As a common practice,a large hydro-generator will operate in leading phase conditions to absorb the reactive power of the power grid.However,the accurate and precise prediction of the leading phase operation capacity ...As a common practice,a large hydro-generator will operate in leading phase conditions to absorb the reactive power of the power grid.However,the accurate and precise prediction of the leading phase operation capacity of a large hydro-generator has always been a formidable challenge to engineers and academicians because it is extremely hard to compute the eddy currents and losses as well as the local overheating in the pressure plate and finger.To address this problem,a full three dimensional(3D)finite element model and method of the coupled eddy current and temperature fields in the end region of a large hydro-generator are developed.The equivalent medium parameters used in the computations are comprehensively discussed.Moreover,some numerically based solution methodologies for accurate computation of the field and armature currents under different leading phase conditions are proposed.Numerical results on the coupled eddy current and temperature fields in the end regions of a 250 MW hydro-generator confirm positively the feasibility of the present work.展开更多
Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...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.展开更多
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 w...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.展开更多
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 p...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.展开更多
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...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.展开更多
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 h...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.展开更多
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 m...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.展开更多
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 ...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.展开更多
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 ord...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.展开更多
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 lar...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.展开更多
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 b...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.展开更多
Negative Poisson’s ratio(NPR)metamaterials are attractive for their unique mechanical behaviors and potential applications in deformation control and energy absorption.However,when subjected to significant stretching...Negative Poisson’s ratio(NPR)metamaterials are attractive for their unique mechanical behaviors and potential applications in deformation control and energy absorption.However,when subjected to significant stretching,NPR metamaterials designed under small strain assumption may experience a rapid degradation in NPR performance.To address this issue,this study aims to design metamaterials maintaining a targeted NPR under large deformation by taking advantage of the geometry nonlinearity mechanism.A representative periodic unit cell is modeled considering geometry nonlinearity,and its topology is designed using a gradient-free method.The unit cell microstructural topologies are described with the material-field series-expansion(MFSE)method.The MFSE method assumes spatial correlation of the material distribution,which greatly reduces the number of required design variables.To conveniently design metamaterials with desired NPR under large deformation,we propose a two-stage gradient-free metamaterial topology optimization method,which fully takes advantage of the dimension reduction benefits of the MFSE method and the Kriging surrogate model technique.Initially,we use homogenization to find a preliminary NPR design under a small deformation assumption.In the second stage,we begin with this preliminary design and minimize deviations in NPR from a targeted value under large deformation.Using this strategy and solution technique,we successfully obtain a group of NPR metamaterials that can sustain different desired NPRs in the range of[−0.8,−0.1]under uniaxial stretching up to 20% strain.Furthermore,typical microstructure designs are fabricated and tested through experiments.The experimental results show good consistency with our numerical results,demonstrating the effectiveness of the present gradientfree NPR metamaterial design strategy.展开更多
Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced ...Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.展开更多
In the process of constructing domain-specific knowledge graphs,the task of relational triple extraction plays a critical role in transforming unstructured text into structured information.Existing relational triple e...In the process of constructing domain-specific knowledge graphs,the task of relational triple extraction plays a critical role in transforming unstructured text into structured information.Existing relational triple extraction models facemultiple challenges when processing domain-specific data,including insufficient utilization of semantic interaction information between entities and relations,difficulties in handling challenging samples,and the scarcity of domain-specific datasets.To address these issues,our study introduces three innovative components:Relation semantic enhancement,data augmentation,and a voting strategy,all designed to significantly improve the model’s performance in tackling domain-specific relational triple extraction tasks.We first propose an innovative attention interaction module.This method significantly enhances the semantic interaction capabilities between entities and relations by integrating semantic information fromrelation labels.Second,we propose a voting strategy that effectively combines the strengths of large languagemodels(LLMs)and fine-tuned small pre-trained language models(SLMs)to reevaluate challenging samples,thereby improving the model’s adaptability in specific domains.Additionally,we explore the use of LLMs for data augmentation,aiming to generate domain-specific datasets to alleviate the scarcity of domain data.Experiments conducted on three domain-specific datasets demonstrate that our model outperforms existing comparative models in several aspects,with F1 scores exceeding the State of the Art models by 2%,1.6%,and 0.6%,respectively,validating the effectiveness and generalizability of our approach.展开更多
In order to improve rib stability,failure criteria and instability mode of a thick coal seam with inter-band rock layer are analysed in this study.A three-dimensional mechanical model is established for the rib by con...In order to improve rib stability,failure criteria and instability mode of a thick coal seam with inter-band rock layer are analysed in this study.A three-dimensional mechanical model is established for the rib by considering the rock layer.A safety factor is defined foy the rib,and it is observed that the safety factor exhibits a positive correlation with the thickness and strength of the inter-band rock.A calculation method for determining critical parameters of the rock layer is presented to ensure the rib stability.It is revealed that incomplete propagation of the fracture at the hard rock constitutes a fundamental prerequisite for ensuring the rib stability.The influence of the position of the inter-band rock in the coal seam on failure mechanism of the rib was thoroughly investigated by developing a series of physical models for the rib at the face area.The best position for the inter-band rock in the coal seam is at a height of 1.5 m away from the roof line,which tends to provide a good stability state for the rib.For different inter-band rock positions,two ways of controlling rib by increasing supports stiffness and flexible grouting reinforcement are proposed.展开更多
Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues...Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.展开更多
The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Infor...The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Information (PII) and other confidential or protected information that may have been memorized during training, specifically during a fine-tuning or customization process. We describe different black-box attacks from potential adversaries and study their impact on the amount and type of information that may be recovered from commonly used and deployed LLMs. Our research investigates the relationship between PII leakage, memorization, and factors such as model size, architecture, and the nature of attacks employed. The study utilizes two broad categories of attacks: PII leakage-focused attacks (auto-completion and extraction attacks) and memorization-focused attacks (various membership inference attacks). The findings from these investigations are quantified using an array of evaluative metrics, providing a detailed understanding of LLM vulnerabilities and the effectiveness of different attacks.展开更多
Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data o...Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data of 37 patients with large proximal ureteral stones more than 1.5 cm in diameter treated by prone npPCNL.Depending on stone size,in-toto stone removal or lithotripsy using the Lithoclast®Trilogy(EMS Medical,Nyon,Switzerland)was performed.Perioperative parameters including operative time(from start of puncture to the skin suturing),stone extraction time(from the first insertion of the nephroscope to the extraction of all stone fragments),and the stone-free rate were evaluated.Results:Twenty-one males and 16 females underwent npPCNL for the management of large upper ureteral calculi.The median age and stone size of treated patients were 58(interquartile range[IQR]:51-69)years and 19.3(IQR:18.0-22.0)mm,respectively.The median operative time and stone extraction time were 25(IQR:21-29)min and 8(IQR:7-10)min,respectively.One case(2.7%)of postoperative bleeding and two cases(5.4%)of prolonged fever were managed conservatively.The stone-free rate at a 1-month follow-up was 94.6%.Conclusion:The npPCNL provides a straight route to the ureteropelvic junction and proximal ureter.Approaching from a dilated portion of the ureter under low irrigation pressure with larger diameter instruments results in effective and safe stone extraction within a few minutes.展开更多
●AIM:To introduce the macular hole(MH)hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH.●METHODS:This retrospective observational case series comprised 16 consec...●AIM:To introduce the macular hole(MH)hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH.●METHODS:This retrospective observational case series comprised 16 consecutive patients(17 eyes)diagnosed with MH.Inclusion criteria involved a hole aperture diameter larger than 600μm or the presence of an unclosed MH larger than 600μm following the previous vitrectomy.Standard MH repair procedures were administered in all cases,involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle.A comprehensive assessment was conducted for each case before and after surgery,and optical coherence tomography(OCT)images were captured at every follow-up point.●RESULTS:The mean preoperative aperture diameter was 747±156μm(range 611-1180μm),with a mean base diameter of 1390±435μm(range 578-2220μm).Following surgery,all cases achieved complete anatomical closure of MH,with 13 cases(76.5%)exhibiting type 1 closure and 4 cases(23.5%)demonstrating type 2 closure.No significant differences were observed in the preoperative OCT variables between the two closure types.Eyes with type 1 closure showed a significantly improved visual acuity(0.70±0.10,range 0.50-0.80)compared to those with type 2 closure(0.90±0.12,range 0.80-1.00,P=0.014).●CONCLUSION:The MH hydromassage technique demonstrates promising results,achieving acceptable closure rates in cases of large or persistent MH.This technique may serve as an effective adjunctive maneuver during challenging MH surgery.展开更多
BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early...BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.展开更多
文摘As a common practice,a large hydro-generator will operate in leading phase conditions to absorb the reactive power of the power grid.However,the accurate and precise prediction of the leading phase operation capacity of a large hydro-generator has always been a formidable challenge to engineers and academicians because it is extremely hard to compute the eddy currents and losses as well as the local overheating in the pressure plate and finger.To address this problem,a full three dimensional(3D)finite element model and method of the coupled eddy current and temperature fields in the end region of a large hydro-generator are developed.The equivalent medium parameters used in the computations are comprehensively discussed.Moreover,some numerically based solution methodologies for accurate computation of the field and armature currents under different leading phase conditions are proposed.Numerical results on the coupled eddy current and temperature fields in the end regions of a 250 MW hydro-generator confirm positively the feasibility of the present work.
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘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.
基金supported by the National Natural Science Foundation of China (Grant Nos. 92158204, 41506001 and 42076019)a Project supported by the Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (Grant No. 311021005)。
文摘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.
基金supported by the National Science and Technology Innovation 2030 Major Projects(2021ZD0202200)National Natural Science Foundation of China(32171090,81970264)+1 种基金Shanghai Science and Technology Commission(21ZR1482600)2023 Youth Innovation Promotion Association CAS。
文摘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.
基金Supported by National Natural Science Foundation of China(Grant No.52005371)Shanghai Pujiang Program of China(Grant No.2020PJD071)+1 种基金Shanghai Municipal Natural Science Foundation of China(Grant No.22ZR1463900)Fundamental Research Funds for the Central Universities of China.
文摘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.
基金the National Key R&D Program of China(Grant No.2021YFC3000802)the National Natural Science Foundation of China(Grant No.42175165)the National Key Scientific and Technological Infrastructure project“Earth System Numerical Simulation Facility”(EarthLab).
文摘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.
基金Project supported by the Natural Science Foundation of Jiangsu Province (Grant No.BK20220917)the National Natural Science Foundation of China (Grant Nos.12001213 and 12302035)。
文摘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.
基金supported by Natural Science Foundation of Fujian Province (CN) (2020I0009, 2022J01596)Cooperation Project on University Industry-Education-Research of Fujian Provincial Science and Technology Plan (CN) (2022N5011)+1 种基金Lancang-Mekong Cooperation Special Fund (2017-2020)International Sci-Tech Cooperation and Communication Program of Fujian Agriculture and Forestry University (KXGH17014)。
文摘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.
基金partially supported by the National Nature Science Foundation of China(12271114)the Guangxi Natural Science Foundation(2023JJD110009,2019JJG110003,2019AC20214)+2 种基金the Innovation Project of Guangxi Graduate Education(JGY2023061)the Key Laboratory of Mathematical Model and Application(Guangxi Normal University)the Education Department of Guangxi Zhuang Autonomous Region。
文摘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.
基金funded by the National Natural Science Foundation of China and the Machinery Industry Innovation Platform Construction Project of China Machinery Industry Federation,Grant Numbers 52378103 and 2019SA-10-07.
文摘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.
基金Project supported by the National Science and Technology Major Project of China (No. 2017-V-0009)the National Natural Science Foundation of China (Nos. 12032015 and 12121002)the National Funding Program for Postdoctoral Researchers of China (No. GZC20231586)。
文摘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.
基金the support of the National Science Foundation of China(12372120,12172075)the Liaoning Revitalization Talents Program(XLYC2007027)Fundamental Research Funds for the Central Universities(DUT21RC(3)067).
文摘Negative Poisson’s ratio(NPR)metamaterials are attractive for their unique mechanical behaviors and potential applications in deformation control and energy absorption.However,when subjected to significant stretching,NPR metamaterials designed under small strain assumption may experience a rapid degradation in NPR performance.To address this issue,this study aims to design metamaterials maintaining a targeted NPR under large deformation by taking advantage of the geometry nonlinearity mechanism.A representative periodic unit cell is modeled considering geometry nonlinearity,and its topology is designed using a gradient-free method.The unit cell microstructural topologies are described with the material-field series-expansion(MFSE)method.The MFSE method assumes spatial correlation of the material distribution,which greatly reduces the number of required design variables.To conveniently design metamaterials with desired NPR under large deformation,we propose a two-stage gradient-free metamaterial topology optimization method,which fully takes advantage of the dimension reduction benefits of the MFSE method and the Kriging surrogate model technique.Initially,we use homogenization to find a preliminary NPR design under a small deformation assumption.In the second stage,we begin with this preliminary design and minimize deviations in NPR from a targeted value under large deformation.Using this strategy and solution technique,we successfully obtain a group of NPR metamaterials that can sustain different desired NPRs in the range of[−0.8,−0.1]under uniaxial stretching up to 20% strain.Furthermore,typical microstructure designs are fabricated and tested through experiments.The experimental results show good consistency with our numerical results,demonstrating the effectiveness of the present gradientfree NPR metamaterial design strategy.
文摘Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.
基金Science and Technology Innovation 2030-Major Project of“New Generation Artificial Intelligence”granted by Ministry of Science and Technology,Grant Number 2020AAA0109300.
文摘In the process of constructing domain-specific knowledge graphs,the task of relational triple extraction plays a critical role in transforming unstructured text into structured information.Existing relational triple extraction models facemultiple challenges when processing domain-specific data,including insufficient utilization of semantic interaction information between entities and relations,difficulties in handling challenging samples,and the scarcity of domain-specific datasets.To address these issues,our study introduces three innovative components:Relation semantic enhancement,data augmentation,and a voting strategy,all designed to significantly improve the model’s performance in tackling domain-specific relational triple extraction tasks.We first propose an innovative attention interaction module.This method significantly enhances the semantic interaction capabilities between entities and relations by integrating semantic information fromrelation labels.Second,we propose a voting strategy that effectively combines the strengths of large languagemodels(LLMs)and fine-tuned small pre-trained language models(SLMs)to reevaluate challenging samples,thereby improving the model’s adaptability in specific domains.Additionally,we explore the use of LLMs for data augmentation,aiming to generate domain-specific datasets to alleviate the scarcity of domain data.Experiments conducted on three domain-specific datasets demonstrate that our model outperforms existing comparative models in several aspects,with F1 scores exceeding the State of the Art models by 2%,1.6%,and 0.6%,respectively,validating the effectiveness and generalizability of our approach.
基金financial support from the National Key Research and Development Program of China (No.2023YFC2907501)the National Natural Science Foundation of China (No.52374106)the Fundamental Research Funds for the Central Universities (No.2023ZKPYNY01)。
文摘In order to improve rib stability,failure criteria and instability mode of a thick coal seam with inter-band rock layer are analysed in this study.A three-dimensional mechanical model is established for the rib by considering the rock layer.A safety factor is defined foy the rib,and it is observed that the safety factor exhibits a positive correlation with the thickness and strength of the inter-band rock.A calculation method for determining critical parameters of the rock layer is presented to ensure the rib stability.It is revealed that incomplete propagation of the fracture at the hard rock constitutes a fundamental prerequisite for ensuring the rib stability.The influence of the position of the inter-band rock in the coal seam on failure mechanism of the rib was thoroughly investigated by developing a series of physical models for the rib at the face area.The best position for the inter-band rock in the coal seam is at a height of 1.5 m away from the roof line,which tends to provide a good stability state for the rib.For different inter-band rock positions,two ways of controlling rib by increasing supports stiffness and flexible grouting reinforcement are proposed.
基金funded by Hainan Provincial Natural Science Foundation of China(820QN401,822QN468)Science and Technology Special Fund of Hainan Province,China,(ZDYF2024SHFZ114)+1 种基金Health Science and Technology Innovation Joint Project of Hainan Province,China(WSJK2024MS231)Hainan Province Clinical Medical Center Construction(Project[2022]276).
文摘Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.
文摘The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Information (PII) and other confidential or protected information that may have been memorized during training, specifically during a fine-tuning or customization process. We describe different black-box attacks from potential adversaries and study their impact on the amount and type of information that may be recovered from commonly used and deployed LLMs. Our research investigates the relationship between PII leakage, memorization, and factors such as model size, architecture, and the nature of attacks employed. The study utilizes two broad categories of attacks: PII leakage-focused attacks (auto-completion and extraction attacks) and memorization-focused attacks (various membership inference attacks). The findings from these investigations are quantified using an array of evaluative metrics, providing a detailed understanding of LLM vulnerabilities and the effectiveness of different attacks.
文摘Objective:To evaluate the feasibility and the safety of medial non-papillary percutaneous nephrolithotomy(npPCNL)for the management of large proximal ureteral stones.Methods:We evaluated prospectively collected data of 37 patients with large proximal ureteral stones more than 1.5 cm in diameter treated by prone npPCNL.Depending on stone size,in-toto stone removal or lithotripsy using the Lithoclast®Trilogy(EMS Medical,Nyon,Switzerland)was performed.Perioperative parameters including operative time(from start of puncture to the skin suturing),stone extraction time(from the first insertion of the nephroscope to the extraction of all stone fragments),and the stone-free rate were evaluated.Results:Twenty-one males and 16 females underwent npPCNL for the management of large upper ureteral calculi.The median age and stone size of treated patients were 58(interquartile range[IQR]:51-69)years and 19.3(IQR:18.0-22.0)mm,respectively.The median operative time and stone extraction time were 25(IQR:21-29)min and 8(IQR:7-10)min,respectively.One case(2.7%)of postoperative bleeding and two cases(5.4%)of prolonged fever were managed conservatively.The stone-free rate at a 1-month follow-up was 94.6%.Conclusion:The npPCNL provides a straight route to the ureteropelvic junction and proximal ureter.Approaching from a dilated portion of the ureter under low irrigation pressure with larger diameter instruments results in effective and safe stone extraction within a few minutes.
基金Supported by National Natural Science Foundation of China(NSFC)fund(No.81970815).
文摘●AIM:To introduce the macular hole(MH)hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH.●METHODS:This retrospective observational case series comprised 16 consecutive patients(17 eyes)diagnosed with MH.Inclusion criteria involved a hole aperture diameter larger than 600μm or the presence of an unclosed MH larger than 600μm following the previous vitrectomy.Standard MH repair procedures were administered in all cases,involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle.A comprehensive assessment was conducted for each case before and after surgery,and optical coherence tomography(OCT)images were captured at every follow-up point.●RESULTS:The mean preoperative aperture diameter was 747±156μm(range 611-1180μm),with a mean base diameter of 1390±435μm(range 578-2220μm).Following surgery,all cases achieved complete anatomical closure of MH,with 13 cases(76.5%)exhibiting type 1 closure and 4 cases(23.5%)demonstrating type 2 closure.No significant differences were observed in the preoperative OCT variables between the two closure types.Eyes with type 1 closure showed a significantly improved visual acuity(0.70±0.10,range 0.50-0.80)compared to those with type 2 closure(0.90±0.12,range 0.80-1.00,P=0.014).●CONCLUSION:The MH hydromassage technique demonstrates promising results,achieving acceptable closure rates in cases of large or persistent MH.This technique may serve as an effective adjunctive maneuver during challenging MH surgery.
文摘BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.