Aerodynamic characteristics of a pitching airfoil with leading-edge morphing

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.

Stall flutter prediction based on multi-layer GRU neural network

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.

Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblasti

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.

Dynamic response analysis under atmospheric disturbances for helicopters based on elastic blades

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.

High-temperature phase transition behavior and magnetocaloric effect in a sub-rapidly solidified La–Fe–Si plate produced by centrifugal casting

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.

Clinical significance of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression in t(8;21)acute myeloid leukemia

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.

USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia

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.

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma

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.