Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.

We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.

A careful theoretical analysis of the excitation of Alfvén eigenmodes (AEs), such as TAE (toroidicity-induced AE) and RSAE (reversed shear AE), by superalfvenic energetic particles is required for reliable predictions of energetic ion relaxation in present day fusion experiments. This includes the evaluation of different AE damping mechanisms including radiative and continuum dampings which are the focus of this study. A recent comprehensive benchmark of different eigenmode solvers including gyrokinetic, gyrofluid and hybrid magenetohydrodynamics (MHD) has shown that employed models may have deficiencies when addressing some of them (Taimourzadeh et al., Nucl. Fusion, vol. 59, 2019, 066006). In this paper, we are studying the radiative and continuum dampings of RSAEs in details which were missing in hybrid NOVA/NOVA-C calculations to prepare a NOVA-C package with a substantial upgrade. Both dampings require the finite Larmor radius (FLR) corrections to AE mode structures to be accounted for. Accurately calculating different damping rates and understanding their parametric dependencies, we resolve the limitation coming out of the perturbative approach. In particular, here, the radiative damping is included perturbatively, whereas the continuum damping is computed non-perturbatively. Our comparison leads to the conclusion that the non-perturbative treatment of the unstable RSAE modes is needed to find the agreement with the gyrokinetic calculations. We expect that the RSAE mode structure modification plays a dominant role in determining the RSAE stability.

In this paper, a brand-new adaptive fault-tolerant non-affine integrated guidance and control method based on reinforcement learning is proposed for a class of skid-to-turn (STT) missile. Firstly, considering the non-affine characteristics of the missile, a new non-affine integrated guidance and control (NAIGC) design model is constructed. For the NAIGC system, an adaptive expansion integral system is introduced to address the issue of challenging control brought on by the non-affine form of the control signal. Subsequently, the hyperbolic tangent function and adaptive boundary estimation are utilised to lessen the jitter due to disturbances in the control system and the deviation caused by actuator failures while taking into account the uncertainty in the NAIGC system. Importantly, actor-critic is introduced into the control framework, where the actor network aims to deal with the multiple uncertainties of the subsystem and generate the control input based on the critic results. Eventually, not only is the stability of the NAIGC closed-loop system demonstrated using Lyapunov theory, but also the validity and superiority of the method are verified by numerical simulations.

A simplified configuration was developed to facilitate the mode transition process within an over-under Turbine-Based Combined Cycle (TBCC) inlet. Leveraging dynamic mesh technology, an unsteady numerical simulation of the mode transition was conducted, emphasising the flow characteristics of the mode transition and the impact of key similarity criteria numbers. The findings indicate that at an incoming Mach number of 2.0, the mode transition is paired with a continuous alteration in the capture mass flow of the high-speed duct. This continual change instigates the inlet unstarting, with subsequent flow characteristics being contingent on the historical effect, exhibiting a degree of hysteresis characteristics. When the scale effect is considered, it is observed that a larger model scale results in higher Reynolds (Re) and Strouhal (St) numbers. This directly contributes to a notable delay in the unstart moment, a decrease in the unstart interval, and an enlargement of the hysteresis loop. An examination of control variables reveals that the Re number marginally influences mode transition characteristics, while the St number’s effect constitutes approximately 90% of the scale effect. This conclusively demonstrates that the St number is the predominant similarity criterion number in the mode transition process.

To enhance the impact resistance capacity and ensure the floatability of aircraft after ditching, the slamming response of three types of aircraft sub-floor structures are investigated including the flat, cylindrical and ellipsoidal under floor. A coupled Finite Element-Smooth Particle Hydrodynamic (FE-SPH) method is employed with focus on non-linear structural collapse in fluid-structure interaction. The material is defined by bilinear elastic plastic law, and the strain rate effect is taken into account. Further, comparison and analyses are performed in terms of acceleration, local pressure and strains at different speeds. Results show that conventional flat sub floor structures perform poorly during ditching due to excessive peak acceleration and pressure. By contrast, the peak acceleration of ellipsoidal under floor is lower at all measured speeds and the pressure on the sides is reduced. Moreover, the ellipsoidal sub-floor with bi-directional curvature generates smaller plastic strain and deflection of skin, demonstrating better mechanical properties in water impact scenarios.

Aiming at alleviating the adverse influence of coupling unmodeled dynamics, actuator faults and external disturbances in the attitude tracking control system of tilt tri-rotor unmanned aerial vehicle (UAVs), a neural network (NN)-based robust adaptive super-twisting sliding mode fault-tolerant control scheme is designed in this paper. Firstly, in order to suppress the unmodeled dynamics coupled with the system states, a dynamic auxiliary signal, exponentially input-to-state practically stability and some special mathematical tools are used. Secondly, benefiting from adaptive control and super-twisting sliding mode control (STSMC), the influence of the unexpected chattering phenomenon of sliding mode control (SMC) and the unknown system parameters can be handled well. Moreover, NNs are employed to estimate and compensate some unknown nonlinear terms decomposed from the system model. Based on a decomposed quadratic Lyapunov function, both the bounded convergence of all signals of the closed-loop system and the stability of the system are proved. Numerical simulations are conducted to demonstrate the effectiveness of the proposed control method for the tilt tri-rotor UAVs.

In a recent survey of nematodes associated with tobacco in Shandong, China, the root-lesion nematode Pratylenchus coffeae was identified using a combination of morphology and molecular techniques. This nematode species is a serious parasite that damages a variety of plant species. The model plant benthi, Nicotiana benthamiana, is frequently used to study plant-disease interactions. However, it is not known whether this plant species is a host of P. coffeae. The objectives of this study were to evaluate the parasitism and pathogenicity of five populations of the root-lesion nematode P. coffeae on N. benthamiana. N. benthamiana seedlings with the same growth status were chosen and inoculated with 1,000 nematodes per pot. At 60 days after inoculation, the reproductive factors (Rf = final population densities (Pf)/initial population densities (Pi)) for P. coffeae in the rhizosphere of N. benthamiana were all more than 1, suggesting that N. benthamiana was a good host plant for P. coffeae. Nicotiana. benthamiana infected by P. coffeae showed weak growth, decreased tillering, high root reduction, and noticeable brown spots on the roots. Thus, we determined that the model plant N. benthamiana can be used to study plant-P. coffeae interactions.

We present the results of a combined experimental and theoretical investigation of sheet evolution, expansion and retraction, under unsteady fragmentation upon drop impact on a surface of comparable size to that of the drop. We quantify and model the effect of the continuous time-varying – unsteady – shedding of droplets from the sheet via its bounding rim. We present and validate especially developed advanced image processing algorithms that quantify, with high accuracy, the key quantities involved in such unsteady fragmentation, from sheet, to rim, to ligaments, to droplet properties. With these high precision measurements, we show the important effect of continuous unsteady droplet shedding on the sheet dynamics. We combine experiments and theory to derive and validate governing equations of the sheet that incorporate such continuous shedding – associated with continuous loss of momentum and mass – from unsteady fragmentation. Combining this theory with the universal unsteady rim dynamics discovered in Wang et al. (Phys. Rev. Lett., vol. 120, 2018, 204503), we show that the governing equation of the sheet can be reduced to a continuous-shedding, non-Galilean Taylor–Culick law, from which we deduce new analytical expressions for the time evolution of the sheet radius. We show the robustness of the predictions to changes of fluid properties, including surface tension and moderate fluid viscosity and elasticity, including use of physiological mucosalivary fluid. We also reconcile prior literature's inconsistent experimental results on the sheet dynamics upon drop impact.

Coupling of clearance joint and harsh aerodynamic heating environment is an inevitable nonlinear factor in folding mechanism of the fin of high-speed aircrafts that remarkably modifies natural frequencies and modes of vibration from the initial design state. However, accurately predicting dynamic properties of deployable fin with full consideration of these effects is not common industry practice. A practical semi-analytical model based on Hertz contact theory and ESDU-78035 model is proposed in this study to investigate high-temperature connection stiffness of local hinged–locked mechanisms. Material property degradation and clearance variation caused by thermal expansion are comprehensively considered and quantified in this model. Vibration characteristics of the assembled deployable fin are then solved using finite element method (FEM). The real-time evolutionary process of thermal mode of the fin is discussed. And natural frequencies of fixed-value and time-varying connection stiffness are compared. The simulation results of this study demonstrate that the relative error of structure temperature between the sequential approach and fully coupled simulations is less than 6.98%. The connection stiffness (slope of the load-displacement curve) of the folding mechanism under high temperature conditions decreases by 3.52%, and the variation is mainly caused by the degradation of the elastic modulus of the material, while the clearance change due to the thermal expansion has no significant effect on the slope. The natural frequency of the deployable fin exhibits an inverse correlation with the temperature change trend, and the first three frequencies decrease by 1.67, 7.75, and 16.28 Hz compared to the initial value, respectively.