Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells.This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy.
We present a procedure for coupling the finite element method (FEM) and the discrete element method (DEM) for analysis of the motion of particles in non-Newtonian fluids. Particles are assumed to be spherical and immersed in the fluid mesh. A new method for computing the drag force on the particles in a non-Newtonian fluid is presented. A drag force correction for non-spherical particles is proposed. The FEM-DEM coupling procedure is explained for Eulerian and Lagrangian flows and the basic expressions of the discretized solution algorithm are given. The usefulness of the FEM-DEM technique is demonstrated in its application to the transport of drill cuttings in wellbores.
Openhole, multi-stage fracturing systems are commonly used today in many applications, including unconventional shale gas reservoirs. As many as forty stages have been successfully completed in a single horizontal well and the industry is aiming even higher. One problem that has a major impact on job success is the ability to accurately calculate maximum pump rates for a given surface pump pressure. When frac fluid is pumped through a downhole multi-stage fracturing system, each time a new stage is completed, the flow splits at different sleeves in the completion string. To determine minimum surface pump pressure and maximum pump flow rate, predicting split flow rate and the resulting pressure loss at each stage is essential. Traditionally, laboratory tests and field experience are used to predict these values. However, these types of predictions are not possible for hydraulic fracturing jobs that use a multiple sliding sleeve system, as is commonly employed. To simulate the hydraulic fracturing process, the Computational Fluid Dynamics (CFD) approach has been used, as it is a proven methodology. However, extensive CFD analysis requires computational overhead and significant software and hardware costs. This paper presents a methodology which combines CFD and theoretical approaches to calculate split flow rate and pressure loss for non-Newtonian frac fluids in a multiple sliding sleeve system. These methods are incorporated into the multiple sliding sleeve design process and hydraulic fracturing plan optimization. The method can also be extended as a general solution for calculating pressure loss due to split flow.
Well Intervention Plug and Abandon (P&A) operations play an important role at the end of life cycle of a subsea well in safely dismantling the well such that the well no longer poses any environmental hazards. P&A operations for subsea wells require sophisticated and efficient downhole tools that can operate at downhole pressures safely and reduce Non-Productive Time (NPT). A Dual String Section Milling (DSSM) downhole tool removes two adjacent casings in single trip reducing NPT while conducting safe P&A operations is discussed in this paper. This paper’s objectives are two fold first is to utilize advanced computational fluid dynamics (CFD) to improve DSSM tool life span for safe and economical P&A operations and second is to develop methodology for a quick and reliable solution for field personnel by combining CFD results with known closed form hydraulic models. The DSSM tool must maintain a certain pressure drop and flow range to achieve optimum performance. Higher flow rates and pressures can reduce tool life and cause erosion/washouts due to higher flow velocities. To address these issues simultaneously numerical simulations are conducted to optimize the DSSM tool design and operating parameters. To prove validity of numerical results CFD simulation outputs are compared against available test data and a good match is observed. Three dimensional CFD simulations are conducted using pressure based algorithm for numerically solving Reynolds-Averaged Navier-stokes (RANS) equation using second order upwind discretization scheme and k-ε turbulence model. Extensive CFD results are utilized in generating flow coefficients for closed form hydraulics models to formulate pressure drop versus flow rate charts for field usage. CFD simulations are conducted for flow rates between 100 gpm to 700 gpm to understand flow characteristics and pressure drop distribution within DSSM tool. CFD simulations showcased the locations prone to washouts; particularly washouts were observed around 90 degrees bend angles. The washout locations indicated by CFD analysis matched very well against the available test data. The DSSM tool design was then optimized using CFD simulations such that fluid velocities were below washout velocity and also higher annular velocities were maintained to alleviate hole cleaning problem during milling operations. The pressure drop versus flow rates curves obtained using flow coefficients showed correct trends with higher pressure drop for higher flow rates and higher pressure drop for reduced nozzle size. Thus utilizing CFD analysis, optimization and laboratory testing, service life of DSSM tool was increased, thus saving substantially on field NPT.
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