Curcumin Increases the Pathogenicity of Salmonella enterica Serovar Typhimurium in Murine Model

Curcumin has gained immense importance for its vast therapeutic and prophylactic applications. Contrary to this, our study reveals that it regulates the defense pathways of Salmonella enterica serovar Typhimurium ( S. Typhimurium) to enhance its pathogenicity. In a murine model of typhoid fever, we observed higher bacterial load in Peyer's,patches, mesenteric lymph node, spleen and liver, when infected with curcumin-treated Salmonella. Curcumin increased the resistance of S. Typhimurium against antimicrobial agents like antimicrobial peptides, reactive oxygen and nitrogen species. This increased tolerance might be attributed to the up-regulation of genes involved in resistance against antimicrobial peptides - pmrD and pmrHFIJKLM and genes with antioxidant function - mntH, sodA and sitA. We implicate that iron chelation property of curcumin have a role in regulating mntH and sitA. Interestingly, we see that the curcumin-mediated modulation of pmr genes is through the PhoPQ regulatory system. Curcumin downregulates SPI1 genes, required for entry into epithelial cells and upregulates SPI2 genes required to intracellular survival. Since it is known that the SPI1 and SPI2 system can be regulated by the PhoPQ system, this common regulator could explain curcumin's mode of action. This data urges us to rethink the indiscriminate use of curcumin especially during Salmonella outbreaks.

Experimental and Computational Characterization of Alloy--Spinel--Corundum Equilibrium in the System Fe--Co--Al--O at 1873K

The three-phase equilibrium between alloy, spinel solid solution and alpha -Al sub 2 O sub 3 in the Fe--Co--Al--O system at 1873k was fully characterized as a function of alloy composition using both experimental and computational methods. The equilibrium oxygen content of the liquid alloy was measured by suction sampling and inert gas fusion analysis. The O potential corresponding to the three-phase equilibrium was determined by emf measurements on a solid state galvanic cell incorporating (Y sub 2 O sub 3 )ThO sub 2 as the solid electrolyte and Cr + Cr sub 2 O sub 3 as the reference electrode. The equilibrium composition of the spinel phase formed at the interface between the alloy and alumina crucible was measured by electron probe microanalysis (EPMA). The experimental results were compared with the values computed using a thermodynamic model. The model used values for standard Gibbs energies of formation of pure end-member spinels and Gibbs energies of solution of gaseous O in liquid Fe and cobalt available in the literature. The activity--composition relationship in the spinel solid solution was computed using a cation distribution model. The variation of the activity coefficient of O with alloy composition in the Fe--Co--O system was estimated using both the quasichemical model of Jacob and Alcock and Wagner's model along with the correlations of Chiang and Chang and Kuo and Chang. The computed results of spinel composition and O potential are in excellent agreement with the experimental data. Graphs. 29 ref.--AA

Isobaric electrical resistance along the critical line in nickel: An experimental test of universality

High-precision measurement of the electrical resistance of nickel along its critical line, a first attempt of this kind, as a function of pressure to 47.5 kbar is reported. Our analysis yields the values of the critical exponents α=α’=-0.115±0.005 and the amplitude ratios ‖A/A’‖=1.17±0.07 and ‖D/D’‖=1.2±0.1. These values are in close agreement with those predicted by renormalization-group (RG) theory. Moreover, this investigation provides an unambiguous experimental verification to one of the key consequences of RG theory that the critical exponents and amplitudes ratios are insensitive to pressure variation in nickel, a Heisenberg ferromagnet.

Deformation and failure of a film/substrate system subjected to spherical indentation: Part 1. Experimental validation of stresses and strains derived using Hankel transform technique in an elastic film/substrate system

Our concern here is to rationalize experimental observations of failure modes brought about by indentation of hard thin ceramic films deposited on metallic substrates. By undertaking this exercise, we would like to evolve an analytical framework that can be used for designs of coatings. In Part I of the paper we develop an algorithm and test it for a model system. Using this analytical framework we address the issue of failure of columnar TiN films in Part II [J. Mater. Res. 21, 783 (2006)] of the paper. In this part, we used a previously derived Hankel transform procedure to derive stress and strain in a birefringent polymer film glued to a strong substrate and subjected to spherical indentation. We measure surface radial strains using strain gauges and bulk film stresses using photo elastic technique (stress freezing). For a boundary condition based on Hertzian traction with no film interface constraint and assuming the substrate constraint to be a function of the imposed strain, the theory describes the stress distributions well. The variation in peak stresses also demonstrates the usefulness of depositing even a soft film to protect an underlying substrate.

Experimental approach for studying structural changes in axonal membrane upon nerve excitation

The Hodgkin and Huxley (HH) model of action potential has become a central paradigm of neuroscience. Despite its ability to predict action potentials with remarkable accuracy, it fails to explain several biophysical findings related to the initiation and propagation of the nerve impulse. The isentropic heat release and optical phenomena demonstrated by various experiments suggest that action potential is accompanied by a transient phase change in the axonal membrane. In this study a method was developed for preparing a giant axon from the crayfish abdominal cord for studying the molecular mechanisms of action potential simultaneously by electrophysiological and optical methods. Also an alternative setup using a single-cell culture of an Aplysia sensory neuron is presented. In addition to the description of the method, the preliminary results on the effect of phloretin, a dipole potential lowering compound, on the excitability of a crayfish giant axon are presented.

Diesel Engine Driven Stand-Alone Variable Speed Constant Frequency Slip Ring Induction Generator - Theory and Experimental Results

The operation of a stand-alone, as opposed to grid connected generation system, using a slip-ring induction machine as the electrical generator, is considered. In contrast to an alternator, a slip-ring induction machine can run at variable speed and still deliver constant frequency power to loads. This feature enables optimization of the system when the prime mover is inherently variable speed in nature eg. wind turbines, as well as diesel driven systems, where there is scope for economizing on fuel consumption. Experimental results from a system driven by a 44 bhp diesel engine are presented. Operation at subsynchronous as well as super-synchronous speeds is examined. The measurement facilitates the understanding of the system as well as its design.

Influence of crossed electric and quantizing magnetic fields on the Einstein relation in nonlinear optical, optoelectronic and related materials: Simplified theory, relative comparison and suggestion for experimental determination

An attempt is made to study the Einstein relation for the diffusivity-to-mobility ratio (DMR) under crossed fields' configuration in nonlinear optical materials on the basis of a newly formulated electron dispersion law by incorporating the crystal field in the Hamiltonian and including the anisotropies of the effective electron mass and the spin-orbit splitting constants within the framework of kp formalisms. The corresponding results for III-V, ternary and quaternary compounds form a special case of our generalized analysis. The DMR has also been investigated for II-VI and stressed materials on the basis of various appropriate dispersion relations. We have considered n-CdGeAs2, n-Hg1-xCdxTe, n-In1-xGaxAsyP1-y lattice matched to InP, p-CdS and stressed n-InSb materials as examples. The DMR also increases with increasing electric field and the natures of oscillations are totally band structure dependent with different numerical values. It has been observed that the DMR exhibits oscillatory dependences with inverse quantizing magnetic field and carrier degeneracy due to the Subhnikov-de Haas effect. An experimental method of determining the DMR for degenerate materials in the present case has been suggested. (C) 2010 Elsevier B.V. All rights reserved.

Experimental investigation of the dependence of barrier height on metal work function for metal---SiO2---p---Si (MIS) Schottky-barrier diodes in the presence of inversion

The dependence of barrier height on the metal work function of metal-SiO2-p-Si Schottky barrier diodes was investigated and nonlinearity was found. This is explained by the theoretical model proposed recently by Chattopadhyay and Daw. The values of interface trap density and fixed charge density of the insulating layer of the diodes were calculated using this model and found to be appreciably different from those estimated by the usual method.

Experimental Verification of the Lateral Periodicity of Axially Periodic Incoherent Fields Using the Lau Effect

General' objects, which are specially prepared to possess restricted spatial frequency spectra, have been used in the conventional Lau experiment to obtain experimental proof for the existence of lateral periodicity arising from axial periodicity, for a subclass of axially periodic wavefields in an incoherent situation.

Molecular mechanisms of hypertension-induced heart failure : Experimental studies with special emphasis on local renin-angiotensin system, cardiac metabolism and levosimendan

Hypertension is a major risk factor for stroke, ischaemic heart disease, and the development of heart failure. Hypertension-induced heart failure is usually preceded by the development of left ventricular hypertrophy (LVH), which represents an adaptive and compensatory response to the increased cardiac workload. Biomechanical stress and neurohumoral activation are the most important triggers of pathologic hypertrophy and the transition of cardiac hypertrophy to heart failure. Non-clinical and clinical studies have also revealed derangements of energy metabolism in hypertensive heart failure. The goal of this study was to investigate in experimental models the molecular mechanisms and signalling pathways involved in hypertension-induced heart failure with special emphasis on local renin-angiotensin-aldosterone system (RAAS), cardiac metabolism, and calcium sensitizers, a novel class of inotropic agents used currently in the treatment of acute decompensated heart failure. Two different animal models of hypertensive heart failure were used in the present study, i.e. hypertensive and salt-sensitive Dahl/Rapp rats on a high salt diet (a salt-sensitive model of hypertensive heart failure) and double transgenic rats (dTGR) harboring human renin and human angiotensinogen genes (a transgenic model of hypertensive heart failure with increased local RAAS activity). The influence of angiotensin II (Ang II) on cardiac substrate utilization and cardiac metabolomic profile was investigated by using gas chromatography coupled to time-of-flight mass spectrometry to detect 247 intermediary metabolites. It was found that Ang II could alter cardiac metabolomics both in normotensive and hypertensive rats in an Ang II receptor type 1 (AT1)-dependent manner. A distinct substrate use from fatty acid oxidation towards glycolysis was found in dTGR. Altered cardiac substrate utilization in dTGR was associated with mitochondrial dysfunction. Cardiac expression of the redox-sensitive metabolic sensor sirtuin1 (SIRT1) was increased in dTGR. Resveratrol supplementation prevented cardiovascular mortality and ameliorated Ang II-induced cardiac remodeling in dTGR via blood pressure-dependent pathways and mechanisms linked to increased mitochondrial biogenesis. Resveratrol dose-dependently increased SIRT1 activity in vitro. Oral levosimendan treatment was also found to improve survival and systolic function in dTGR via blood pressure-independent mechanisms, and ameliorate Ang II-induced coronary and cardiomyocyte damage. Finally, using Dahl/Rapp rats it was demonstrated that oral levosimendan as well as the AT1 receptor antagonist valsartan improved survival and prevented cardiac remodeling. The beneficial effects of levosimendan were associated with improved diastolic function without significantly improved systolic changes. These positive effects were potentiated when the drug combination was administered. In conclusion, the present study points to an important role for local RAAS in the pathophysiology of hypertension-induced heart failure as well as its involvement as a regulator of cardiac substrate utilization and mitochondrial function. Our findings suggest a therapeutic role for natural polyphenol resveratrol and calcium sensitizer, levosimendan, and the novel drug combination of valsartan and levosimendan, in prevention of hypertension-induced heart failure. The present study also provides a better understanding of the pathophysiology of hypertension-induced heart failure, and may help identify potential targets for novel therapeutic interventions.

Experimental estimation of friction force in lubricated cutting of steel

Friction force generated in lubricated cutting of steel is experimentally estimated by recording the tangential force experienced by the spherical face of a pin rubbing against a freshly cut surface. The pin and the cutting tool are both submerged in the lubricant and the pin is situated on the cut-track to record the force. The recording shows an instantaneous achievement of a peak in the force curve followed by a decline in time to a steady state value. The peak and not the steady state friction was found to be sensitive to the structure of the hydrocarbon and addition of additive to the oil. The configuration was designed and tested to demonstrate the influence of a reaction film which develops during cutting, on cutting tool friction. Given the strong correlation between the peak friction and the existence of a tribofilm in the cutting zone, the configuration is used to determine the lower limit of a cutting speed regime, which marks the initiation of lubricant starvation, in cutting of steel using an emulsion as a cutting fluid. (C) 2010 Elsevier B.V. All rights reserved.

Role of external electron donor in methylene blue sensitized dichromated gelatin holograms:an experimental study

An experimental study to ascertain the role of external electron donor in methylene blue sensitized dichromated gelatin (MBDCG) holograms has been carried out. The required volume holographic transmission gratings in MBDCG have been recorded using 633-nm light from a He-Ne laser. Three well-known electron donors, namely, N, N-dimethylformamide (DMF); ethylenediaminetetraacetic acid (EDTA); triethanolamine (TEA), were used in this study. The variation of diffraction efficiency (η) as a function of light exposure (E) and concentration (C) of the electron donor under consideration was chosen as the figure of merit for judging the role of external electron donor in MBDCG holograms. A self-consistent analysis of the experimental results was carried out by recalling the various known facts about the photochemistry and the hologram formation in DSDCG and also DCG. The important findings and conclusions are as follows: (i) Each η vs E graph is a bell-shaped curve and its peak height is influenced in a characteristic manner by the external electron donor used. (ii) High diffraction efficiency/recording speed can be achieved in pure MBDCG holograms. (iii) The diffraction efficiency/recording speed achieved in electron donor sensitized MBDCG holograms did not show any significant improvement at all over that observed in pure MBDCG holograms. (iv) In electron donor sensitized MBDCG holograms, the electron donor used, depending on its type and concentration, appears to promote the process of cross-linking of gelatin molecules in a manner to either retain or deteriorate the refractive-index modulation achieved using pure MBDCG.