Sensitivity analysis for shape perturbation of cavity or internal crack using BIE and adjoint variable approach

This paper deals with the application of the adjoint variable approach to sensitivity analysis of objective functions used for defect detection from knowledge of supplementary boundary data, in connection with the use of BIE/BEM formulations for the relevant forward problem. The main objective is to establish expressions for crack shape sensitivity, based on the adjoint variable approach, that are suitable for BEM implementation. In order to do so, it is useful to consider first the case of a cavity defect, for which such boundary-only sensitivity expressions are obtained for general initial geometry and shape perturbations. The analysis made in the cavity defect case is then seen to break down in the limiting case of a crack. However, a closer analysis reveals that sensitivity formulas suitable for BEM implementation can still be established. First, particular sensitivity formulas are obtained for special shape transformations (translation, rotation or expansion of the crack) for either two- or three-dimensional geometries which, except for the case of crack expansion together with dynamical governing equations, are made only of surface integrals (three-dimensional geometries) or line integrals (two-dimensional geometries). Next, arbitrary shape transformations are accommodated by using an additive decomposition of the transformation velocity over a tubular neighbourhood of the crack front, which leads to sensitivity formulas. This leads to sensitivity formulas involving integrals on the crack, the tubular neighbourhood and its boundary. Finally, the limiting case of the latter results when the tubular neighbourhood shrinks around the crack front is shown to yield a sensitivity formula involving the stress intensity factors of both the forward and the adjoint solutions. Classical path-independent integrals are recovered as special cases. The main exposition is done in connection with the scalar transient wave equation. The results are then extended to the linear time-domain elastodynamics framework. Linear static governing equations are contained as obvious special cases. Numerical results for crack shape sensitivity computation are presented for two-dimensional time-domain elastodynamics

Sound scattering by live zooplankton and micronekton : empirical studies with a dual-beam acoustical system

Author Posting. © Acoustical Society of America, 1990. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 88 (1990): 2346-2360, doi:10.1121/1.400077.Measurements and analyses are presented of the backscattering of 420-kHz sound by 43 individual animals of representative zooplanktonic and micronektonic taxa. Direct measurements of an individual's target strength were made with a commercial dual-beam sonar system in an enclosure filled with filtered seawater deployed off a dock at Friday Harbor, Washington. The dependence of target stengths upon individual length, wet weight, and dry weight was investigated. In addition, the ``target strength'' and statistical variations of echo amplitude due to variations in shape and orientation of the organism were compared with acoustic scattering models involving different shapes (the general shapes of the sphere, and straight and uniformly bent finite cylinders were used along with attempts to take into account roughness). It was found that: (1) backscattering cross sections are proportional to volume of the organisms rather than area as would be predicted by a sphere scattering model, (2) mean target strength based on average backscattering crossection is best described by the bent cylinder model whose modal series solution is truncated, and (3) the fluctuations of the echo amplitudes are well described by the Rice probability density function whose shape parameter is related to the randomly rough straight cylinder model. These extensive studies showed conclusively that the elongated animals scattered sound more like elongated targets than spherical ones, thus demonstrating the need for models more sophisticated than the spherical ones routinely used to date. The data and model analyses provide a basis for devising future acoustical data acquisition and processing techniques for bioacoustical field studies.This research was supported by the Oceanic Biology and Ocean Acoustics Programs of the Office of Naval Research Contract Nos. N00014-87-K-007 and N00014-89-J-1729, respectively and the National Science Foundation Grant No. OCE-8709962

Attenuation of Diabetic Nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats with a Combination of Chinese Herbs (Tangshen Formula)

Diabetic nephropathy is one of the most significant microvascular complications in patients with type 2 diabetics. The concise mechanism of diabetic nephropathy is unknown and there is no successful treatment. The objective of study was to investigate effects of Chinese herbs (Tangshen Formula) on diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats and LETO rats were divided into four groups: LETO control, OLETF diabetics, OLETF diabetics treated with Tangshen Formula, and OLETF diabetics treated with Monopril. Body weight, blood glucose, and 24 h urinary proteins were measured once every four weeks. Blood samples and kidney tissues were obtained for analyses of total cholesterol, triglyceride, whole blood viscosity, plasma viscosity, and pathohistological examination at 36 and 56 weeksrespectively. Untreated OLETF rats displayed diabetic nephropathy over the study period. Treatment of OLETF rats with Tangshen Formula attenuated the increases in blood glucose, body weight, 24 h urinary protein content, serum total cholesterol, whole blood viscosity and plasma viscosity at certain time. Treatment with Tangshen Formula also reduced glomerulosclerotic index and interstitial fibrotic index seen in OLETF rats. In conclusion, Tangshen Formula could attenuate the development of diabetic nephropathy in OLETF rat diabetic model

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

The liver is important in the biotransformation of various drugs, where hepatic transporters facilitate uptake and excretion. Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery, and the developing oxidative stress can lead to graft failure. We used intravital multiphoton tomography, with fluorescence lifetime imaging, to characterize metabolic damage associated with hepatic I/R injury and to model the distribution of fluorescein as a measure of liver function. In addition to measuring a significant increase in serum alanine transaminase levels, characteristic of hepatic I/R injury, a decrease in the averaged weighted lifetime of reduced nicotinamide adenine dinucleotide phosphate was observed, which can be attributed to a changed metabolic redox state of the hepatocytes. I/R injury was associated with delayed uptake and excretion of fluorescein and elevated area-under-the-curve within the hepatocytes compared to sham (i.e., untreated control) as visualized and modeled using images recorded by intravital multiphoton tomography. High-performance liquid chromatography analysis showed no differences in plasma or bile concentrations of fluorescein. Finally, altered fluorescein distribution was associated with acute changes in the expression of liver transport proteins. In summary, multiphoton intravital imaging is an effective approach to measure liver function and is more sensitive in contrasting the impact of I/R injury than measuring plasma and bile concentrations of fluorescein

Hematopoietic Lineage Transcriptome Stability and Representation in PAXgene™ Collected Peripheral Blood Utilising SPIA Single-Stranded cDNA Probes for Microarray

Peripheral blood as a surrogate tissue for transcriptome profiling holds great promise for the discovery of diagnostic and prognostic disease biomarkers, particularly when target tissues of disease are not readily available. To maximize the reliability of gene expression data generated from clinical blood samples, both the sample collection and the microarray probe generation methods should be optimized to provide stabilized, reproducible and representative gene expression profiles faithfully representing the transcriptional profiles of the constituent blood cell types present in the circulation. Given the increasing innovation in this field in recent years, we investigated a combination of methodological advances in both RNA stabilisation and microarray probe generation with the goal of achieving robust, reliable and representative transcriptional profiles from whole blood. To assess the whole blood profiles, the transcriptomes of purified blood cell types were measured and compared with the global transcriptomes measured in whole blood. The results demonstrate that a combination of PAXgene™ RNA stabilising technology and single-stranded cDNA probe generation afforded by the NuGEN Ovation RNA amplification system V2™ enables an approach that yields faithful representation of specific hematopoietic cell lineage transcriptomes in whole blood without the necessity for prior sample fractionation, cell enrichment or globin reduction. Storage stability assessments of the PAXgene™ blood samples also advocate a short, fixed room temperature storage time for all PAXgene™ blood samples collected for the purposes of global transcriptional profiling in clinical studies

Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats

Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery. In orthotopic transplantation, the donor liver is exposed to periods of ischemia and when oxygenated blood is reintroduced to the liver, oxidative stress may develop and lead to graft failure. The aim of this project was to investigate whether noninvasive multiphoton and fluorescence lifetime imaging microscopy, without external markers, were useful in detecting early liver damage caused by I/R injury. Localized hepatic ischemia was induced in rats for 1 h followed by 4 h reperfusion. Multiphoton and fluorescence lifetime imaging microscopy was conducted prior to ischemia and up to 4 h of reperfusion and compared to morphological and biochemical assessment of liver damage. Liver function was significantly impaired at 2 and 4 h of reperfusion. Multiphoton microscopy detected liver damage at 1 h of reperfusion, manifested by vacuolated cells and heterogeneous spread of damage over the liver. The damage was mainly localized in the midzonal region of the liver acinus. In addition, fluorescence lifetime imaging showed a decrease in cellular metabolic activity. Multiphoton and fluorescence lifetime imaging microscopy detected evidence of early I/R injury both structurally and functionally. This provides a simple noninvasive technique useful for following progressive liver injury without external markers. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3647597

Exposures to Airborne Particulate Matter and Adverse Perinatal Outcomes: A Biologically Plausible Mechanistic Framework for Exploring Potential Effect Modification by Nutrition

OBJECTIVES: The specific objectives are threefold: to describe the biologically plausible mechanistic pathways by which exposure to particulate matter (PM) may lead to the adverse perinatal outcomes of low birth weight (LBW), intrauterine growth retardation (IUGR), and preterm delivery (PTD); review the evidence showing that nutrition affects the biologic pathways; and explain the mechanisms by which nutrition may modify the impact of PM exposure on perinatal outcomes. METHODS: We propose an interdisciplinary conceptual framework that brings together maternal and infant nutrition, air pollution exposure assessment, and cardiopulmonary and perinatal epidemiology. Five possible albeit not exclusive biologic mechanisms have been put forth in the emerging environmental sciences literature and provide corollaries for the proposed framework. CONCLUSIONS: Protecting the environmental health of mothers and infants remains a top global priority. The existing literature indicates that the effects of PM on LBW, PTD, and IUGR may manifest through the cardiovascular mechanisms of oxidative stress, inflammation, coagulation, endothelial function, and hemodynamic responses. PM exposure studies relating mechanistic pathways to perinatal outcomes should consider the likelihood that biologic responses and adverse birth outcomes may be derived from both PM and non-PM sources (e.g., nutrition). In the concluding section, we present strategies for empirically testing the proposed model and developing future research efforts

Pharmaceutical Characterization of MyoNovin, a Novel Skeletal Muscle Regenerator: in silico, in vitro and in vivo Studies.

MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin. In vitro cardiotoxicity was assessed using human cardiomyocytes (RL-14) while effects on CYP3A4 metabolic enzyme and antioxidant activity were examined using commercial kits. A novel HPLC assay was developed to measure MyoNovin concentration in serum, and delineate initial pharmacokinetic and acute toxicity after intravenous administration (20 mg/kg) to male Sprague-Dawley rats. MyoNovin showed relatively high lipophilicity with a LogP value of 3.49, a 20-fold higher skin permeability (19.89 cm/s*107) compared to guaifenesin (0.66 cm/s*107), and ~10-fold higher effective jejunal permeability (2.24 cm/s*104) compared to guaifenesin (0.26 cm/s*104). In vitro, MyoNovinwas not cytotoxic to cardiomyocytes at concentrations below 8 μM and did not inhibit CYP3A4 or show antioxidant activity. In vivo, MyoNovin had a short half-life (t1/2) of 0.16 h, and a volume of distribution Vss of 0.62 L/kg. Biomarkers of MyoNovincardiac and renal toxicity did not differ significantly from baseline control levels. The predicted high lipophilicity and skin permeability of MyoNovin render it a potential candidate for transdermal administration while its favourable intestinal permeation suggests it may be suitable for oral administration. Pharmacokinetics following IV administration of MyoNovin were delineated for the first time in a rat model. Preliminary single 20 mg/kg dose assessment of MyoNovin suggest no influenceon cardiac troponin or β-N-Acetylglucosaminidase. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page