversity and environmental factors had opposite effects on AM vs.EM tree carbon stocks.Specifically,the two components of biodiversity had positive effects on AM tree carbon stocks,but negative effects on EM tree carbon stocks.Environmental heterogeneity(mean annual temperature and soil nutrients)also exhibited contrasting effects on AM and EM tree carbon stocks.Consequently,for the total carbon stock,the positive large-tree effect far surpasses the diversity and environment effect.This is mainly because when integrating AM and EM tree carbon stock into total carbon stock,the opposite diversity-effect(also environment-effect)on AM vs.EM tree carbon stock counteracts each other while the consistent positive large-tree effect on AM and EM tree carbon stock is amplified.In summary,this study emphasized a mycorrhizal viewpoint to better understand the determinants of overarching aboveground carbon profile across regional forests.

DeBERTa-GRU: Sentiment Analysis for Large Language Model

Modern technological advancements have made social media an essential component of daily life.Social media allow individuals to share thoughts,emotions,and ideas.Sentiment analysis plays the function of evaluating whether the sentiment of the text is positive,negative,neutral,or any other personal emotion to understand the sentiment context of the text.Sentiment analysis is essential in business and society because it impacts strategic decision-making.Sentiment analysis involves challenges due to lexical variation,an unlabeled dataset,and text distance correlations.The execution time increases due to the sequential processing of the sequence models.However,the calculation times for the Transformer models are reduced because of the parallel processing.This study uses a hybrid deep learning strategy to combine the strengths of the Transformer and Sequence models while ignoring their limitations.In particular,the proposed model integrates the Decoding-enhanced with Bidirectional Encoder Representations from Transformers(BERT)attention(DeBERTa)and the Gated Recurrent Unit(GRU)for sentiment analysis.Using the Decoding-enhanced BERT technique,the words are mapped into a compact,semantic word embedding space,and the Gated Recurrent Unit model can capture the distance contextual semantics correctly.The proposed hybrid model achieves F1-scores of 97%on the Twitter Large Language Model(LLM)dataset,which is much higher than the performance of new techniques.

Effect of annealing temperature on microstructure and mechanical properties of Mg-Zn-Zr-Nd alloy with large final rolling deformation

In this study,the Mg-3Zn-0.5Zr-χNd(χ=0,0.6)alloys were subjected to final rolling treatment with large deformation of 50%.The impact of annealing temperatures on the microstructure and mechanical properties was investigated.The rolled Mg-3Zn-0.5Zr-0.6Nd alloy exhibited an ultimate tensile strength of 386 MPa,a yield strength of 361 MPa,and an elongation of 7.1%.Annealing at different temperatures resulted in reduced strength and obviously increased elongation for both alloys.Optimal mechanical properties for the Mg-3Zn-0.5Zr-0.6Nd alloy were achieved after annealing at 200℃,with an ultimate tensile strength of 287 MPa,a yield strength of 235 MPa,and an elongation of 26.1%.The numerous deformed microstructures,twins,and precipitated phases in the rolled alloy could impede the deformation at room temperature and increase the work hardening rate.After annealing,a decrease in the work hardening effect and an increase in the dynamic recovery effect were obtained due to the formation of fine equiaxed grains,and the increased volume fraction of precipitated phases,which significantly improved the elongation of the alloy.Additionally,the addition of Nd element could enhance the annealing recrystallization rate,reduce the Schmid factor difference between basal and prismatic slip systems,facilitate multi-system slip initiation and improve the alloy plasticity.

Features of sampling stream sediments of large river valleys under cryolithogenesis conditions in the Balygychan-Sugoy trough,North-East of Russia

Comprehensive research has been implemented to raise the efficiency of the geochemical survey of stream sediments(SSs)that formed under the cryolithogenesis conditions.The authors analysed the composition,structure and specific features of the formation of exogenous anomalous geochemical fields(AGFs)identified through SSs of large river valleys of IV order.In our case,these were the valleys of Maly Ken,Ken and Tap Rivers.These rivers are located in the central and southern parts of the Balygychan-Sugoy trough enclosed in the Magadan region,North-East of Russia.The authors proposed a new technique to sample loose alluvium of SSs in the large river valleys along the profiles.The profiles were located across the valleys.The AGFs of Au,Ag,Pb,Zn,Sn,Bi,Mo and W were studied.Correlations between elements have been established.These elements are the main indicator elements of Au-Ag,Ag-Pb,Sn-Ag,Mo-W and Sn-W mineralization occurring on the sites under study.The results obtained were compared with the results of geochemical surveys of SSs.It is concluded that the AGFs recognized along the profiles reflect the composition and structure of eroded and drained ore zones,uncover completely and precisely the pattern of element distribution in loose sediments of large water flows.The alluvium fraction<0.25 mm seems to be most significant in a practical sense,as it concentrated numerous ore elements.Sampling of this fraction in the river valleys of IV order does not cause any difficulty,for this kind of material is plentiful.The developed technique of alluvium sampling within large river valleys is efficient in searching for diverse mineralization at all stages of prognostic prospecting.It is applicable for geochemical survey of SSs performed at different scales both in the North-East of Russia,as well as other regions with similar climatic conditions,where the SSs are formed under the cryolithogenesis conditions.

Large language models in laparoscopic surgery: A transformative opportunity

This opinion paper explores the transformative potential of large language models(LLMs)in laparoscopic surgery and argues for their integration to enhance surgical education,decision support,reporting,and patient care.LLMs can revolutionize surgical education by providing personalized learning experiences and accelerating skill acquisition.Intelligent decision support systems powered by LLMs can assist surgeons in making complex decisions,optimizing surgical workflows,and improving patient outcomes.Moreover,LLMs can automate surgical reporting and generate personalized patient education materials,streamlining documentation and improving patient engagement.However,challenges such as data scarcity,surgical semantic capture,real-time inference,and integration with existing systems need to be addressed for successful LLM integration.The future of laparoscopic surgery lies in the seamless integration of LLMs,enabling autonomous robotic surgery,predictive surgical planning,intraoperative decision support,virtual surgical assistants,and continuous learning.By harnessing the power of LLMs,laparoscopic surgery can be transformed,empowering surgeons and ultimately benefiting patients.

The Turbulent Schmidt Number for Transient Contaminant Dispersion in a Large Ventilated Room Using a Realizable k-εModel

Buildings with large open spaces in which chemicals are handled are often exposed to the risk of explosions.Computational fluid dynamics is a useful and convenient way to investigate contaminant dispersion in such large spaces.The turbulent Schmidt number(Sc_(t))concept has typically been used in this regard,and most studies have adopted a default value.We studied the concentration distribution for sulfur hexafluoride(SF_(6))assuming different emission rates and considering the effect of Sc_(t).Then we examined the same problem for a light gas by assuming hydrogen gas(H_(2))as the contaminant.When SF_(6) was considered as the contaminant gas,a variation in the emission rate completely changed the concentration distribution.When the emission rate was low,the gravitational effect did not take place.For both low and high emission rates,an increase in S_(ct) accelerated the transport rate of SF_(6).In contrast,for H_(2) as the contaminant gas,a larger S_(ct) could induce a decrease in the H_(2) transport rate.

Design of a large momentum acceptance proton therapy gantry utilizing AG-CCT magnets

The application of superconducting(SC)technology enables magnets to excite strong fields with small footprints,which has great potential for miniaturizing proton therapy gantries.However,the slow ramping rate of SC magnets results in a low treatment efficiency compared with normal-conducting(NC)gantries.To address this problem,this study proposes a compact proton therapy gantry design with a large momentum acceptance utilizing alternating-gradient canted-cosine-theta(AG-CCT)SC magnets.In our design,a high-transmission degrader is mounted in the middle of the gantry,and the upstream beamline employs NC magnets with small apertures.Downstream of the degrader,large-bore AG-CCT magnets with strong alternating focusing gradients are set symmetrically as a local achromat,which realizes a momentum acceptance of 20%(or 40%in the energy domain).Therefore,only three magnetic working points are required to cover a treatment energy of 70-230 Me V.Owing to the large momentum acceptance,the proton beam after the degrader can be directly delivered to the isocenter without truncating its energy spectrum,which can significantly increase the treatment efficiency but causes severe dispersion effects during pencil beam scanning.Therefore,a compensation method was introduced by tuning the normal and skewed quadrupoles during the scanning process.As a result,the new gantry not only presents a remarkable reduction in the size and weight of the facility but also shows good potential for fast treatment.

Multi-blade rubbing characteristics of the shaft-disk-blade-casing system with large rotation

Blade rubbing faults cause detrimental impact on the operation of aeroengines. Most of the existing studies on blade rubbing in the shaft-disk-blade-casing(SDBC) system have overlooked the elastic deformation of the blade, while some only consider the whirl of the rotor, neglecting its spin. To address these limitations, this paper proposes a dynamic model with large rotation for the SDBC system. The model incorporates the spin and whirl of the rotor, enabling the realistic reproduction of multiblade rubbing faults. To verify the accuracy of the SDBC model with large rotation and demonstrate its capability to effectively consider the rotational effects such as the centrifugal stiffening and gyroscopic effects, the natural characteristics and dynamic responses of the proposed model are compared with those obtained from reported research and experimental results. Furthermore, the effects of the rotating speed, contact stiffness,and blade number on the dynamic characteristics of the SDBC system with multi-blade rubbing are investigated. The results indicate that the phase angle between the rotor deflection and the unbalance excitation force increases with the increasing rotating speed,which significantly influences the rubbing penetration of each blade. The natural frequency of the SDBC system with rubbing constrain can be observed in the acceleration response of the casing and the torsional response of the shaft, and the frequency is related to the contact stiffness. Moreover, the vibration amplitude increases significantly with the product of the blade number under rubbing, and the rotating frequency approaches the natural frequency of the SDBC system. The proposed model can provide valuable insight for the fault diagnosis of rubbing in bladed rotating machinery.