Interest in the numerical solution of acoustic inverse scattering problems arises in a number of areas. Examples include medical diagnostics, non-destructive industrial testing, geophysical prospecting for petroleum and minerals, and detection of earthquakes. The highly nonlinear and oscillatory nature of the probltm is one of the major difficulties one encounters in the construction of effective inversion algorithms. Schemes based on global or local linearization methods, or nonlinear optimization techniques, tend to work only when the index of refraction is almost constant. They develop serious convergence problems whenever the perturbation of the index of refraction increases. Limited successes in the solution of the inverse problems have been achieved only in one dimensional cases (Gelfand-Levitan and layer striping methods are among the most notable). These methods are generally unstable numerically since the procedures used to calculate the index of refraction are ill-conditioned. We present a method for the solution of inverse problems for the one dimensional Helmholtz equation. The scheme is based on a combination of the standard Riccati equation for the impedance function with a new trace formula for the derivative of the index of refraction, and can be viewed as a frequency domain version of the layer-stripping approach. The principal advantage of the procedure is that if the scatterer to be reconstructed has m > 1 continuous derivatives, the accuracy of the reconstruction is proportional to 1/am, where a is the highest frequency for which scattering data axe available. Thus, a smooth scatterer is reconstructed very accurately from a limited amount of available data. The scheme has an asymptotic cost 0(n 2 ), where n is the number of features to be recovered (as do classical layer-stripping algorithms), and is stable with respect to perturbations of the scattering data. The performance of the algorithm is illustrated by several numerical examples. Generalizations of this approach in two dimensions are discussed.

Background: Creatinine (Cr) has been implicated as an independent predictor of hypertension and exercise has been reported as adjunct therapy for hypertension. The purpose of the present study was to investigate the effect of continuous training programme on blood pressure and serum creatinine concentration in black African subjects with hypertension. Methods: Three hundred and fifty seven male patients with mild to moderate (systolic blood pressure [SBP] between 140-180 & diastolic blood pressure [DBP] between 90-109 mmHg) essential hypertension were age matched and randomly grouped into continuous & control groups. The continuous group involved in an 8 weeks continuous training (60-79% HR reserve) of between 45minutes to 60 minutes, 3 times per week, while the control group remain sedentary. SBP, DBP, VO 2 max, serum Cr, body mass index (BMI), waist hip ratio (WHR) and percent (%) body fat. Analysis of covariance (ANCOVA) and Pearson correlation tests were used in data analysis. Results: Findings of the study revealed significant decreased effects of continuous training programme on SBP, DBP, Cr, BMI, WHR, % body fat and significant increase in VO 2 max at p< 0.05. Serum Cr is significantly and negatively correlated with SBP (-.335), DBP (.194), BMI (.268), WHR (-.258) and % body fat (-.190) at p<0.05. Conclusion:The present study demonstrated a rationale bases for the adjunct therapeutic role of moderate intensity continuous exercise training as a multitherapy in the down regulation of blood pressure, serum Cr, body size and body fat in hypertension.

Excessive consumption of alcohol is a leading cause of lifestyle-induced morbidity and mortality worldwide. Although long-term alcohol abuse has been shown to be detrimental to the liver, brain and many other organs, our understanding of the exact molecular mechanisms by which this occurs is still limited. In tissues, ethanol is metabolized to acetaldehyde (mainly by alcohol dehydrogenase and cytochrome p450 2E1) and subsequently to acetic acid by aldehyde dehydrogenases. Intracellular generation of free radicals and depletion of the antioxidant glutathione (GSH) are believed to be key steps involved in the cellular pathogenic events caused by ethanol. With continued excessive alcohol consumption, further tissue damage can result from the production of cellular protein and DNA adducts caused by accumulating ethanol-derived aldehydes. Much of our understanding about the pathophysiological consequences of ethanol metabolism comes from genetically-engineered mouse models of ethanol-induced tissue injury. In this review, we provide an update on the current understanding of important mouse models in which ethanol-metabolizing and GSH-synthesizing enzymes have been manipulated to investigate alcohol-induced disease.

Glutamate cysteine ligase catalytic subunit (Gclc) is the catalytic subunit for the glutamate-cysteine ligase (Gcl) enzyme. Gcl catalyzes the rate limiting step in glutathione (GSH) synthesis. Gclc is highly expressed in the developing eye. To define the regulatory role of Gclc in eye development, we developed a novel, Le-Cre transgene-driven, Gclc knockout mouse model. Gclc f/f /Le-Cre Tg/mice present with deformation of the retina, cornea, iris, and lens, consistent with a microphthalmia phenotype. Controlling for the microphthalmia phenotype of Gclc wt/wt /Le-Cre Tg/mice revealed that Gclc f/f /Le-Cre Tg/mice have a more severe microphthalmia phenotype. Thus, the loss of Gclc expression exacerbates the microphthalmia phenotype in Le-Cre mice.Gclc f/f /Le-Cre Tg/eyes present with reduced retinal and lens epithelium proliferation and increased lens cell death. Imaging mass spectrometry of ocular tissues revealed changes in the intensity and distribution of several lipid species and proteins in the retina and corneas of Gclc f/f /Le-Cre Tg/eyes. Lastly, using splice-blocking morpholinos and CRISPR/Cas9, we created two gclc knockdown zebrafish models, both of which display a microphthalmia phenotype. Combined, the mouse and zebrafish results indicate that, in chordates, Gclc has a conserved role in regulating eye development. In summary, these novel animal models are useful tools for elucidating the mechanisms involved in microphthalmia development.≈ 11% of the cases [1]. Currently, there is no cure for the severe loss of vision associated with microphthalmia. While surgical treatments exist, they only address the cosmetic abnormalities associated with microphthalmia [15]. However, recent research demonstrating the efficacy of nonsense suppression (inhibiting the effect of a nonsense mutation by pharmacologically increasing the likelihood of a near cognate aminoacyl-tRNA substitution) to rescue lens development when administered postnatally in a Pax6-deficient mouse model has provided hope that treatments for microphthalmia can be developed [16]. Clearly, a more complete understanding of the mechanisms regulating lens development should accelerate the discovery of preventative strategies and/or novel therapeutic treatments for microphthalmia. Glutathione (GSH), an intracellular antioxidant, is highly abundant in the eye, with concentrations of 20mM or more occurring in the lens cortex and epithelium [17, 18]. It is important for physiological detoxification of electrophiles and oxidants in the lens cortex and epithelium [19]. Through these functions, GSH maintains lens clarity and, as such, a decline in GSH levels is associated with cataract development [20, 21]. GSH biosynthesis involves a two-step enzymatic process [22] involving glutamate-cysteine ligase (GCL) followed by glutathione synthase (GSS). GCL, the rate limiting step in GSH synthesis, comprises a catalytic subunit (GCLC) and a modifier subunit (GCLM). Impaired GCLC or GCLM function limits GSH synthesis and reduces intracellular GSH concentrations. Th...