This paper investigates the influence of the spanwise-distributed trailing-edge camber morphing on the dynamic stall characteristics of a finite-span wing at Re=2×10^(5).The mathematical model of the spanwise-dis...This paper investigates the influence of the spanwise-distributed trailing-edge camber morphing on the dynamic stall characteristics of a finite-span wing at Re=2×10^(5).The mathematical model of the spanwise-distributed trailing-edge camber morphing is established based on Chebyshev polynomials,and the deformed wing surface is modeled by a spline surface according to the rib's morphing in the chordwise direction.The Computational Fluid Dynamics(CFD)method is adopted to obtain flow-field results and aerodynamic forces.The SST-γmodel is introduced and the overset mesh technique is adopted.The numerical results show that the spanwisedistributed trailing-edge morphing obviously changes the aerodynamic and energy transfer characteristics of the dynamic stall.Especially when the phase difference between the trailing-edge motion and the wing pitch is-π/2,the interaction between the three-dimensional(3-D)Leading-Edge Vortex(LEV)and Trailing-Edge Vortex(TEV)is strengthened,and the work done by the aerodynamic force turns negative.This indicates that the trailing-edge deformation has the potential to suppress the oscillation amplitude of stall flutter.We also found that as the trailing-edge camber morphing varies more complexly along the spanwise direction,the suppression effect decreases accordingly.展开更多
An efficient,diversified,and low-dimensional airfoil parameterization method is critical to airfoil aerodynamic optimization design.This paper proposes a supersonic airfoil parameterization method based on a bijective...An efficient,diversified,and low-dimensional airfoil parameterization method is critical to airfoil aerodynamic optimization design.This paper proposes a supersonic airfoil parameterization method based on a bijective cycle generative adversarial network(Bicycle-GAN),whose performance is compared with that of the conditional variational autoencoder(cVAE)based parameterization method in terms of parsimony,flawlessness,intuitiveness,and physicality.In all four aspects,the Bicycle-GAN-based parameterization method is superior to the cVAEbased parameterization method.Combined with multifidelity Gaussian process regression(MFGPR)surrogate model and a Bayesian optimization algorithm,a Bicycle-GAN-based optimization framework is established for the aerodynamic performance optimization of airfoils immersed in supersonic flow,which is compared with the cVAE-based optimization method in terms of optimized efficiency and effectiveness.The MFGPR surrogate model is established using low-fidelity aerodynamic data obtained from supersonic thin-airfoil theory and high-fidelity aerodynamic data obtained from steady CFD simulation.For both supersonic conditions,the CFD simulation costs are reduced by>20%compared with those of the cVAE-based optimization,and better optimization results are obtained through the Bicycle-GAN model.The optimization results for this supersonic flow point to a sharper leading edge,a smaller camber and thickness with a flatter lower surface,and a maximum thickness at 50%chord length.The advantages of the Bicycle-GAN and MFGPR models are comprehensively demonstrated in terms of airfoil generation characteristics,surrogate model prediction accuracy and optimization efficiency.展开更多
During high-speed forward flight,helicopter rotor blades operate across a wide range of Reynolds and Mach numbers.Under such conditions,their aerodynamic performance is significantly influenced by dynamic stall—a com...During high-speed forward flight,helicopter rotor blades operate across a wide range of Reynolds and Mach numbers.Under such conditions,their aerodynamic performance is significantly influenced by dynamic stall—a complex,unsteady flow phenomenon highly sensitive to inlet conditions such asMach and Reynolds numbers.The key features of three-dimensional blade stall can be effectively represented by the dynamic stall behavior of a pitching airfoil.In this study,we conduct an uncertainty quantification analysis of dynamic stall aerodynamics in high-Mach-number flows over pitching airfoils,accounting for uncertainties in inlet parameters.A computational fluid dynamics(CFD)model based on the compressible unsteady Reynolds-averagedNavier–Stokes(URANS)equations,coupledwith sliding mesh techniques,is developed to simulate the unsteady aerodynamic behavior and associated flow fields.To efficiently capture the aerodynamic responses while maintaining high accuracy,a multi-fidelity Co-Kriging surrogate model is constructed.This model integrates the precision of high-fidelity wind tunnel experiments with the computational efficiency of lower-fidelity URANS simulations.Its accuracy is validated through direct comparison with experimental data.Building upon this surrogate model,we employ interval analysis and the Sobol sensitivity method to quantify the uncertainty and parameter sensitivity of the unsteady aerodynamic forces resulting frominlet condition variability.Both the inlet Mach number and Reynolds number are treated as uncertain inputs,modeled using interval representations.Our results demonstrate that variations inMach number contribute far more significantly to aerodynamic uncertainty than those in Reynolds number.Moreover,the presence of dynamic stall vortices markedly amplifies the aerodynamic sensitivity to Mach number fluctuations.展开更多
In this paper,a series of flutter simulations are carried out to investigate the effects of split drag rudder(SDR)on the transonic flutter characteristic of rigid NACA 64A010.A structural dynamic model addressing two-...In this paper,a series of flutter simulations are carried out to investigate the effects of split drag rudder(SDR)on the transonic flutter characteristic of rigid NACA 64A010.A structural dynamic model addressing two-degree-of-freedom pitch-plunge aeroelastic oscillations was coupled with the unsteady Reynolds-averaged Navier-Stokes equations to perform flutter simulation.Meanwhile,the influence mechanism of SDR on flutter boundary is explained through aerodynamic work and the correlated shock wave location.The results show that the SDR delays the shock wave shifting downstream,and the Mach number corresponding to reaching freeze region increases as the split angle increases.Therefore,the peak value of aerodynamic moment coefficient amplitude and the sharp ascent process of phase occurs at higher Mach number,which leads to the delay in the occurrence of the transonic dip.Besides,before the transonic dip of airfoil without SDR occurs,the aerodynamic moment phase of airfoil with the SDR decreases slowly due to the decrease in the speed of shock wave moving downstream.This results in an increased flutter speed when employing the SDR before the transonic dip of airfoil without SDR occurs.Meanwhile,the effects of asymmetric split angles on the transonic flutter characteristics are also investigated.Before the transonic dip of airfoil without SDR occurs,the flutter characteristic is dominated by the smaller split angle.展开更多
A sub-rapidly solidified LaFe11.6Si1.4 plate was fabricated directly from liquid by centrifugal casting method. The phase constitution, microstructure and magnetocaloric effect were investigated using backscatter scan...A sub-rapidly solidified LaFe11.6Si1.4 plate was fabricated directly from liquid by centrifugal casting method. The phase constitution, microstructure and magnetocaloric effect were investigated using backscatter scanning electron microscopy, X-ray diffraction, differential scanning calorimetry and phys- ical property measurement system. When the plate was annealed at 1373 K, rl phase was formed by a solid-state peritectoid reaction. A first-order magnetic phase transition occurred in the vicinity of 188 K, and the effective refrigeration capacities reached 203.5J/kg and 209.7J/kg in plates annealed for I h and 3 h, respectively, under a magnetic field change of 3T. It is suggested that centrifugal casting may become a new approach to prepare high-performance La-Fe-Si magnetocaloric plates for prac- tical applications, which could largely accelerate the formation of rl phase during high-temperature heat-treatment process due to refined and homogeneous honeycombed microstructure.展开更多
A flight dynamics model based on elastic blades for helicopters is developed.Modal shape analysis is used to describe the rotating elastic blades for the purpose of reducing the elastic degrees of freedom for blades.T...A flight dynamics model based on elastic blades for helicopters is developed.Modal shape analysis is used to describe the rotating elastic blades for the purpose of reducing the elastic degrees of freedom for blades.The analytical result is employed to predict the rotor forces and moments.The equilibrium equation of the flight dynamics model is then constructed for the elastic motion for blades and the rigid motion for other parts.The nonlinear equation is further simplified,and the gradient descent algorithm is adopted to implement the trim simulation.The trim analysis shows that the effect of blade elasticity on the accuracy of rotor forces and moments is apparent at high speed,and the proposed method presents good accuracy for trim performance.The timedomain response is realized by a combination of the Newmark method and the adaptive RungeKutta method.The helicopter control responses of collective pitch show that the response accuracy of the model at a yaw-and-pitch attitude is improved.Finally,the influence of blade elasticity on the helicopter dynamic response in low-altitude wind shear is investigated.An increase in blade elasticity reduces the oscillation amplitude of the yaw angle and the vertical speed by more than 70%.Compared with a rigid blade,an elastic blade reduces the vibration frequency of the angular velocity and results in a fast return of the helicopter to its stable flight.展开更多
The modeling of dynamic stall aerodynamics is essential to stall flutter, due to the flow separation in a large-amplitude pitching oscillation process. A newly neural network based Reduced Order Model(ROM) framework f...The modeling of dynamic stall aerodynamics is essential to stall flutter, due to the flow separation in a large-amplitude pitching oscillation process. A newly neural network based Reduced Order Model(ROM) framework for predicting the aerodynamic forces of an airfoil undergoing large-amplitude pitching oscillation at various velocities is presented in this work. First, the dynamic stall aerodynamics is calculated by solving RANS equations and the transitional SST-γ model. Afterwards, the stall flutter bifurcation behavior is calculated by the above CFD solver coupled with structural dynamic equation. The critical flutter speed and limit-cycle oscillation amplitudes are consistent with those obtained by experiments. A newly multi-layer Gated Recurrent Unit(GRU) neural network based ROM is constructed to accelerate the calculation of aerodynamic forces. The training and validation process are carried out upon the unsteady aerodynamic data obtained by the proposed CFD method. The well-trained ROM is then coupled with the structure equation at a specific velocity, the Limit-Cycle Oscillation(LCO) of stall flutter under this flow condition is predicted precisely and more quickly. In order to predict both the critical flutter velocity and LCO amplitudes after bifurcation at different velocities, a new ROM with GRU neural network considering the variation of flow velocities is developed. The stall flutter results predicted by ROM agree well with the CFD ones at different velocities. Finally, a brief sensitivity analysis of two structural parameters of ROM is carried out. It infers the potential of the presented modeling method to depict the nonlinearity of dynamic stall and stall flutter phenomenon.展开更多
This paper focuses on the effect of the phase offset of Leading-Edge(LE)morphing on the aerodynamic characteristics of a pitching NACA0012 airfoil.Assuming an unstretched camber and using polynomial interpolation,an e...This paper focuses on the effect of the phase offset of Leading-Edge(LE)morphing on the aerodynamic characteristics of a pitching NACA0012 airfoil.Assuming an unstretched camber and using polynomial interpolation,an explicit expression for LE nonlinear morphing is proposed and implemented for the large pitching motion of the airfoil.Flow field results and aerodynamic forces are obtained by solving the unsteady Reynolds-averaged Navier-Stokes equations for both the airfoil’s pitching motion and LE morphing.Furthermore,the index of instantaneous aerodynamic power is used to quantify the work done by the airflow in a dynamic process.According to the instantaneous aerodynamic power and energy map,which denotes the energy transfer between the airfoil’s oscillation and flow field,the airfoil is subject to stall flutter.The results show that LE morphing with an optimal phase offset of 315°reduces the energy extraction from the flow field,suppressing the stall flutter instability.This optimal phase offset is effective at different pitching axis positions of the airfoil.The results signify that LE morphing can suppress stall flutter by advancing the occurrence of the first LE vortex and increasing the nose-down moment during the upstroke period.展开更多
Precise mapping of leukemic cells onto the known hematopoietic hierarchy is important for understanding the cell-of-origin and mechanisms underlying disease initiation and development.However,this task remains challen...Precise mapping of leukemic cells onto the known hematopoietic hierarchy is important for understanding the cell-of-origin and mechanisms underlying disease initiation and development.However,this task remains challenging because of the high interpatient and intrapatient heterogeneity of leukemia cell clones as well as the differences that exist between leukemic and normal hematopoietic cells.Using single-cell RNA sequencing(scRNA-seq)data with a curated clustering approach,we constructed a comprehensive reference hierarchy of normal hematopoiesis.This reference hierarchy was accomplished through multistep clustering and annotating over 100,000 bone marrow mononuclear cells derived from 25 healthy donors.We further employed the cosine distance algorithm to develop a likelihood score to determine the similarities of leukemic cells to their putative normal counterparts.Using our scoring strategies,we mapped the cells of acute myeloid leukemia(AML)and B cell precursor acute lymphoblastic leukemia(BCP-ALL)samples to their corresponding counterparts.The reference hierarchy also facilitated bulk RNA sequencing(RNA-seq)analysis,enabling the development of a least absolute shrinkage and selection operator(LASSO)score model to reveal subtle differences in lineage aberrancy within AML or BCP-ALL patients.To facilitate interpretation and application,we established an R-based package(HematoMap)that offers a fast,convenient,and user-friendly tool for identifying and visualizing lineage aberrations in leukemia from scRNA-seq and bulk RNA-seq data.Our tool provides curated resources and data analytics for understanding leukemogenesis,with the potential to enhance leukemia risk stratification and personalized treatments.The HematoMap is available at https://github.com/NRCTM-bioinfo/HematoMap.展开更多
B-cell precursor acute lymphoblastic leukemia(BCP-ALL)is characterized by genetic alterations with high heterogeneity.Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed ...B-cell precursor acute lymphoblastic leukemia(BCP-ALL)is characterized by genetic alterations with high heterogeneity.Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology.Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes,such as DUX4 rearrangements,MEF2D rearrangements,ZNF384/ZNF362 rearrangements,NUTM1 rearrangements,BCL2/MYC and/or BCL6 rearrangements,ETV6-RUNX1-like gene expression,PAX5alt(diverse PAX5 alterations,including rearrangements,intragenic amplifications,or mutations),and hotspot mutations PAX5(p.Pro80Arg)with biallelic PAX5 alterations,IKZF1(p.Asn159Tyr),and ZEB2(p.His1038Arg).These molecular subtypes could be classified by gene expression patterns with RNA-seq technology.Refined molecular classification greatly improved the treatment strategy.Multiagent therapy regimens,including target inhibitors(e.g.,imatinib),immunomodulators,monoclonal antibodies,and chimeric antigen receptor T-cell(CAR-T)therapy,are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management.We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.展开更多
T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modificatio...T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modifications,such as ubiquitination,regulate NOTCH1 stability,activity,and localization.However,the specific deubiquitinase that affects NOTCH1 protein stability remains unestablished.Here,we report that ubiquitin-specific protease 7(USP7)can stabilize NOTCH1.USP7 deubiquitinated NOTCH1 in vivo and in vitro,whereas knockdown of USP7 increased the ubiquitination of NOTCH1.USP7 interacted with NOTCH1 protein in T-ALL cells,and the MATH and UBL domains of USP7 were responsible for this interaction.Depletion of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo,accompanied by downregulation of the NOTCH1 protein level.Similarly,pharmacologic inhibition of USP7 led to apoptosis of T-ALL cells.More importantly,we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples,and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells,indicating the clinical relevance of these findings.Overall,our results demonstrate that USP7 is a novel deubiquitinase that stabilizes NOTCH1.Therefore,USP7 may be a promising therapeutic target in the currently incurable T-ALL.展开更多
OriginalTranslation t(8;21)(q22;q22)acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy with a high relapse rate in China.Two leukemic myeloblast populations(CD34^(+)CD117^(dim) and CD34^(+)C...OriginalTranslation t(8;21)(q22;q22)acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy with a high relapse rate in China.Two leukemic myeloblast populations(CD34^(+)CD117^(dim) and CD34^(+)CD117^(bri))were previously identified in t(8;21)AML,and CD34^(+)CD117^(dim) cell proportion was determined as an independent factor for this disease outcome.Here,we examined the impact of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression on t(8;21)AML clinical prognosis.In this study,85 patients with t(8;21)AML were enrolled.The mRNA expression levels of CD34^(+)CD117^(dim)-associated genes(LGALS1,EMP3,and CRIP1)and CD34^(+)CD117^(bri)-associated genes(TRH,PLAC8,and IGLL1)were measured using quantitative reverse transcription PCR.Associations between gene expression and clinical outcomes were determined using Cox regression models.Results showed that patients with high LGALS1,EMP3,or CRIP1 expression had significantly inferior overall survival(OS),whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis.Univariate analysis revealed that CD19,CD34^(+)CD117^(dim) proportion,KIT mutation,minimal residual disease(MRD),and expression levels of LGALS1,EMP3,CRIP1,TRH and PLAC8 were associated with OS.Multivariate analysis indicated that KIT mutation,MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS.Identifying the clinical relevance of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21)AML.展开更多
More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane associ...More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.展开更多
Pituitary neuroendocrine tumors(PitNETs)are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis,yet their regulatory effects on peripheral immune ne...Pituitary neuroendocrine tumors(PitNETs)are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis,yet their regulatory effects on peripheral immune networks remain poorly characterized.Here,we systematically analyzed bulk RNA sequencing(RNA‑seq)from 883 PitNET tumors,108 PitNET‑associated peripheral blood mononuclear cells(PBMC)samples,and 175 healthy PBMC controls,combined with 69 single‑cell RNA sequencing(scRNA-seq)samples covering tumors,normal pituitaries,as well as tumor‑derived and normal PBMCs.We identified a systemic immune disequilibrium in PitNET patients,characterized by increased circulating lymphocyte proportions,accompanied by upregulated cytokine-receptor interaction signatures.Notably,tumor resection reversed this imbalance,as supported by the normalization of monocyte and neutrophil counts,validated by flow cytometry and routine blood data from 600 samples(200 healthy controls and 200 PitNET patients with paired pre-and post-surgery follow‑up).Trajectory analysis identified terminally differentiated,secretory-specialized cell populations with lineage-specific hormone and cytokine hypersecretion.Ligand-receptor inference suggested these tumor-derived factors potentially engage circulating immune cell receptors.A random‑forest classifier based on PBMC transcriptomes distinguished PitNET subtypes,underscoring the diagnostic potential of peripheral immune signatures.Furthermore,in an estrogen-induced rat model,elevated PRL level coincided with the same peripheral immune skewing.Overall,our work provides a valuable resource and demonstrates PitNETs can be systemic immune modulators,where intrinsic hormone secretory activity and monocyte-lymphocyte imbalance collectively drive peripheral immune dysfunction.展开更多
Chimeric antigen receptor T-cell(CAR-T)therapy has been successfully applied in clinical treatment,especially for hematologic malignancies such as multiple myeloma(MM),but its broad application is limited by cytokine ...Chimeric antigen receptor T-cell(CAR-T)therapy has been successfully applied in clinical treatment,especially for hematologic malignancies such as multiple myeloma(MM),but its broad application is limited by cytokine release syndrome(CRS),a potentially life-threatening complication.Although metabolic alterations are known to accompany CRS,predictive biomarkers for its onset,severity,and associated metabolic remodeling remain unknown,hindering proactive clinical management.Here,we analyzed longitudinal serum metabolic profiles from 19 patients with relapsed/refractory MM receiving CAR-T therapy,with validation in an independent cohort of 23 patients.We observed dysregulated arginine metabolism that progressed alongside clinical CRS.At pre-lymphodepletion(Day–5),over half of differentially abundant metabolites were enriched in unsaturated fatty acid(UFA)synthesis pathways,which were exclusively upregulated in patients who later developed severe CRS.Furthermore,two lysophosphatidylcholines,namely,lysoPC(16:0)and lysoPC(15:0),were significantly associated with delayed CRS onset,with elevated concentrations correlated with a prolonged time to onset;this association was independently validated.These findings revealed that arginine metabolism was a pathological axis in CRS,UFAs were severity predictors,and specific lysoPCs were modulators of onset time.Collectively,they provide proactive CRS management,addressing critical gaps in predictive biomarkers to advance the safe,broad CAR-T application in MM.展开更多
基金co-supported by the National Natural Science Foundation of China(No.12472332)。
文摘This paper investigates the influence of the spanwise-distributed trailing-edge camber morphing on the dynamic stall characteristics of a finite-span wing at Re=2×10^(5).The mathematical model of the spanwise-distributed trailing-edge camber morphing is established based on Chebyshev polynomials,and the deformed wing surface is modeled by a spline surface according to the rib's morphing in the chordwise direction.The Computational Fluid Dynamics(CFD)method is adopted to obtain flow-field results and aerodynamic forces.The SST-γmodel is introduced and the overset mesh technique is adopted.The numerical results show that the spanwisedistributed trailing-edge morphing obviously changes the aerodynamic and energy transfer characteristics of the dynamic stall.Especially when the phase difference between the trailing-edge motion and the wing pitch is-π/2,the interaction between the three-dimensional(3-D)Leading-Edge Vortex(LEV)and Trailing-Edge Vortex(TEV)is strengthened,and the work done by the aerodynamic force turns negative.This indicates that the trailing-edge deformation has the potential to suppress the oscillation amplitude of stall flutter.We also found that as the trailing-edge camber morphing varies more complexly along the spanwise direction,the suppression effect decreases accordingly.
基金supported by the National Natural Science Founda-tion of China(Grant No 12302226)the China Postdoctoral Science Foundation(Grant No BX20230453).
文摘An efficient,diversified,and low-dimensional airfoil parameterization method is critical to airfoil aerodynamic optimization design.This paper proposes a supersonic airfoil parameterization method based on a bijective cycle generative adversarial network(Bicycle-GAN),whose performance is compared with that of the conditional variational autoencoder(cVAE)based parameterization method in terms of parsimony,flawlessness,intuitiveness,and physicality.In all four aspects,the Bicycle-GAN-based parameterization method is superior to the cVAEbased parameterization method.Combined with multifidelity Gaussian process regression(MFGPR)surrogate model and a Bayesian optimization algorithm,a Bicycle-GAN-based optimization framework is established for the aerodynamic performance optimization of airfoils immersed in supersonic flow,which is compared with the cVAE-based optimization method in terms of optimized efficiency and effectiveness.The MFGPR surrogate model is established using low-fidelity aerodynamic data obtained from supersonic thin-airfoil theory and high-fidelity aerodynamic data obtained from steady CFD simulation.For both supersonic conditions,the CFD simulation costs are reduced by>20%compared with those of the cVAE-based optimization,and better optimization results are obtained through the Bicycle-GAN model.The optimization results for this supersonic flow point to a sharper leading edge,a smaller camber and thickness with a flatter lower surface,and a maximum thickness at 50%chord length.The advantages of the Bicycle-GAN and MFGPR models are comprehensively demonstrated in terms of airfoil generation characteristics,surrogate model prediction accuracy and optimization efficiency.
文摘During high-speed forward flight,helicopter rotor blades operate across a wide range of Reynolds and Mach numbers.Under such conditions,their aerodynamic performance is significantly influenced by dynamic stall—a complex,unsteady flow phenomenon highly sensitive to inlet conditions such asMach and Reynolds numbers.The key features of three-dimensional blade stall can be effectively represented by the dynamic stall behavior of a pitching airfoil.In this study,we conduct an uncertainty quantification analysis of dynamic stall aerodynamics in high-Mach-number flows over pitching airfoils,accounting for uncertainties in inlet parameters.A computational fluid dynamics(CFD)model based on the compressible unsteady Reynolds-averagedNavier–Stokes(URANS)equations,coupledwith sliding mesh techniques,is developed to simulate the unsteady aerodynamic behavior and associated flow fields.To efficiently capture the aerodynamic responses while maintaining high accuracy,a multi-fidelity Co-Kriging surrogate model is constructed.This model integrates the precision of high-fidelity wind tunnel experiments with the computational efficiency of lower-fidelity URANS simulations.Its accuracy is validated through direct comparison with experimental data.Building upon this surrogate model,we employ interval analysis and the Sobol sensitivity method to quantify the uncertainty and parameter sensitivity of the unsteady aerodynamic forces resulting frominlet condition variability.Both the inlet Mach number and Reynolds number are treated as uncertain inputs,modeled using interval representations.Our results demonstrate that variations inMach number contribute far more significantly to aerodynamic uncertainty than those in Reynolds number.Moreover,the presence of dynamic stall vortices markedly amplifies the aerodynamic sensitivity to Mach number fluctuations.
文摘In this paper,a series of flutter simulations are carried out to investigate the effects of split drag rudder(SDR)on the transonic flutter characteristic of rigid NACA 64A010.A structural dynamic model addressing two-degree-of-freedom pitch-plunge aeroelastic oscillations was coupled with the unsteady Reynolds-averaged Navier-Stokes equations to perform flutter simulation.Meanwhile,the influence mechanism of SDR on flutter boundary is explained through aerodynamic work and the correlated shock wave location.The results show that the SDR delays the shock wave shifting downstream,and the Mach number corresponding to reaching freeze region increases as the split angle increases.Therefore,the peak value of aerodynamic moment coefficient amplitude and the sharp ascent process of phase occurs at higher Mach number,which leads to the delay in the occurrence of the transonic dip.Besides,before the transonic dip of airfoil without SDR occurs,the aerodynamic moment phase of airfoil with the SDR decreases slowly due to the decrease in the speed of shock wave moving downstream.This results in an increased flutter speed when employing the SDR before the transonic dip of airfoil without SDR occurs.Meanwhile,the effects of asymmetric split angles on the transonic flutter characteristics are also investigated.Before the transonic dip of airfoil without SDR occurs,the flutter characteristic is dominated by the smaller split angle.
基金financially supported by the National Natural Science Foundation of China(No.51474144)the Shanghai Sailing Program(No.17YF1405900)
文摘A sub-rapidly solidified LaFe11.6Si1.4 plate was fabricated directly from liquid by centrifugal casting method. The phase constitution, microstructure and magnetocaloric effect were investigated using backscatter scanning electron microscopy, X-ray diffraction, differential scanning calorimetry and phys- ical property measurement system. When the plate was annealed at 1373 K, rl phase was formed by a solid-state peritectoid reaction. A first-order magnetic phase transition occurred in the vicinity of 188 K, and the effective refrigeration capacities reached 203.5J/kg and 209.7J/kg in plates annealed for I h and 3 h, respectively, under a magnetic field change of 3T. It is suggested that centrifugal casting may become a new approach to prepare high-performance La-Fe-Si magnetocaloric plates for prac- tical applications, which could largely accelerate the formation of rl phase during high-temperature heat-treatment process due to refined and homogeneous honeycombed microstructure.
基金co-supported by the National Natural Science Foundation of China-China(No.11302011)the Specialized Research Fund for the Doctoral Program of Higher Education-China(No.20131102120051)
文摘A flight dynamics model based on elastic blades for helicopters is developed.Modal shape analysis is used to describe the rotating elastic blades for the purpose of reducing the elastic degrees of freedom for blades.The analytical result is employed to predict the rotor forces and moments.The equilibrium equation of the flight dynamics model is then constructed for the elastic motion for blades and the rigid motion for other parts.The nonlinear equation is further simplified,and the gradient descent algorithm is adopted to implement the trim simulation.The trim analysis shows that the effect of blade elasticity on the accuracy of rotor forces and moments is apparent at high speed,and the proposed method presents good accuracy for trim performance.The timedomain response is realized by a combination of the Newmark method and the adaptive RungeKutta method.The helicopter control responses of collective pitch show that the response accuracy of the model at a yaw-and-pitch attitude is improved.Finally,the influence of blade elasticity on the helicopter dynamic response in low-altitude wind shear is investigated.An increase in blade elasticity reduces the oscillation amplitude of the yaw angle and the vertical speed by more than 70%.Compared with a rigid blade,an elastic blade reduces the vibration frequency of the angular velocity and results in a fast return of the helicopter to its stable flight.
基金supported by the National Natural Science Foundation of China(No.11672018).
文摘The modeling of dynamic stall aerodynamics is essential to stall flutter, due to the flow separation in a large-amplitude pitching oscillation process. A newly neural network based Reduced Order Model(ROM) framework for predicting the aerodynamic forces of an airfoil undergoing large-amplitude pitching oscillation at various velocities is presented in this work. First, the dynamic stall aerodynamics is calculated by solving RANS equations and the transitional SST-γ model. Afterwards, the stall flutter bifurcation behavior is calculated by the above CFD solver coupled with structural dynamic equation. The critical flutter speed and limit-cycle oscillation amplitudes are consistent with those obtained by experiments. A newly multi-layer Gated Recurrent Unit(GRU) neural network based ROM is constructed to accelerate the calculation of aerodynamic forces. The training and validation process are carried out upon the unsteady aerodynamic data obtained by the proposed CFD method. The well-trained ROM is then coupled with the structure equation at a specific velocity, the Limit-Cycle Oscillation(LCO) of stall flutter under this flow condition is predicted precisely and more quickly. In order to predict both the critical flutter velocity and LCO amplitudes after bifurcation at different velocities, a new ROM with GRU neural network considering the variation of flow velocities is developed. The stall flutter results predicted by ROM agree well with the CFD ones at different velocities. Finally, a brief sensitivity analysis of two structural parameters of ROM is carried out. It infers the potential of the presented modeling method to depict the nonlinearity of dynamic stall and stall flutter phenomenon.
基金co-supported by the National Natural Science Foundation of China(No.11672018)the Fundamental Research Funds for the Central Universities,China(No.YWF-23-SDHK-L-002).
文摘This paper focuses on the effect of the phase offset of Leading-Edge(LE)morphing on the aerodynamic characteristics of a pitching NACA0012 airfoil.Assuming an unstretched camber and using polynomial interpolation,an explicit expression for LE nonlinear morphing is proposed and implemented for the large pitching motion of the airfoil.Flow field results and aerodynamic forces are obtained by solving the unsteady Reynolds-averaged Navier-Stokes equations for both the airfoil’s pitching motion and LE morphing.Furthermore,the index of instantaneous aerodynamic power is used to quantify the work done by the airflow in a dynamic process.According to the instantaneous aerodynamic power and energy map,which denotes the energy transfer between the airfoil’s oscillation and flow field,the airfoil is subject to stall flutter.The results show that LE morphing with an optimal phase offset of 315°reduces the energy extraction from the flow field,suppressing the stall flutter instability.This optimal phase offset is effective at different pitching axis positions of the airfoil.The results signify that LE morphing can suppress stall flutter by advancing the occurrence of the first LE vortex and increasing the nose-down moment during the upstroke period.
基金supported by the National Natural Science Foundation of China(Grant No.82200153 to Yuting Dai,Grant Nos.82350710226 and 82370178 to Kankan Wang,Grant No.32170663 to Hai Fang,Grant No.82200116 to Fan Zhang)the National Key R&D Program of China(Grant No.2023YFA1800401 to Kankan Wang)+1 种基金the Interdisciplinary Program of Shanghai Jiao Tong University(Grant No.YG2022QN008 to Yuting Dai)the Innovative Research Team of High-Level Local Universities in Shanghai,China.
文摘Precise mapping of leukemic cells onto the known hematopoietic hierarchy is important for understanding the cell-of-origin and mechanisms underlying disease initiation and development.However,this task remains challenging because of the high interpatient and intrapatient heterogeneity of leukemia cell clones as well as the differences that exist between leukemic and normal hematopoietic cells.Using single-cell RNA sequencing(scRNA-seq)data with a curated clustering approach,we constructed a comprehensive reference hierarchy of normal hematopoiesis.This reference hierarchy was accomplished through multistep clustering and annotating over 100,000 bone marrow mononuclear cells derived from 25 healthy donors.We further employed the cosine distance algorithm to develop a likelihood score to determine the similarities of leukemic cells to their putative normal counterparts.Using our scoring strategies,we mapped the cells of acute myeloid leukemia(AML)and B cell precursor acute lymphoblastic leukemia(BCP-ALL)samples to their corresponding counterparts.The reference hierarchy also facilitated bulk RNA sequencing(RNA-seq)analysis,enabling the development of a least absolute shrinkage and selection operator(LASSO)score model to reveal subtle differences in lineage aberrancy within AML or BCP-ALL patients.To facilitate interpretation and application,we established an R-based package(HematoMap)that offers a fast,convenient,and user-friendly tool for identifying and visualizing lineage aberrations in leukemia from scRNA-seq and bulk RNA-seq data.Our tool provides curated resources and data analytics for understanding leukemogenesis,with the potential to enhance leukemia risk stratification and personalized treatments.The HematoMap is available at https://github.com/NRCTM-bioinfo/HematoMap.
基金This work was supported by the National Natural Science Foundation of China(Nos.82070147,81570122,and 81770205)the National Key Research and Development Program(No.2016YFC0902800)+2 种基金the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.20161303)the Innovation Foundation for Doctoral Students of Shanghai Jiao Tong University School of Medicine(Research Grant BXJ201815)the Center for HPC at Shanghai Jiao Tong University.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘B-cell precursor acute lymphoblastic leukemia(BCP-ALL)is characterized by genetic alterations with high heterogeneity.Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology.Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes,such as DUX4 rearrangements,MEF2D rearrangements,ZNF384/ZNF362 rearrangements,NUTM1 rearrangements,BCL2/MYC and/or BCL6 rearrangements,ETV6-RUNX1-like gene expression,PAX5alt(diverse PAX5 alterations,including rearrangements,intragenic amplifications,or mutations),and hotspot mutations PAX5(p.Pro80Arg)with biallelic PAX5 alterations,IKZF1(p.Asn159Tyr),and ZEB2(p.His1038Arg).These molecular subtypes could be classified by gene expression patterns with RNA-seq technology.Refined molecular classification greatly improved the treatment strategy.Multiagent therapy regimens,including target inhibitors(e.g.,imatinib),immunomodulators,monoclonal antibodies,and chimeric antigen receptor T-cell(CAR-T)therapy,are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management.We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.
基金This work was supported in part by grants from the National Key Research and Development Program of China(no.2017YFA0505200)the National Basic Research Program of China(973 Program)(no.2015CB910403)+3 种基金the National Natural Science Foundation of China(81700475,81670139,81570118,and 81570112)Natural Science Foundation of Shanghai(16ZR1427800)the Science and Technology Committee of Shanghai(15401901800)the Innovation Program of Shanghai Municipal Education Commission(13YZ028).
文摘T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modifications,such as ubiquitination,regulate NOTCH1 stability,activity,and localization.However,the specific deubiquitinase that affects NOTCH1 protein stability remains unestablished.Here,we report that ubiquitin-specific protease 7(USP7)can stabilize NOTCH1.USP7 deubiquitinated NOTCH1 in vivo and in vitro,whereas knockdown of USP7 increased the ubiquitination of NOTCH1.USP7 interacted with NOTCH1 protein in T-ALL cells,and the MATH and UBL domains of USP7 were responsible for this interaction.Depletion of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo,accompanied by downregulation of the NOTCH1 protein level.Similarly,pharmacologic inhibition of USP7 led to apoptosis of T-ALL cells.More importantly,we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples,and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells,indicating the clinical relevance of these findings.Overall,our results demonstrate that USP7 is a novel deubiquitinase that stabilizes NOTCH1.Therefore,USP7 may be a promising therapeutic target in the currently incurable T-ALL.
基金This study was supported by the National Natural Science Foundation of China(No.81800147)Shanghai Sailing Program(No.18YF1413700)+2 种基金the National Key Research and Development Plan of China(No.2018YFA0107800)the National Natural Science Foundation of China(No.81890994)the National Key Research and Development Plan of China(No.2017YFA0506200)。
文摘OriginalTranslation t(8;21)(q22;q22)acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy with a high relapse rate in China.Two leukemic myeloblast populations(CD34^(+)CD117^(dim) and CD34^(+)CD117^(bri))were previously identified in t(8;21)AML,and CD34^(+)CD117^(dim) cell proportion was determined as an independent factor for this disease outcome.Here,we examined the impact of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression on t(8;21)AML clinical prognosis.In this study,85 patients with t(8;21)AML were enrolled.The mRNA expression levels of CD34^(+)CD117^(dim)-associated genes(LGALS1,EMP3,and CRIP1)and CD34^(+)CD117^(bri)-associated genes(TRH,PLAC8,and IGLL1)were measured using quantitative reverse transcription PCR.Associations between gene expression and clinical outcomes were determined using Cox regression models.Results showed that patients with high LGALS1,EMP3,or CRIP1 expression had significantly inferior overall survival(OS),whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis.Univariate analysis revealed that CD19,CD34^(+)CD117^(dim) proportion,KIT mutation,minimal residual disease(MRD),and expression levels of LGALS1,EMP3,CRIP1,TRH and PLAC8 were associated with OS.Multivariate analysis indicated that KIT mutation,MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS.Identifying the clinical relevance of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21)AML.
基金This work was supported by the Key Project of National Natural Science Foundation of China(No.81530006 to Ruibao Ren)Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01 to Ruibao Ren)+2 种基金National Natural ScienceFoundation of China(No.81870112 to Ruibao Ren,No.81770171 to Bo Jiao,and No.81970134 to Ping Liu)Samuel Waxman Cancer Research Foundation(to Ruibao Ren)the Innovative Research Team of High-level Local Universities in Shanghai.
文摘More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
基金supported by the National Research Center for Translational Medicine under grant number NRCTM(SH)2023-15(to Z-B.W.)Fundamental Research Funds for the Central Universities(No.YG2023ZD06 to Z-B.W.)+3 种基金National Natural Science Foundation of China(82472640 to Z-B.W.,82373131 and 82573142 to S-J.L.,82200153 to Y-T.D.,82500265 to S-S.Y.)Health care leader of Shanghai Municipal Health Commission(No.2022LJ006 to Z-B.W.)the Natural Science Foundation of Shanghai,China(25ZR1402349 to S-S.Y.)the Innovative Research Team of HighLevel Local Universities in Shanghai.
文摘Pituitary neuroendocrine tumors(PitNETs)are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis,yet their regulatory effects on peripheral immune networks remain poorly characterized.Here,we systematically analyzed bulk RNA sequencing(RNA‑seq)from 883 PitNET tumors,108 PitNET‑associated peripheral blood mononuclear cells(PBMC)samples,and 175 healthy PBMC controls,combined with 69 single‑cell RNA sequencing(scRNA-seq)samples covering tumors,normal pituitaries,as well as tumor‑derived and normal PBMCs.We identified a systemic immune disequilibrium in PitNET patients,characterized by increased circulating lymphocyte proportions,accompanied by upregulated cytokine-receptor interaction signatures.Notably,tumor resection reversed this imbalance,as supported by the normalization of monocyte and neutrophil counts,validated by flow cytometry and routine blood data from 600 samples(200 healthy controls and 200 PitNET patients with paired pre-and post-surgery follow‑up).Trajectory analysis identified terminally differentiated,secretory-specialized cell populations with lineage-specific hormone and cytokine hypersecretion.Ligand-receptor inference suggested these tumor-derived factors potentially engage circulating immune cell receptors.A random‑forest classifier based on PBMC transcriptomes distinguished PitNET subtypes,underscoring the diagnostic potential of peripheral immune signatures.Furthermore,in an estrogen-induced rat model,elevated PRL level coincided with the same peripheral immune skewing.Overall,our work provides a valuable resource and demonstrates PitNETs can be systemic immune modulators,where intrinsic hormone secretory activity and monocyte-lymphocyte imbalance collectively drive peripheral immune dysfunction.
基金supported by the State Key Laboratory of Medical Genomics,the Double First-Class Project(No.WF510162602)from the Ministry of EducationOverseas Expertise Introduction Project for Discipline Innovation(111 Project,No.B17029)+2 种基金National Natural Science Foundation of China(Nos.82230006,82470206,32170663,32470681,and 81770124)Innovative Research Team of High-level Local Universities in Shanghai and CAMS Innovation Fund for Medical Sciences(No.CIFMS 2021-I2M-5-010)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.RC20210190).
文摘Chimeric antigen receptor T-cell(CAR-T)therapy has been successfully applied in clinical treatment,especially for hematologic malignancies such as multiple myeloma(MM),but its broad application is limited by cytokine release syndrome(CRS),a potentially life-threatening complication.Although metabolic alterations are known to accompany CRS,predictive biomarkers for its onset,severity,and associated metabolic remodeling remain unknown,hindering proactive clinical management.Here,we analyzed longitudinal serum metabolic profiles from 19 patients with relapsed/refractory MM receiving CAR-T therapy,with validation in an independent cohort of 23 patients.We observed dysregulated arginine metabolism that progressed alongside clinical CRS.At pre-lymphodepletion(Day–5),over half of differentially abundant metabolites were enriched in unsaturated fatty acid(UFA)synthesis pathways,which were exclusively upregulated in patients who later developed severe CRS.Furthermore,two lysophosphatidylcholines,namely,lysoPC(16:0)and lysoPC(15:0),were significantly associated with delayed CRS onset,with elevated concentrations correlated with a prolonged time to onset;this association was independently validated.These findings revealed that arginine metabolism was a pathological axis in CRS,UFAs were severity predictors,and specific lysoPCs were modulators of onset time.Collectively,they provide proactive CRS management,addressing critical gaps in predictive biomarkers to advance the safe,broad CAR-T application in MM.
