Interferon-gamma induced cell death: Regulation and contributions of nitric oxide, cJun N-terminal kinase, reactive oxygen species and peroxynitrite

Interferon-gamma (Ifn gamma), a known immunomodulatory cytokine, regulates cell proliferation and survival. In this study, the mechanisms leading to the selective susceptibility of some tumor cells to Ifn gamma were deciphered. Seven different mouse tumor cell lines tested demonstrated upregulation of MHC class I to variable extents with Ifn gamma; however, only the cell lines, H6 hepatoma and L929 fibrosarcoma, that produce higher amounts of nitric oxide (NO) and reactive oxygen species (ROS) are sensitive to Ifn gamma-induced cell death. NO inhibitors greatly reduce Ifn gamma-induced ROS; however, ROS inhibitors did not affect the levels of Ifn gamma-induced NO, demonstrating that NO regulates ROS. Consequently, NO inhibitors are more effective, compared to ROS inhibitors, in reducing Ifn gamma-induced cell death. Further analysis revealed that Ifn gamma induces peroxynitrite and 3-nitrotyrosine amounts and a peroxynitrite scavenger, FeTPPS, reduces cell death. Ifn gamma treatment induces the phosphorylation of c-jun N-terminal kinase (Jnk) in H6 and L929 but not CT26, a colon carcinoma cell line, which is resistant to Ifn gamma-mediated death. Jnk activation downstream to NO leads to induction of ROS, peroxynitrite and cell death in response to Ifn gamma. Importantly, three cell lines tested, i.e. CT26, EL4 and Neuro2a, that are resistant to cell death with Ifn gamma alone become sensitive to the combination of Ifn gamma and NO donor or ROS inducer in a peroxynitrite-dependent manner. Overall, this study delineates the key roles of NO as the initiator and Jnk, ROS, and peroxynitrite as the effectors during Ifn gamma-mediated cell death. The implications of these findings in the Ifn gamma-mediated treatment of malignancies are discussed. (C) 2014 Elsevier B.V. All rights reserved.

Finite element analysis of free vibration of the delaminated composite plate with variable kinematic multilayered plate elements

Composite laminates are prone to delamination. Implementation of delamination in the Carrera Unified Formulation frame work using nine noded quadrilateral MITC9 element is discussed in this article. MITC9 element is devoid of shear locking and membrane locking. Delaminated as well as healthy structure is analyzed for free mode vibration. The results from the present work are compared with the available experimental or/and research article or/and the three dimensional finite element simulations. The effect of different kinds and different percentages of area of delamination on the first three natural frequencies of the structure is discussed. The presence of open-mode delamination mode shape for large delaminations within the first three natural frequencies is discussed. Also, the switching of places between the second bending mode, with that of the first torsional mode frequency is discussed. Results obtained from different ordered theories are compared in the presence of delamination. Advantage of layerwise theories as compared to equivalent single layer theories for very large delaminations is stated. The effect of different kinds of delamination and their effect on the second bending and first torsional mode shape is discussed. (C) 2014 Elsevier Ltd. All rights reserved.

Hot deformation behaviour and microstructure control in AlCrCuNiFeCo high entropy alloy

An AlCrCuNiFeCo high entropy alloy (HEA), which has simple face centered cubic (FCC) and body centered cubic (BCC) solid solution phases as the microstructural constituents, was processed and its high temperature deformation behaviour was examined as a function of temperature (700-1030 degrees C) and strain rate (10(-3)-10(-1) s(-1)), so as to identify the optimum thermo-mechanical processing (TMP) conditions for hot working of this alloy. For this purpose, power dissipation efficiency and deformation instability maps utilizing that the dynamic materials model pioneered by Prasad and co-workers have been generated and examined. Various deformation mechanisms, which operate in different temperature-strain rate regimes, were identified with the aid of the maps and complementary microstructural analysis of the deformed specimens. Results indicate two distinct deformation domains within the range of experimental conditions examined, with the combination of 1000 degrees C/10(-3) s(-1) and 1030 degrees C/10(-2) s(-1) being the optimum for hot working. Flow instabilities associated with adiabatic shear banding, or localized plastic flow, and or cracking were found for 700-730 degrees C/10(-3)-10(-1) s(-1) and 750-860 degrees C/10(-1.4)-10(-1) s(-1) combinations. A constitutive equation that describes the flow stress of AlCrCuNiFeCo alloy as a function of strain rate and deformation temperature was also determined. (C) 2014 Elsevier Ltd. All rights reserved.

Diffusion on a rugged energy landscape with spatial correlations

Rugged energy landscapes find wide applications in diverse fields ranging from astrophysics to protein folding. We study the dependence of diffusion coefficient (D) of a Brownian particle on the distribution width (epsilon) of randomness in a Gaussian random landscape by simulations and theoretical analysis. We first show that the elegant expression of Zwanzig Proc. Natl. Acad. Sci. U.S.A. 85, 2029 (1988)] for D(epsilon) can be reproduced exactly by using the Rosenfeld diffusion-entropy scaling relation. Our simulations show that Zwanzig's expression overestimates D in an uncorrelated Gaussian random lattice - differing by almost an order of magnitude at moderately high ruggedness. The disparity originates from the presence of ``three-site traps'' (TST) on the landscape - which are formed by the presence of deep minima flanked by high barriers on either side. Using mean first passage time formalism, we derive a general expression for the effective diffusion coefficient in the presence of TST, that quantitatively reproduces the simulation results and which reduces to Zwanzig's form only in the limit of infinite spatial correlation. We construct a continuous Gaussian field with inherent correlation to establish the effect of spatial correlation on random walk. The presence of TSTs at large ruggedness (epsilon >> k(B)T) gives rise to an apparent breakdown of ergodicity of the type often encountered in glassy liquids. (C) 2014 AIP Publishing LLC.

An experimental study on loading rate effect on acoustic emission based b-values related to reinforced concrete fracture

This article reports on analysis of fracture processes in reinforced concrete (RC) beams with acoustic emission (AE) technique. An emphasis was given to study the effect of loading rate on variation in AE based b-values with the development of cracks in RC structures. RC beams of length 3.2 m were tested under load control at a rate of 4 kN/s, 5 kN/s and 6 kN/s and the b-value analysis available in seismology was used to study the fracture process in RC structures. Moreover, the b-value is related to the strain in steel to assess the damage state. It is observed that when the loading rate is higher, quick cracking development lead to rapid fluctuations and drops in the b-values. Also it is observed that concrete behaves relatively more brittle at higher loading rates (or at higher strain rates). The average b-values are lower as a few but larger amplitudes of AE events occur in contrast to more number of low amplitude AE events occur at low loading rates (or at low strain rates). (C) 2014 Elsevier Ltd. All rights reserved.

Biodegradation of acrylamide by acrylamidase from Stenotrophomonas acidaminiphila MSU12 and analysis of degradation products by MALDI-TOF and HPLC

The present study examines an improved detoxification and rapid biological degradation of toxic pollutant acrylamide using a bacterium. The acrylamide degrading bacterium was isolated from the soil followed by its screening to know the acrylamide degrading capability. The minimal medium containing acrylamide (30 mM) served as a sole source of carbon and nitrogen for their active growth. The optimization of three different factors was analyzed by using Response Surface Methodology (RSM). The bacteria actively degraded the acrylamide at a temperature of 32 degrees C, with a maximum growth at 30 mM substrate (acrylamide) concentration at a pH of 7.2. The acrylamidase activity and degradation of acrylamide was determined by High Performance Liquid Chromatography (HPLC) and Matrix Assisted Laser Desorption and Ionization Time of Flight mass spectrometer (MALDI-TOF). Based on 168 rRNA analysis the selected strain was identified as Gram negative bacilli Stenotrophomonas acidaminiphila MSU12. The acrylamidase was isolated from bacterial extract and was purified by HPLC, whose mass spectrum showed a molecular mass of 38 kDa. (C) 2014 Elsevier Ltd. All rights reserved.

Transverse orthotropic elastic moduli of bundled coated thin elliptical tubes

Light weight structures with tailored mechanical properties have evolved beyond regular hexagonal/circular honeycomb topology. For applications which demand anisotropic mechanical properties, elliptical-celled structures offer interesting features. This paper characterizes the anisotropic in-plane elastic response of coated thin elliptical tubes in different array patterns viz, close-packed, diagonal and rectangular patterns under compression. This paper also extends earlier works on elliptical close-packed structure to a more general case of coated tubes. Theoretical framework using thin ring theory provides formulae in terms of geometric and material parameters. These are compared with a series of FE simulations using contact elements. The FE results are presented as graphs to aid in design. (C) 2014 Elsevier Ltd. All rights reserved.

The WNT Signaling Pathway Contributes to Dectin-1-Dependent Inhibition of Toll-Like Receptor-Induced Inflammatory Signature

Macrophages regulate cell fate decisions during microbial challenges by carefully titrating signaling events activated by innate receptors such as dectin-1 or Toll-like receptors (TLRs). Here, we demonstrate that dectin-1 activation robustly dampens TLR-induced proinflammatory signature in macrophages. Dectin-1 induced the stabilization of beta-catenin via spleen tyrosine kinase (Syk)-reactive oxygen species (ROS) signals, contributing to the expression of WNT5A. Subsequently, WNT5A-responsive protein inhibitors of activated STAT (PIAS-1) and suppressor of cytokine signaling 1 (SOCS-1) mediate the downregulation of IRAK-1, IRAK-4, and MyD88, resulting in decreased expression of interleukin 12 (IL-12), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha). In vivo activation of dectin-1 with pathogenic fungi or ligand resulted in an increased bacterial burden of Mycobacteria, Klebsiella, Staphylococcus, or Escherichia, with a concomitant decrease in TLR-triggered proinflammatory cytokines. All together, our study establishes a new role for dectin-1-responsive inhibitory mechanisms employed by virulent fungi to limit the proinflammatory environment of the host.

Glycosidic bond hydrolysis in septanosides: a comparison of mono-, di-, and 2-chloro-2-deoxy-septanosides

A kinetic study of the hydrolytic stabilities of mono-, di-, and 2-chloro-2-deoxy septanosides, under acid-catalysis, is reported herein. A comparison of mono-and diseptanosides, shows that the glycosidic bond in the disaccharide is more stable than the monosaccharide. Further the glycosidic bond at the reducing end hydrolyzes almost twice as faster than that of the non-reducing end of the disaccharide. 2-Chloro-2-deoxy septanoside is found to be the most stable and its glycosidic bond hydrolysis occurs at elevated temperatures only. The orientation of the exo-cyclic hydroxymethyl group and the inductive effect are suggested to play a role in the rates of hydrolysis. (C) 2014 Elsevier Ltd. All rights reserved.

Comparison of the photocatalytic degradation of trypan blue by undoped and silver-doped zinc oxide nanoparticles

Zinc oxide (ZnO) and silver doped zinc oxide (ZnO:Ag) nanoparticles were prepared using nitrates of zinc and silver as oxidizers and ethylene diaminetetraacetic acid (EDTA) as a fuel via low-temperature combustion synthesis (LCS) at 500 degrees C. X-ray diffraction (XRD) pattern indicates the presence of silver in the hexagonal wurtzite structure of ZnO. Fourier transform infrared (FTIR) spectrum indicates the presence of Ag-Zn-O stretching vibration at 510 cm(-1). Transmission electron microscopy (TEM) images shows that the average particle size of ZnO and ZnO:Ag nanoparticles were found to be 58 nm and 52 nm, respectively. X-ray photoelectron spectroscopy (XPS) data clearly indicates the presence of Ag in ZnO crystal lattice. The above characterization techniques indicate that the incorporation of silver affects the structural and optical properties of ZnO nanoparticles. ZnO:Ag nanoparticles exhibited 3% higher photocatalytic efficiency than pure ZnO nanoparticles. ZnO:Ag nanoparticles show better photocatalytic activity for the degradation of trypan blue (TrB) compared to undoped ZnO nanoparticles. (C) 2014 Elsevier Ltd. All rights reserved.

On the quality of hydrogenated amorphous silicon deposited by sputtering

Amorphous hydrogenated silicon (a-Si:H) is well-known material in the global semiconductor industry. The quality of the a-Si:H films is generally decided by silicon and hydrogen bonding configuration (Si-H-x, x=1,2) and hydrogen concentration (C-H). These quality aspects are correlated with the plasma parameters like ion density (N-i) and electron temperature (T-e) of DC, Pulsed DC (PDC) and RF plasmas during the sputter-deposition of a-Si:H thin films. It was found that the N-i and T-e play a major role in deciding Si-H-x bonding configuration and the C-H value in a-Si:H films. We observed a trend in the variation of Si-H and Si-H-2 bonding configurations, and C-H in the films deposited by DC, Pulsed DC and RF reactive sputtering techniques. Ion density and electron energy are higher in RF plasma followed by PDC and DC plasma. Electrons with two different energies were observed in all the plasmas. At a particular hydrogen partial pressure, RF deposited films have higher C-H followed by PDC and then DC deposited films. The maximum energy that can be acquired by the ions was found to be higher in RF plasma. Floating potential (V-f) is more negative in DC plasma, whereas, plasma potential (V-p) is found to be more positive in RF plasma. (C) 2014 Elsevier Ltd. All rights reserved.

A bottom-up approach for optimization of friction stir processing parameters; a study on aluminium 2024-T3 alloy

Friction stir processing (FSP) is emerging as one of the most competent severe plastic deformation (SPD) method for producing bulk ultra-fine grained materials with improved properties. Optimizing the process parameters for a defect free process is one of the challenging aspects of FSP to mark its commercial use. For the commercial aluminium alloy 2024-T3 plate of 6 mm thickness, a bottom-up approach has been attempted to optimize major independent parameters of the process such as plunge depth, tool rotation speed and traverse speed. Tensile properties of the optimum friction stir processed sample were correlated with the microstructural characterization done using Scanning Electron Microscope (SEM) and Electron Back-Scattered Diffraction (EBSD). Optimum parameters from the bottom-up approach have led to a defect free FSP having a maximum strength of 93% the base material strength. Micro tensile testing of the samples taken from the center of processed zone has shown an increased strength of 1.3 times the base material. Measured maximum longitudinal residual stress on the processed surface was only 30 MPa which was attributed to the solid state nature of FSP. Microstructural observation reveals significant grain refinement with less variation in the grain size across the thickness and a large amount of grain boundary precipitation compared to the base metal. The proposed experimental bottom-up approach can be applied as an effective method for optimizing parameters during FSP of aluminium alloys, which is otherwise difficult through analytical methods due to the complex interactions between work-piece, tool and process parameters. Precipitation mechanisms during FSP were responsible for the fine grained microstructure in the nugget zone that provided better mechanical properties than the base metal. (C) 2014 Elsevier Ltd. All rights reserved.

Covalent assembly-disassembly of poly(ether imine) dendritic macromolecular monomers and megamers

Poly(ether imine) dendritic macromolecules were undertaken to study the reversible dendrimer monomer-megamer assembly-disassembly in aqueous solutions. Synthesis of thiol functionalized poly(ether imine) (PETIM) dendrimers and their covalent aggregation behavior in the aqueous solution of ethanol/water (2:1) is demonstrated. The dendritic megamers were characterized using microscopic techniques. Kinetics of the aggregation behavior was followed using turbidity measurements, light-scattering and atomic force microscopic techniques. Inherent luminescence behavior of PETIM dendrimer monomers was retained in the dendrimer megamers also, which allowed visualization of the megamers through confocal microscopy. Extent of thiol functionalities that remained after the megamer assembly was estimated through Ellman's assay. Subsequent to megamer assembly, disassembly of megamers to dendrimer monomers was conducted, using dithiothreitol reagent. Water-insoluble sudan I dye was encapsulated in dendrimer megamer and subsequent release profile was assessed during the disassembly in aqueous solutions. The studies were conducted using first, second and third generations, representing 4, 8 and 16 sulfhydryl groups at their peripheries of dendrimers, respectively. (C) 2014 Elsevier Ltd. All rights reserved.

The effect of Cu addition on the thermoelectric properties of Cu2CdGeSe4

Recently, research in copper based quaternary chalcogenide materials has focused on the study of thermoelectric properties due to the complexity in the crystal structure. In the present work, stoichiometric quaternary chalcogenide compounds Cu2+xCd1-x,GeSe4 (x = 0, 0.025, 0.05, 0.075, 0.1, 0.125) were prepared by solid state synthesis. The powder X-ray diffraction patterns of all the samples showed a tetragonal crystal structure with the space group I-42m of the main phase, whereas the samples with x = 0 and x = 0.025 revealed the presence of an orthorhombic phase in addition to the main phase as confirmed by Rietveld analysis. The elemental composition of all the samples characterized by Electron Probe Micro Analyzer showed a slight deviation from the nominal composition. The transport properties were measured in the temperature range of 300 K-723 K. The electrical conductivity of all the samples increased with increasing Cu content due to the enhancement of the hole concentration caused by the substitution of Cd (divalent) by Cu (monovalent). The positive Seebeck coefficient of all the samples in the entire temperature ranges indicates that holes are the majority carriers. The Seebeck coefficient of all the samples decreased with increasing Cu content and showed a reverse trend to the electrical conductivity. The total thermal conductivity of all the samples decreased with increasing temperature which was dominated by the lattice contribution. The maximum figure of merit ZT = 0.42 at 723 K was obtained for the compound Cu2.1Cd0.9GeSe4. (C) 2014 Elsevier Ltd. All rights reserved.

Return levels of hydrologic droughts under climate change

Developments in the statistical extreme value theory, which allow non-stationary modeling of changes in the frequency and severity of extremes, are explored to analyze changes in return levels of droughts for the Colorado River. The transient future return levels (conditional quantiles) derived from regional drought projections using appropriate extreme value models, are compared with those from observed naturalized streamflows. The time of detection is computed as the time at which significant differences exist between the observed and future extreme drought levels, accounting for the uncertainties in their estimates. Projections from multiple climate model-scenario combinations are considered; no uniform pattern of changes in drought quantiles is observed across all the projections. While some projections indicate shifting to another stationary regime, for many projections which are found to be non-stationary, detection of change in tail quantiles of droughts occurs within the 21st century with no unanimity in the time of detection. Earlier detection is observed in droughts levels of higher probability of exceedance. (C) 2014 Elsevier Ltd. All rights reserved.