Angelica archengelica extract induced perturbation of rat skin and tight junctional protein (ZO-1) of HaCaT cells

Background and purpose of the study: Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells. Methods: Transepidermal water loss (TEWL) from the rat skin treated with different concentrations of AA-E was assessed by Tewameter. Scanning and Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin portions. The possibility of AA-E influence on the architecture of tight junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was investigated. Finally, the systemic delivery of repaglinide from the optimized transdermal formulation was investigated in rats. Results: The permeation of repaglinide across excised rat epidermis was 7-fold higher in the presence of AA-E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was found to perturb the lipid microconstituents in both excised and viable rat skin, although, the effect was less intense in the later. The enhanced permeation of repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for different periods was in concordance with the high TEWL values of similarly treated viable rat skin. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning Microscopy studies (CLSM) studies. The plasma concentration of repaglinide from transdermal formulation was maintained higher and for longer time as compared to oral administration of repaglinide. Major conclusion: Results suggest the overwhelming influence of Angelica archengelica in enhancing the percutaneous permeation of repaglinide to be mediated through perturbation of skin lipids and tight junction protein (ZO-1).

Noise and outlier removal from jet engine health signals using weighted FIR median hybrid filters

The removal of noise and outliers from measurement signals is a major problem in jet engine health monitoring. Topical measurement signals found in most jet engines include low rotor speed, high rotor speed. fuel flow and exhaust gas temperature. Deviations in these measurements from a baseline 'good' engine are often called measurement deltas and the health signals used for fault detection, isolation, trending and data mining. Linear filters such as the FIR moving average filter and IIR exponential average filter are used in the industry to remove noise and outliers from the jet engine measurement deltas. However, the use of linear filters can lead to loss of critical features in the signal that can contain information about maintenance and repair events that could be used by fault isolation algorithms to determine engine condition or by data mining algorithms to learn valuable patterns in the data, Non-linear filters such as the median and weighted median hybrid filters offer the opportunity to remove noise and gross outliers from signals while preserving features. In this study. a comparison of traditional linear filters popular in the jet engine industry is made with the median filter and the subfilter weighted FIR median hybrid (SWFMH) filter. Results using simulated data with implanted faults shows that the SWFMH filter results in a noise reduction of over 60 per cent compared to only 20 per cent for FIR filters and 30 per cent for IIR filters. Preprocessing jet engine health signals using the SWFMH filter would greatly improve the accuracy of diagnostic systems. (C) 2002 Published by Elsevier Science Ltd.

Design enhancement of the underwater noise control linings through a parsimonious parametric study

Control of sound transmission through the structure and reflection from the structure immersed in fluid media impose highly conflicting requirements on the design of the carpeted noise control linings. These requirements become even more stringent if the structure is expected to be moving with considerable speed particularly under intense hydrostatic pressure. Numerous configurations are possible for designing these linings. Therefore, in this paper, a few lining configurations are identified from the literature for parametric study so that the designer is provided with an environment to analyze and design the lining. A scheme of finite element analysis is used to analyze these linings for their acoustic performance. Commercial finite element software, NISA®, is used as a platform to develop a customized environment wherein design parameters of different configurations can be varied with consistency checks and generate the finite element meshes using the 8-noded hexahedral element. Four types of designs proposed and analysed here address the parameters of interest such as the echo reduction and the transmission loss. Study of the effect of different surface distributions of the cavities is carried out. Effect of static pressure on different designs is reported.

Ultrafast Raman loss spectroscopy (URLS): instrumentation and principle

In this paper, we report on the concept and the design principle of ultrafast Raman loss spectroscopy (URLS) as a structure-elucidating tool. URLS is an analogue of stimulated Raman scattering (SRS) but more sensitive than SRS with better signal-to-noise ratio. It involves the interaction of two laser sources, namely, a picosecond (ps) Raman pump pulse and a white-light (WL) continuum, with a sample, leading to the generation of loss signals on the higher energy (blue) side with respect to the wavelength of the Raman pump unlike the gain signal observed on the lower energy (red) side in SRS. These loss signals are at least 1.5 times more intense than the SRS signals. An experimental study providing an insight into the origin of this extra intensity in URLS as compared to SRS is reported. Furthermore, the very requirement of the experimental protocol for the signal detection to be on the higher energy side by design eliminates the interference from fluorescence, which appears on the red side. Unlike CARS, URLS signals are not precluded by the non-resonant background and, being a self-phase-matched process, URLS is experimentally easier. Copyright (C) 2011 John Wiley & Sons, Ltd.

Effect of gate-drain/source overlap on the noise in 90 nm N-channel metal oxide semiconductor field effect transistors

In this paper, we have studied the effect of gate-drain/source overlap (LOV) on the drain channel noise and induced gate current noise (SIg) in 90 nm N-channel metal oxide semiconductor field effect transistors using process and device simulations. As the change in overlap affects the gate tunneling leakage current, its effect on shot noise component of SIg has been taken into consideration. It has been shown that “control over LOV” allows us to get better noise performance from the device, i.e., it allows us to reduce noise figure, for a given leakage current constraint. LOV in the range of 0–10 nm is recommended for the 90 nm gate length transistors, in order to get the best performance in radio frequency applications.

Prediction of Breakout Noise from a Rectangular Duct with Compliant Walls

Breakout noise from HVAC ducts is important at low frequencies, and the coupling between the acoustic waves and the structural waves plays a critical role in the prediction of the transverse transmission loss. This paper describes the analytical calculation of breakout noise by incorporating three-dimensional effects along with the acoustical and structural wave coupling phenomena. The first step in the breakout noise prediction is to calculate the inside duct pressure field and the normal duct wall vibration by using the solution of the governing differential equations in terms of Green's function. The resultant equations are rearranged in terms of impedance and mobility, which results in a compact matrix formulation. The Green's function selected for the current problem is the cavity Green's function with modification of wave number in the longitudinal direction in order to incorporate the terminal impedance. The second step is to calculate the radiated sound power from the compliant duct walls by means of an ``equivalent unfolded plate'' model. The transverse transmission loss from the duct walls is calculated using the ratio of the incident power due to surface source inside the duct to the acoustic power radiated from the compliant duct walls. Analytical results are validated with the FE-BE numerical models.

Combined Electron Transfer Dissociation-Collision-Induced Dissociation Fragmentation in the Mass Spectrometric Distinction of Leucine, Isoleucine, and Hydroxyproline Residues in Peptide Natural Products

Distinctions between isobaric residues have been a major challenge in mass spectrometric peptide sequencing. Here, we propose a methodology for distinction among isobaric leucine, isoleucine, and hydroxyproline, a commonly found post-translationally modified amino acid with a nominal mass of 113 Da, through a combined electron transfer dissociation-collision-induced dissociation approach. While the absence of c and z(center dot) ions, corresponding to the Yyy-Xxx (Xxx = Leu, Ile, or Hyp) segment, is indicative of the presence of hydroxyproline, loss of isopropyl (Delta m = 43 Da) or ethyl radicals (Delta m = 29 Da), through collisional activation of z(center dot) radical ions, are characteristic of leucine or isoleucine, respectively. Radical migration processes permit distinctions even in cases where the specific e ions, corresponding to the Yyy-Leu or -Ile segments, are absent or of low intensity. This tandem mass spectrometric (MSn) method has been successfully implemented in a liquid chromatography MSn platform to determine the identity of 23 different isobaric residues from a mixture of five different peptides. The approach is convenient for distinction of isobaric residues from any crude peptide mixture, typically encountered in natural peptide libraries or proteomic analysis.

Dimethyl sulfoxide induced structural transformations and non-monotonic concentration dependence of conformational fluctuation around active site of lysozyme

Experimental studies have observed significant changes in both structure and function of lysozyme (and other proteins) on addition of a small amount of dimethyl sulfoxide (DMSO) in aqueous solution. Our atomistic molecular dynamic simulations of lysozyme in water-DMSO reveal the following sequence of changes on increasing DMSO concentration. (i) At the initial stage (around 5% DMSO concentration) protein's conformational flexibility gets markedly suppressed. From study of radial distribution functions, we attribute this to the preferential solvation of exposed protein hydrophobic residues by the methyl groups of DMSO. (ii) In the next stage (10-15% DMSO concentration range), lysozome partially unfolds accompanied by an increase both in fluctuation and in exposed protein surface area. (iii) Between 15-20% concentration ranges, both conformational fluctuation and solvent accessible protein surface area suddenly decrease again indicating the formation of an intermediate collapse state. These results are in good agreement with near-UV circular dichroism (CD) and fluorescence studies. We explain this apparently surprising behavior in terms of a structural transformation which involves clustering among the methyl groups of DMSO. (iv) Beyond 20% concentration of DMSO, the protein starts its final sojourn towards the unfolding state with further increase in conformational fluctuation and loss in native contacts. Most importantly, analysis of contact map and fluctuation near the active site reveal that both partial unfolding and conformational fluctuations are centered mostly on the hydrophobic core of active site of lysozyme. Our results could offer a general explanation and universal picture of the anomalous behavior of protein structure-function observed in the presence of cosolvents (DMSO, ethanol, tertiary butyl alcohol, dioxane) at their low concentrations. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3694268]

Strain induced phase transition in CdSe nanowires: Effect of size and temperature

Using all-atom molecular dynamics simulation, we have studied the effect of size and temperature on the strain induced phase transition of wurtzite CdSe nanowires. The wurtzite structure transforms into a five-fold coordinated structure under uniaxial strain along the c axis. Our results show that lower temperature and smaller size of the nanowires stabilize the five-fold coordinated phase which is not a stable structure in bulk CdSe. High reversibility of this transformation with a very small heat loss will make these nanowires suitable for building efficient nanodevices. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4734990]

On the basin-scale detection and attribution of human-induced climate change in monsoon precipitation and streamflow

Detecting and quantifying the presence of human-induced climate change in regional hydrology is important for studying the impacts of such changes on the water resources systems as well as for reliable future projections and policy making for adaptation. In this article a formal fingerprint-based detection and attribution analysis has been attempted to study the changes in the observed monsoon precipitation and streamflow in the rain-fed Mahanadi River Basin in India, considering the variability across different climate models. This is achieved through the use of observations, several climate model runs, a principal component analysis and regression based statistical downscaling technique, and a Genetic Programming based rainfall-runoff model. It is found that the decreases in observed hydrological variables across the second half of the 20th century lie outside the range that is expected from natural internal variability of climate alone at 95% statistical confidence level, for most of the climate models considered. For several climate models, such changes are consistent with those expected from anthropogenic emissions of greenhouse gases. However, unequivocal attribution to human-induced climate change cannot be claimed across all the climate models and uncertainties in our detection procedure, arising out of various sources including the use of models, cannot be ruled out. Changes in solar irradiance and volcanic activities are considered as other plausible natural external causes of climate change. Time evolution of the anthropogenic climate change ``signal'' in the hydrological observations, above the natural internal climate variability ``noise'' shows that the detection of the signal is achieved earlier in streamflow as compared to precipitation for most of the climate models, suggesting larger impacts of human-induced climate change on streamflow than precipitation at the river basin scale.

A Huber-loss-driven clustering technique and its application to robust cell detection in confocal microscopy images

We address the problem of detecting cells in biological images. The problem is important in many automated image analysis applications. We identify the problem as one of clustering and formulate it within the framework of robust estimation using loss functions. We show how suitable loss functions may be chosen based on a priori knowledge of the noise distribution. Specifically, in the context of biological images, since the measurement noise is not Gaussian, quadratic loss functions yield suboptimal results. We show that by incorporating the Huber loss function, cells can be detected robustly and accurately. To initialize the algorithm, we also propose a seed selection approach. Simulation results show that Huber loss exhibits better performance compared with some standard loss functions. We also provide experimental results on confocal images of yeast cells. The proposed technique exhibits good detection performance even when the signal-to-noise ratio is low.

Narrowing of resonances in electromagnetically induced transparency and absorption using a Laguerre-Gaussian control beam

We study the phenomenon of electromagnetically induced transparency and absorption (EITA) using a control laser with a Laguerre-Gaussian (LG) profile instead of the usual Gaussian profile, and observe significant narrowing of the resonance widths. Aligning the probe beam to the central hole in the doughnut-shaped LG control beam allows simultaneously a strong control intensity required for high signal-to-noise ratio and a low intensity in the probe region required to get narrow resonances. Experiments with an expanded Gaussian control and a second-order LG control show that transit time and orbital angular momentum do not play a significant role. This explanation is borne out by a density-matrix analysis with a radially varying control Rabi frequency. We observe these resonances using degenerate two-level transitions in the D-2 line of Rb-87 in a room temperature vapor cell, and an EIA resonance with width up to 20 times below the natural linewidth for the F = 2 -> F' = 3 transition. Thus the use of LG beams should prove advantageous in all applications of EITA and other kinds of pump-probe spectroscopy as well.

Noise tolerance under risk minimization

In this paper, we explore noise-tolerant learning of classifiers. We formulate the problem as follows. We assume that there is an unobservable training set that is noise free. The actual training set given to the learning algorithm is obtained from this ideal data set by corrupting the class label of each example. The probability that the class label of an example is corrupted is a function of the feature vector of the example. This would account for most kinds of noisy data one encounters in practice. We say that a learning method is noise tolerant if the classifiers learnt with noise-free data and with noisy data, both have the same classification accuracy on the noise-free data. In this paper, we analyze the noise-tolerance properties of risk minimization (under different loss functions). We show that risk minimization under 0-1 loss function has impressive noise-tolerance properties and that under squared error loss is tolerant only to uniform noise; risk minimization under other loss functions is not noise tolerant. We conclude this paper with some discussion on the implications of these theoretical results.

Microglia play a major role in direct viral-induced demyelination

Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.

Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1

In this study we determined the molecular mechanisms of how homocysteine differentially affects receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) synthesis in the bone. The results showed that oxidative stress induced by homocysteine deranges insulin-sensitive FOXO1 and MAP kinase signaling cascades to decrease OPG and increase RANKL synthesis in osteoblast cultures. We observed that downregulation of insulin/FOXO1 and p38 MAP kinase signaling mechanisms due to phosphorylation of protein phosphatase 2 A (PP2A) was the key event that inhibited OPG synthesis in homocysteine-treated osteoblast cultures. siRNA knockdown experiments confirmed that FOXO1 is integral to OPG and p38 synthesis. Conversely homocysteine increased RANKL synthesis in osteoblasts through c-Jun/JNK MAP kinase signaling mechanisms independent of FOXO1. In the rat bone milieu, high-methionine diet-induced hyperhomocysteinemia lowered FOXO1 and OPG expression and increased synthesis of proresorptive and inflammatory cytokines such as RANKL, M-CSF, IL-1 alpha, IL-1 beta, G-CSF, GM-CSF, MIP-1 alpha, IFN-gamma, IL-17, and TNF-alpha. Such pathophysiological conditions were exacerbated by ovariectomy. Lowering the serum homocysteine level by a simultaneous supplementation with N-acetylcysteine improved OPG and FOXO1 expression and partially antagonized RANKL and proresorptive cytokine synthesis in the bone milieu. These results emphasize that hyperhomocysteinemia alters the redox regulatory mechanism in the osteoblast by activating PP2A and deranging FOXO1 and MAPK signaling cascades, eventually shifting the OPG:RANKL ratio toward increased osteoclast activity and decreased bone quality (C) 2013 Elsevier Inc. All rights reserved.