Zonal large-eddy simulation of a fan tip-clearance flow, with evidence of vortex wandering

The flow in a fan test-rig is studied with combined experimental and numerical methods, with a focus on the tip-leakage flow. A zonal RANS/LES approach is introduced for the simulation: the region of interest at tip is computed with full large-eddy simulation (LES), while Reynolds-averaged Navier–Stokes (RANS) is used at inner radii. Detailed comparisons with the experiment show that the simulation gives a good description of the flow. In the region of interest at tip, a remarkable prediction of the velocity spectrum is achieved, over about six decades of energy. The simulation precisely captures both the tonal and broadband contents. Furthermore, a detailed analysis of the simulation allows identifying a tip-leakage vortex (TLV) wandering, whose influence onto the spectrum is also observed in the experiment. This phenomenon might be due to excitation by upstream turbulence from the casing boundary layer and/or the adjacent TLV. It may be a precursor of rotating instability. Finally, considering the outlet duct acoustic spectrum, the vortex wandering appears to be a major contribution to noise radiation

A Kalman filter adapted to the estimation of mean gradients in the large-eddy simulation of unsteady turbulent flows

A computationally-efficient method based on Kalman filtering is introduced to capture “on the fly” the low-frequency (or very large-scale) patterns of a turbulent flow in a large-eddy simulation (LES). This method may be viewed as an adaptive exponential smoothing in time with a varying cut-off frequency that adjusts itself automatically to the local rate of turbulence of the simulated flow. It formulates as a recursive algorithm, which requires only few arithmetic operations per time step and has very low memory usage. In practice, this smoothing algorithm is used in LES to evaluate the low-frequency component of the rate of strain, and implement a shear-improved variant of the Smagrosinky’s subgrid-scale viscosity. Such approach is primarily devoted to the simulation of turbulent flows that develop large-scale unsteadiness associated with strong shear variations. As a severe test case, the flow past a circular cylinder at Reynolds number (in the subcritical turbulent regime) is examined in details. Aerodynamic and aeroacoustic features including spectral analysis of the velocity and the far-field pressure are found in good agreement with various experimental data. The Kalman filter suitably captures the pulsating behavior of the flow and provides meaningful information about the large-scale dynamics. Finally, the robustness of the method is assessed by varying the parameters entering in the calibration of the Kalman filter

Towards Hybrid CAA with ground effects

CAA based on the Linearised Euler Equations (LEE) is applied to propagate aerodynamic sound over an extended distance including ground effects. The LEE are coupled to data from an LES via an acoustic analogy to follow-up the sound from the source to the extended far field: the complete chain is illustrated on the sound generated by a cylinder in a M ∼ 0.2 and Re ∼ 48000 flow. A very good agreement is found in free field between the approach based on the Ffowcs-Williams & Hawkings (FWH) analogy only and the combined FWH-LEE approach. The ability of the combined approach to handle complex boundary conditions is illustrated on the same data set with a rigid and a grassy ground

Zonal Large-Eddy Simulation of a Fan Tip-Clearance Flow, With Evidence of Vortex Wandering

The flow in a fan test-rig is studied with combined experimental and numerical methods, with a focus on the tip-leakage flow. A zonal RANS/LES approach is introduced for the simulation: the region of interest at tip is computed with full large-eddy simulation (LES), while Reynolds-averaged Navier-Stokes (RANS) is used at inner radii. Detailed comparisons with the experiment show that the simulation gives a good description of the flow. In the region of interest at tip, a remarkable prediction of the velocity spectrum is achieved, over about six decades of energy. The simulation precisely captures both the tonal and broadband contents. Furthermore, a detailed analysis of the simulation allows identifying a tip-leakage vortex wandering, whose influence onto the spectrum is also observed in the experiment. This phenomenon might be due to excitation by upstream turbulence from the casing boundary layer and/or the adjacent tipleakage vortex. It may be a precursor of rotating instability. Finally, considering the outlet duct acoustic spectrum, the vortex wandering appears to be a major contribution to noise radiation

A recurrent RNA-binding domain is appended to eukaryotic aminoacyl-tRNA synthetases

Aminoacyl-tRNA synthetases of higher eukaryotes possess polypeptide extensions in contrast to their prokaryotic counterparts. These extra domains of poorly understood function are believed to be involved in protein–protein or protein–RNA interactions. Here we showed by gel retardation and filter binding experiments that the repeated units that build the linker region of the bifunctional glutamyl-prolyl-tRNA synthetase had a general RNA-binding capacity. The solution structure of one of these repeated motifs was also solved by NMR spectroscopy. One repeat is built around an antiparallel coiled-coil. Strikingly, the conserved lysine and arginine residues form a basic patch on one side of the structure, presenting a suitable docking surface for nucleic acids. Therefore, this repeated motif may represent a novel type of general RNA-binding domain appended to eukaryotic aminoacyl-tRNA synthetases to serve as a cis-acting tRNA-binding cofactor

Head-up displays in action video games: the effects of physical and semantic characteristics on player performance and experience

International audienceThis study aimed to investigate how different characteristics of head-up displays (HUDs) can impact the performance and subjective experience of players in action video games. HUDs are a very common way to display contextual information. However, very few studies have empirically investigated the influence of HUD design on player performance and experience from a human information processing perspective. Four experiments were conducted in which players of different levels of expertise played commercial action video games. The physical characteristics of HUD, i.e. the physical appearance of the information on screen such as size and color (Experiments 1-2), and the semantic characteristics, i.e. the composition (nature and content) of the information (Experiments 3-4), were manipulated. Player performance and subjective experience were systematically assessed. The results showed that players’ performance and experience were impacted when the semantic characteristics of the HUD elements were manipulated and when their nature was relevant to the main task players have to perform within the game. The performance of more experienced players was particularly affected in this case. In contrast, the results did not show that altering physical or semantic characteristics that were less relevant to the game main task would affect players’ performance and subjective experience

Targeting the Wnt Pathway and Cancer Stem Cells with Anti-progastrin Humanized Antibodies as a Potential Treatment for K-RAS-Mutated Colorectal Cancer

International audiencePatients with metastatic colorectal cancer suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for the self-renewal of colon CSCs, which is also a direct β-catenin/TCF4 target gene. In this study, we aimed to develop a novel targeted therapy to neutralize secreted progastrin to inhibit Wnt signaling, CSCs, and reduce relapses.Experimental Design:Antibodies (monoclonal and humanized) directed against progastrin were produced and selected for target specificity and affinity. After validation of their effectiveness on survival of colorectal cancer cell lines harboring B-RAF or K-RAS mutations, their efficacy was assessedin vitroandin vivo, alone or concomitantly with chemotherapy, on CSC self-renewal capacity, tumor recurrence, and Wnt signaling.Results:We show that anti-progastrin antibodies decrease self-renewal of CSCs bothin vitroandin vivo, either alone or in combination with chemotherapy. Furthermore, migration and invasion of colorectal cancer cells are diminished; chemosensitivity is prolonged in SW620 and HT29 cells and posttreatment relapse is significantly delayed in T84 cells, xenografted nude mice. Finally, we show that the Wnt signaling activityin vitrois decreased, and, in transgenic mice developing Wnt-driven intestinal neoplasia, the tumor burden is alleviated, with an amplification of cell differentiation in the remaining tumors.Conclusions:Altogether, these data show that humanized anti-progastrin antibodies might represent a potential new treatment for K-RAS-mutated colorectal patients, for which there is a crucial unmet medical need.Clin Cancer Res; 23(17); 5267-80. \textcopyright2017 AACR

LBA-5 ANCHOR CRC: a single-arm, phase 2 study of encorafenib, binimetinib plus cetuximab in previously untreated BRAF V600E-mutant metastatic colorectal cancer

Background BRAFV600E mutations are identified in 8-15% of metastatic colorectal cancer (mCRC) patients and confer a poor prognosis. In patients with BRAFV600E-mutant mCRC, the combination of encorafenib (ENCO) + cetuximab (CETUX) ± binimetinib (BINI) in second- and third-line therapy has demonstrated improved outcomes compared to standard therapies (BEACON CRC study). The ANCHOR CRC study was designed to investigate the triplet combination (ENCO + BINI + CETUX) in the first line setting of this population. Methods ANCHOR CRC is an open-label, single arm, two-stage design, phase 2 study in patients with BRAFV600E-mutant mCRC who did not receive any prior systemic therapy for metastatic disease. Patients received ENCO 300 mg orally QD + BINI 45 mg orally BID and CETUX IV weekly (250mg/m2 after a first dose of 400mg/m2) for the first 28 weeks and then once every two weeks (500mg/m2). The primary endpoint was confirmed Objective Response Rate (cORR) based on local review; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. Analysis for Stage 1 was performed after the first 40 evaluable patients with a centrally confirmed BRAFV600E mutation had completed four post-baseline tumor assessments or discontinued. At least 12 responses in Stage 1 were needed to initiate Stage 2 and to enroll 50 additional patients to complete the recruitment with a total of 90 patients in the study. Stage 1 analysis results are presented here. Results Forty-one BRAFV600E-mutant mCRC patients with a median age of 67 years old (61% of the patients were ≥ 65 years old) were enrolled in Stage 1 and received the triplet combination as first line metastatic treatment. At study entry, 56% of patients presented with ECOG PS 1, 78% had metastases to at least 2 organs and 51% had peritoneal metastasis. Forty patients were evaluable for efficacy (BRAFV600E mutation was not centrally confirmed for one patient). The investigator assessed cORR was 50% (95% confidence interval [CI], 33.8-66.2) with 85% of patients having a decrease in tumor size. The investigator measured median PFS was 4.9 months (95% CI, 4.4-8.1). Adverse events were consistent with those observed in prior studies with this triplet combination. Grade 3 or higher adverse events were seen in 68% of patients, the most common being: diarrhea (15%), acute kidney injury (12%) and anemia (12%). Conclusion The ANCHOR CRC study is the first prospective study using a BRAF inhibitor-based therapy in first line BRAFV600E-mutant mCRC. Despite the high risk features of the population enrolled in Stage 1, including high proportion of patients ≥ 65 years old and advanced stage at diagnosis (multiple metastatic sites with frequent peritoneal carcinomatosis), most patients had tumor regression. The safety profile was acceptable and toxicities remained manageable. The Stage 1 analysis exceeded the minimal number of confirmed responses and proceeded to enroll 54 additional patients in Stage 2 to complete the study recruitment