Lagrangian modelling of nonlinear viscous waves generated by moving seabed deformation

A Lagrangian flow model is used to investigate highly nonlinear, dispersive waves generated by moving seabed deformation (MSD) of an otherwise horizontal seabed. Applications include free surface wave responses to horizontal co-seismic displacements and to novel bed-driven wave making systems used in surfing competitions. This paper considers gravity waves in viscous liquid, without restrictions on wave steepness, dispersion coefficient, and flow regime. Numerical computations are carried out using a Moving Particle Explicit method, which provides a Lagrangian flow description with far fewer particles than existing meshless methods. We show that the MSD speed has different effects in shallow and intermediate water depths. In shallow water, raising the MSD speed to a transcritical value promotes generation of leading solitary waves as expected. In supercritical flow, the highly nonlinear dynamics promotes breaking of the precursor soliton. In intermediate depth, wave dynamics is dominated by nonlinearity and dispersion, which act concurrently to generate a large leading wave that travels faster than predicted by linear theory, followed by a train of dispersive, short, steep waves. These waves break, even at subcritical values of MSD speed. We show that strongly nonlinear viscous dynamics occurs in the presence of a steep seabed deformation. This triggers flow separation, linked to strong amplification of wave steepness. Finally, we show that an oscillating MSD is capable of generating higher harmonics by means of nonlinear wave–wave interactions. The model is validated and verified by comparison to previously published experimental data and approximate analytical solutions

Weakly nonlinear theory for dispersive waves generated by moving seabed deformation

We present a weakly nonlinear theory for the evolution of dispersive transient waves generated by moving seabed deformation. Using a perturbation expansion up to second order, we show that higher-order components affect mostly the leading wave and the region close to the deforming seabed. In particular, the leading wave in the nonlinear regime has higher crests and deeper troughs than the known linear solution, while the trough that propagates together with the moving seabed exhibits pulsating behaviour and has larger depth. We also validate the analytical model with experimental data and obtain good agreement between both approaches. Our results suggest a need to extend existing models that neglect the effects of wave dispersion and higher-order components, especially in view of practical applications in engineering and oceanography.</jats:p

Multi-directional focused wave group interactions with a plane beach

Numerical simulations and laboratory measurements are presented of multi-directional focused wave groups interacting with a plane beach. The numerical model is a two-dimensional-horizontal (2DH) hybrid flow solver, governed by a Boussinesq equation set with enhanced dispersion characteristics pre-breaking, and the nonlinear shallow water equations post-breaking. Waves are introduced into the model via an in-built multi-element piston wavemaker, allowing for complete reproduction of laboratory experiments. A wetting and drying algorithm models shoreline movement in both cross-shore and longshore directions. Predicted free surface motions of the multi-directional focused wave groups are in good agreement with wave gauge data from laboratory experiments previously carried out at the UK Coastal Research Facility (UKCRF) using a linear paddle wave generator. Both phase decomposition into Stokes-like harmonic components and wavelets provide insight into nonlinear interactions as the wave groups propagate up the beach. Free second-order error waves in a multi-directional wave group are smaller than for the corresponding uni-directional case, and spread laterally around the incoming wave group. Of the free error waves generated by linear paddle signals, only the low-frequency second-order error wave affects extreme run-up on the beach. By applying a second-order correction to the paddle signals used to generate a multi-directional wave group, it is shown that, whereas the long error wave causes a significant increase in the maximum run-up, the impact is not as severe as for the uni-directional analogue. Shoaling and run-up of the bound long waves in a spread sea are studied. Examination of the transverse structure of these subharmonic components reveals that sideways spreading in the inner surf zone contributes to reduced run-up in directionally spread groups

Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer (OvCa) most often derives from ovarian surface epithelial (OSE) cells. Several lines of evidence strongly suggest that increased exposure to progesterone (P4) protects women against developing OvCa. However, the underlying mechanisms of this protection are incompletely understood.</p> <p>Methods</p> <p>To determine downstream gene targets of P4, we established short term <it>in vitro </it>cultures of non-neoplastic OSE cells from six subjects, exposed the cells to P4 (10^-6M) for five days and performed transcriptional profiling with oligonucleotide microarrays containing over 22,000 transcripts.</p> <p>Results</p> <p>We identified concordant but modest gene expression changes in cholesterol/lipid homeostasis genes in three of six samples (responders), whereas the other three samples (non-responders) showed no expressional response to P4. The most up-regulated gene was <it>TMEM97 </it>which encodes a transmembrane protein of unknown function (MAC30). Analyses of outlier transcripts, whose expression levels changed most significantly upon P4 exposure, uncovered coordinate up-regulation of 14 cholesterol biosynthesis enzymes, insulin-induced gene 1, low density lipoprotein receptor, <it>ABCG1</it>, endothelial lipase, stearoyl- CoA and fatty acid desaturases, long-chain fatty-acyl elongase, and down-regulation of steroidogenic acute regulatory protein and <it>ABCC6</it>. Highly correlated tissue-specific expression patterns of <it>TMEM97 </it>and the cholesterol biosynthesis genes were confirmed by analysis of the GNF Atlas 2 universal gene expression database. Real-time quantitative RT-PCR analyses revealed 2.4-fold suppression of the <it>TMEM97 </it>gene expression in short-term cultures of OvCa relative to the normal OSE cells.</p> <p>Conclusion</p> <p>These findings suggest that a co-regulated transcript network of cholesterol/lipid homeostasis genes and <it>TMEM97 </it>are downstream targets of P4 in normal OSE cells and that <it>TMEM97 </it>plays a role in cholesterol and lipid metabolism. The P4-induced alterations in cholesterol and lipid metabolism in OSE cells might play a role in conferring protection against OvCa.</p

Robustness in Glyoxylate Bypass Regulation

The glyoxylate bypass allows Escherichia coli to grow on carbon sources with only two carbons by bypassing the loss of carbons as CO2 in the tricarboxylic acid cycle. The flux toward this bypass is regulated by the phosphorylation of the enzyme isocitrate dehydrogenase (IDH) by a bifunctional kinase–phosphatase called IDHKP. In this system, IDH activity has been found to be remarkably robust with respect to wide variations in the total IDH protein concentration. Here, we examine possible mechanisms to explain this robustness. Explanations in which IDHKP works simultaneously as a first-order kinase and as a zero-order phosphatase with a single IDH binding site are found to be inconsistent with robustness. Instead, we suggest a robust mechanism where both substrates bind the bifunctional enzyme to form a ternary complex

High Density Lipoprotein (HDL) Promotes Glucose Uptake in Adipocytes and Glycogen Synthesis in Muscle Cells

Background: High density lipoprotein (HDL) was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. Methods and Results: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1- [ 3 H]-2deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI) in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3) phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK) a were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-a were diminished in SR-BI knock-down 3T3-L1 cells. Conclusions: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells throug

Prevalence of challenging behaviour in adults with intellectual disabilities, correlates, and association with mental health

Purpose of Review To summarise findings about the prevalence and correlates of challenging behaviour in adults with intellectual disabilities from robust research. We also describe findings on the interplay between challenging behaviour and mental health. Recent Findings Recent studies that have utilised psychometrically evaluated tools, with clear operational definitions, show similar findings on the prevalence of challenging behaviour of about 1 in every 5–6 adults known to services. We describe common correlates identified such as communication impairments, severity of intellectual disability, and living in institutional settings or congregate care. We also describe the complex and multifaceted relationship between challenging behaviour and mental health. Summary Based on recent studies, we propose a revised framework model to help understand challenging behaviour. We propose a number of areas where more research is required, particularly the development of risk tools clinicians can utilise in practice