Grid generation for wall-modelled les of ship hydrodynamics in model scale

An unstructured grid generation approach for wall-modelled LES is proposed. The applicability of the approach is demonstrated for the simulation of the flow around an axisym- metric body, at Re-number 5.48 · 106, which is representable of model scale ship hydrodynamics. A numerical trip wire must be employed to induce resolved fluctuations in the simulated bound- ary layer. The predictive accuracy of the simulation technique is evaluated for the flow around the axisymmetric body, and for the computation of a turbulent boundary layer on a flat plate. For the flat plate, comparison is made with results from direct numerical simulation. For the axisymmetric body, results from wall-modelled LES, RANS and experimental measurements are compared

Predictive accuracy of wall-modelled large-eddy simulation on unstructured grids

The predictive accuracy of wall-modelled LES is influenced by a combination of the subgrid model, the wall model, the numerical dissipation induced primarily by the convective numerical scheme, and also by the density and topology of the computational grid. The latter factor is of particular importance for industrial flow problems, where unstructured grids are typically employed due to the necessity to handle complex geometries. Here, a systematic simulation-based study is presented, investigating the effect of grid-cell type on the predictive accuracy of wall-modelled LES in the framework of a general-purpose finite-volume solver. Following standard practice for meshing near-wall regions, it is proposed to use prismatic cells. Three candidate shapes for the base of the prisms are considered: a triangle, a quadrilateral, and an arbitrary polygon. The cell-centre distance is proposed as a metric to determine the spatial resolution of grids with different cell types. The simulation campaign covers two test cases with attached boundary layers: fully-developed turbulent channel flow, and a zero-pressure-gradient flat-plate turbulent boundary layer. A grid construction strategy is employed, which adapts the grid metric to the outer length scale of the boundary layer. The results are compared with DNS data concerning mean wall shear stress and profiles of flow statistics. The principle outcome is that unstructured simulations may provide the same accuracy as simulations on structured orthogonal hexahedral grids. The choice of base shape of the near-wall cells has a significant impact on the computational cost, but in terms of accuracy appears to be a factor of secondary importance

Application of Permutation Genetic Algorithm for Sequential Model Building–Model Validation Design of Experiments

YesThe work presented in this paper is motivated by a complex multivariate engineering problem associated with engine mapping experiments, which require efficient Design of Experiment (DoE) strategies to minimise expensive testing. The paper describes the development and evaluation of a Permutation Genetic Algorithm (PermGA) to support an exploration-based sequential DoE strategy for complex real-life engineering problems. A known PermGA was implemented to generate uniform OLH DoEs, and substantially extended to support generation of Model Building–Model Validation (MB-MV) sequences, by generating optimal infill sets of test points as OLH DoEs, that preserve good space filling and projection properties for the merged MB + MV test plan. The algorithm was further extended to address issues with non-orthogonal design spaces, which is a common problem in engineering applications. The effectiveness of the PermGA algorithm for the MB-MV OLH DoE sequence was evaluated through a theoretical benchmark problem based on the Six-Hump-Camel-Back (SHCB) function, as well as the Gasoline Direct Injection (GDI) engine steady state engine mapping problem that motivated this research. The case studies show that the algorithm is effective at delivering quasi-orthogonal space-filling DoEs with good properties even after several MB-MV iterations, while the improvement in model adequacy and accuracy can be monitored by the engineering analyst. The practical importance of this work, demonstrated through the engine case study, also is that significant reduction in the effort and cost of testing can be achieved.The research work presented in this paper was funded by the UK Technology Strategy Board (TSB) through the Carbon Reduction through Engine Optimization (CREO) project

Synchronization in G0/G1 enhances the mitogenic response of cells overexpressing the human insulin receptor A isoform to insulin

Evaluating mitogenic signaling specifically through the human insulin receptor (IR) is relevant for the preclinical safety assessment of developmental insulin analogs. It is known that overexpression of IR sensitizes cells to the mitogenic effects of insulin, but it is essentially unknown how mitogenic responses can be optimized to allow practical use of such recombinant cell lines for preclinical safety testing. We constitutively overexpressed the short isoform of the human insulin receptor (hIR-A, exon 11-negative) in L6 rat skeletal myoblasts. Because the mitogenic effect of growth factors such as insulin is expected to act in G0/G1, promoting S-phase entry, we developed a combined topoinhibition + serum deprivation strategy to explore the effect of G0/G1 synchronization as an independent parameter in the context of serum deprivation, the latter being routinely used to reduce background in mitogenicity assays. G0/G1 synchronization significantly improved the mitogenic responses of L6-hIR cells to insulin, measured by 3H-thymidine incorporation. Comparison with the parental L6 cells using phospho-mitogen-activated protein kinase, phospho-AKT, as well as 3H-thymidine incorporation end points supported that the majority of the mitogenic effect of insulin in L6-hIR cells was mediated by the overexpressed hIR-A. Using the optimized L6-hIR assay, we found that the X-10 insulin analog was more mitogenic than native human insulin, supporting that X-10 exhibits increased mitogenic signaling through the hIR-A. In summary, this study provides the first demonstration that serum deprivation may not be sufficient, and G0/G1 synchronization may be required to obtain optimal responsiveness of hIR-overexpressing cell lines for preclinical safety testing

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation). Whether or not these differences have clinical bearings (and among which patient populations) remains to be determined