62 research outputs found

    Comprehensive molecular characterization of the hippo signaling pathway in cancer

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    Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

    An experimental study of rip channel flow

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    A laboratory study of the flow over a bar with a single rip channel has been performed. First, the well-known pattern of a bar circulation cell with a strong offshore-directed current out through the rip channel and a weaker onshore-directed return flow over the bar is documented. Then measurements of the three-dimensional structure of the flow in the area where the rip channel, the bar and the trough meet and well inside the rip channel are presented. These measurements reveal that 3D effects play an important role, and that a depth-integrated viewpoint may not always be sufficient for predicting the flow in the near bed region. Particle-tracking experiments illustrate the near bed flow pattern over the entire area. These demonstrate how the overall trajectory pattern changes as a function of the distance of wave breaking from the bar crest: For some conditions, the rip current is fed from the trough and for other conditions it is fed directly from the bar. Both the 3D measurements and the trajectory tests show the existence of a weaker onshore-directed near-bed drift in the area where the rip current ceases. Finally, in a series of sensitivity tests, measurements of the rip current intensity for different wave climate and water level conditions reveal a strong correlation between the rip current intensity and the wave height (both normalized)

    Generic design of V-Shape and Vane-Type Breakwaters to reduce green water load effects on deck structures and containers of ships: Case study

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    Using computational fluid dynamics as the key tool for analysis, this paper looks into the generic designs of two popular types of breakwater, i.e., V-shape breakwater and vane-type breakwater. These are common practices to prevent the intrusion of green water deep into the deck and to protect deck structures and containers from direct impact loading. A hydrodynamic model to present green water flow on deck is also summarized together with brief validation for its appropriateness. The geometrical parameters of these two breakwaters are systematically varied and the effects on their performance against green water are evaluated. The effectiveness of coping with green water loading of each type of breakwater is also analyzed and compared

    Numerical Modelling of Scour Around an Offshore Jacket Structure Using REEF3D

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    In the present paper, a numerical investigation of the scouring around offshore jacket structure is carried out. The open-source CFD model REEF3D is used for the numerical modelling. The model solves the Reynolds-averaged Navier–Stokes equations with k-ω turbulence closure to calculate the flow hydrodynamics. The simulated flow field is coupled with sediment transport module in the model to calculate the scouring process. The scouring calculations are based on the Exner formula. The free surface and sediment bed topography are captured with the level set method. Results discuss the numerical modelling of an in situ local scour around the jacket foundations at the C-power wind farm Thornton bank. The key finding from the paper is the local scour around the individual jacket foundations and the global scour which takes place in form of a saucer-shaped. Additionally, the hydrodynamics and the temporal evolution of the scouring process under the wave and current action are discussed. The implication of the study is to set up a CFD model for the hydrodynamics and the scour calculations around offshore jacket foundations
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