Effects of channel cross-sectional geometry on long wave generation and propagation

Joint theoretical and experimental studies are carried out to investigate the effects of channel cross-sectional geometry on long wave generation and propagation in uniform shallow water channels. The existing channel Boussinesq and channel KdV equations are extended in the present study to include the effects of channel sidewall slope at the waterline in the first-order section-mean equations. Our theoretical results show that both the channel cross-sectional geometry below the unperturbed water surface (characterized by a shape factor kappa) and the channel sidewall slope at the waterline (represented by a slope factor gamma) affect the wavelength (lambda) and time period (Ts) of waves generated under resonant external forcing. A quantitative relationship between lambda, Ts, kappa, and gamma is given by our theory which predicts that, under the condition of equal mean water depth and equal mean wave amplitude, lambda and Ts increase with increasing kappa and gamma. To verify the theoretical results, experiments are conducted in two channels of different geometries, namely a rectangular channel with kappa[equivalent]1, gamma=0 and a trapezoidal channel with kappa=1.27, gamma=0.16, to measure the wavelength of free traveling solitary waves and the time period of wave generation by a towed vertical hydrofoil moving with critical speed. The experimental results are found to be in broad agreement with the theoretical predictions

Evolution of long water waves in variable channels

This paper applies two theoretical wave models, namely the generalized channel Boussinesq (gcB) and the channel Korteweg–de Vries (cKdV) models (Teng & Wu 1992) to investigate the evolution, transmission and reflection of long water waves propagating in a convergent–divergent channel of arbitrary cross-section. A new simplified version of the gcB model is introduced based on neglecting the higher-order derivatives of channel variations. This simplification preserves the mass conservation property of the original gcB model, yet greatly facilitates applications and clarifies the effect of channel cross-section. A critical comparative study between the gcB and cKdV models is then pursued for predicting the evolution of long waves in variable channels. Regarding the integral properties, the gcB model is shown to conserve mass exactly whereas the cKdV model, being limited to unidirectional waves only, violates the mass conservation law by a significant margin and bears no waves which are reflected due to changes in channel cross-sectional area. Although theoretically both models imply adiabatic invariance for the wave energy, the gcB model exhibits numerically a greater accuracy than the cKdV model in conserving wave energy. In general, the gcB model is found to have excellent conservation properties and can be applied to predict both transmitted and reflected waves simultaneously. It also broadly agrees well with the experiments. A result of basic interest is that in spite of the weakness in conserving total mass and energy, the cKdV model is found to predict the transmitted waves in good agreement with the gcB model and with the experimental data availabl

Propagation of solitary waves through signicantly curved shallow water channels

Propagation of solitary waves in curved shallow water channels of constant depth and width is investigated by carrying out numerical simulations based on the generalized weakly nonlinear and weakly dispersive Boussinesq model. The objective is to investigate the effects of channel width and bending sharpness on the transmission and reflection of long waves propagating through significantly curved channels. Our numerical results show that, when travelling through narrow channel bends including both smooth and sharp-cornered 90°-bends, a solitary wave is transmitted almost completely with little reflection and scattering. For wide channel bends, we find that, if the bend is rounded and smooth, a solitary wave is still fully transmitted with little backward reflection, but the transmitted wave will no longer preserve the shape of the original solitary wave but will disintegrate into several smaller waves. For solitary waves travelling through wide sharp-cornered 90°-bends, wave reflection is seen to be very significant, and the wider the channel bend, the stronger the reflected wave amplitude. Our numerical results for waves in sharp-cornered 90°-bends revealed a similarity relationship which indicates that the ratios of the transmitted and reflected wave amplitude, excess mass and energy to the original wave amplitude, mass and energy all depend on one single dimensionless parameter, namely the ratio of the channel width b to the effective wavelength [lambda][sub]e. Quantitative results for predicting wave transmission and reflection based on b/[lambda][sub]e are presented

Role of Protein Kinase C in Podocytes and Development of Glomerular Damage in Diabetic Nephropathy

The early glomerular changes in diabetes include a podocyte phenotype with loss of slit diaphragm proteins, changes in the actin cytoskeleton and foot process architecture. This review focusses on the role of the Protein Kinase C family in podocytes and points out the differential roles of classical, novel and atypical PKCs in podocytes. Some PKC-isoforms are indispensable for proper glomerular development and slit diaphragm maintenance whereas others might be harmful when activated in the diabetic milieu. Therefore some might be interesting treatment targets in the early phase of diabetes

Characterization Of The Molecular Mechanisms Involved In Ethionamide Activation in Mycobacteria

Ph.DDOCTOR OF PHILOSOPH

Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange

Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying mechanisms, hepatic amino acid uptake and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and (13)CO(2) were measured in six sheep fetuses before and in the last 2 h of a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes (P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively. R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001) from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained virtually zero throughout the experiment. We conclude that Dex decreases fetal hepatic glutamate output by increasing the routing of glutamate carbon into the citric acid cycle and by decreasing the hepatic uptake of glucogenic amino acids

Expression of mammalian GPCRs in C. elegans generates novel behavioural responses to human ligands

BACKGROUND: G-protein-coupled receptors (GPCRs) play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involve in vitro systems. Caenorhabditis elegans is a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studying in vivo GPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2) and chemokine receptor 5 (CCR5) in the gustatory neurons of C. elegans. RESULTS: Expression of Sstr2 and CCR5 in gustatory neurons allow C. elegans to specifically detect and respond to somatostatin and MIP-1α respectively in a robust avoidance assay. We demonstrate that mammalian heterologous GPCRs can signal via different endogenous G(α )subunits in C. elegans, depending on which cells it is expressed in. Furthermore, pre-exposure of GPCR transgenic animals to its ligand leads to receptor desensitisation and behavioural adaptation to subsequent ligand exposure, providing further evidence of integration of the mammalian GPCRs into the C. elegans sensory signalling machinery. In structure-function studies using a panel of somatostatin-14 analogues, we identified key residues involved in the interaction of somatostatin-14 with Sstr2. CONCLUSION: Our results illustrate a remarkable evolutionary plasticity in interactions between mammalian GPCRs and C. elegans signalling machinery, spanning 800 million years of evolution. This in vivo system, which imparts novel avoidance behaviour on C. elegans, thus provides a simple means of studying and screening interaction of GPCRs with extracellular agonists, antagonists and intracellular binding partners

COMPARISON OF EFFICACY AND SAFETY OF NEWER DRUGS APPROVED FOR THE TREATMENT OF MIGRAINE DISORDER: A REVIEW

Migraine is a recurrent throbbing or pulsing headache with moderate to severe pain intensity. The pain is often one side of the head with nausea and weakness symptoms. Around 12 percent of Americans, 9 percent of Asians experiences migraine and the prevalence is highest among South Koreans (22.3%). The outcome of chronic migraine treatment can be quite disheartening, causing patients to feel out of options who have tried multiple treatments with no results. Poor efficacy, tolerability and safety of migraine preventive therapy in clinical practice lead to poor compliance and failure of therapy. The mean change in number or frequency of headache is considered as the outcome measure of migraine prevention therapy. Upon comparing all migraine prevention therapy, the Fremanezumab, Eptinezumab, Galcanezumab and Erenumab were considered as the front runner in controlling the severity and frequency of migraine. Among these drugs, Erenumab was most effective in controlling the frequency of migraine episodes as it produces more than 50 percent reduction in the mean number of monthly migraine days (MMD) over week 9-week 12. In addition to drug therapy, adequate rest, balanced diet, yoga and meditation will help patients to get rid of migraine severity. A multi-dimensional approach is essential for better control over migraine symptoms