Scott Morris

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology. The Cancer Genome Atlas (TCGA) project reports here its analysis of messenger RNA and microRNA expression, promoter methylation, DNA copy number and exome sequences in 489 high-grade serous ovarian adenocarcinomas. The analyses help establish new tumour subtypes. Among other insights is the finding that while the gene encoding p53 tumour suppressor is mutated in almost all tumours, nine other loci including NF1, BRCA1, BRCA2, RB1 and CDK12 carry recurrent albeit low-prevalence mutations. Homologous recombination is defective in about half of the tumours studied, and Notch and FOXM1 signalling are involved in the pathophysiology.

An aerodynamic instability known as stall occurs in axial compressors as the mass flow rate is reduced and the blade loading reaches its limit. At this limiting condition, an easily recognizable flow breakdown process, known as spike-type stall inception, is observed in most modern compressors. This article begins by examining measurements from both low- and high-speed compressors to explain the characteristic features of spike-type stall. This is followed by a review of past work on compressor stability and an assessment of recent advances in this field. Included here is a study of the three-dimensional flow features that typify spike formation and its eventual growth into a mature stall cell. We also consider the formation criteria for spike-type stall and the means for early detection and possible control. On the computational side, a possible mechanism for spike formation is identified from three-dimensional studies of the flow in the rotor tip region. This mechanism involves tip-clearance backflow at the blade's trailing edge in combination with forward spillage of tip-leakage flow at the leading edge. This flow pattern implies that a successful stall-control technology will have to rely on an effective means of suppressing tip-clearance backflow and forward spillage.

Tonal noise generated by airfoils at low to moderate Reynolds number is relevant for applications in, for example, small-scale wind turbines, fans and unmanned aerial vehicles. Coherent and convected vortical structures scattering at the trailing edge from the pressure or suction sides of the airfoil have been identified to be responsible for such tonal noise generation. Controversy remains on the respective significance of pressure- and suction-side events, along with their interaction for tonal noise generation. The present study surveys the regimes of tonal noise generation for low to moderate chord-based Reynolds number between $\mathit{Re}_{c}=0.3\times 10^{5}$ and $2.3\times 10^{5}$ and effective angle of attack between $0^{\circ }$ and $6.3^{\circ }$ for the NACA 0012 airfoil profile. Extensive acoustic measurements with smooth surface and with transition to turbulence forced by boundary layer tripping are presented. Results show that, at non-zero angle of attack, tonal noise generation is dominated by suction-side events at low Reynolds number and by pressure-side events at high Reynolds number. At smaller angle of attack, interaction between events on the two sides becomes increasingly important. Particle image velocimetry measurements complete the information on the flow field structure in the source region around the trailing edge. The influences of both angle of attack and Reynolds number on tonal noise generation are explained by changes in the mean flow topology, namely the presence and location of reverse flow regions on the two sides. Data gathered from experimental and numerical studies in the literature are reviewed and interpreted in view of the different regimes.

A flow-excited Helmholtz resonator was investigated experimentally and theoretically. The analysis was focused on a simplified momentum balance integrated over the region of the orifice. The resulting expressions were used to guide an experimental programme designed to obtain measurements of the resonator pressure under flow excitation, as well as the dynamics of the shear layer in the orifice using particle image velocimetry (PIV). The pressure measurements indicated a number of distinctive features as the flow speed varied. The PIV results provided a detailed representation of the shear layer vorticity field, as well as the equivalent hydrodynamic forcing of the resonator. The forcing magnitude was found to be roughly constant over a range of flow speeds. A model was proposed that provides a prediction of the resonator pressure fluctuations based on the thickness of the approach boundary layer, the free stream speed and the acoustic properties of the resonator. The model was shown to provide an accurate representation of the resonating frequency as well as the magnitude of the resonance to within a few decibels.

This communication presents the results and conclusions of an experimental study of the near-separation region of a single-stream shear layer. The momentum thickness at separation ( $x\,{=}\,0$ ) was $\theta_0\,{=}\,9.6$ mm, with Reynolds number $\hbox{\itshape Re}_\theta\,{=}\,4650$ . Boundary layer separation was caused by a sharp $90^{\circ}$ edge. Detailed single- and multi-point measurements of the velocity field were acquired at the streamwise locations $0\,{<}\,x/\theta_0\,{<}\,100$ . This represents the transition region between two of the canonical turbulent shear flows: the zero-pressure-gradient turbulent boundary layer and the single-stream shear layer. From the viewpoint of a separating boundary layer, the results describe how the turbulent flow reacts to a sudden change in wall boundary conditions. From the viewpoint of the developed shear layer, the results describe the transition to the self-similar region. The data acquired suggest that the initial shear layer instability occurs in the region very near separation ( $x\,{\approx}\,\theta_0$ ), and that it involves only the vorticity filaments which originate in the near-wall region of the upstream boundary layer. This ‘near-wall region’ roughly defines the origin of a narrow wedge-shaped domain that was identified from the velocity statistics. This domain is termed the ‘sub-shear layer’. The statistics of the velocity field in the region bounded by the sub-shear layer and the free-stream flow were found to represent the normative continuation of the upstream boundary layer. The sub-shear layer has been found to exhibit many of the standard features observed in fully developed shear layers. For example, velocity measurements on the entrainment side of the shear layer indicate that large-scale motions with spanwise coherence were observed. The streamwise dependence of the dominant frequency, convection velocity, and spanwise velocity correlation have been documented in order to characterize the sub-shear layer phenomenon.