Nitric oxide and KLF4 protein epigenetically modify class II transactivator to repress Major histocompatibility complex II expression during Mycobacterium bovis Bacillus Calmette-Guerin infection

Pathogenic mycobacteria employ several immune evasion strategies such as inhibition of class II transactivator (CIITA) and MHC-II expression, to survive and persist in host macrophages. However, precise roles for specific signaling components executing down-regulation of CIITA/MHC-II have not been adequately addressed. Here, we demonstrate that Mycobacterium bovis bacillus Calmette-Guerin (BCG)-mediated TLR2 signaling-induced iNOS/NO expression is obligatory for the suppression of IFN-gamma-induced CIITA/MHC-II functions. Significantly, NOTCH/PKC/MAPK-triggered signaling cross-talk was found critical for iNOS/NO production. NO responsive recruitment of a bifunctional transcription factor, KLF4, to the promoter of CIITA during M. bovis BCG infection of macrophages was essential to orchestrate the epigenetic modifications mediated by histone methyltransferase EZH2 or miR-150 and thus calibrate CIITA/MHC-II expression. NO-dependent KLF4 regulated the processing and presentation of ovalbumin by infected macrophages to reactive T cells. Altogether, our study delineates a novel role for iNOS/NO/KLF4 in dictating the mycobacterial capacity to inhibit CIITA/MHC-II-mediated antigen presentation by infected macrophages and thereby elude immune surveillance.

Transition in subicular burst firing neurons from epileptiform activity to suppressed state by feedforward inhibition

The subiculum, a para-hippocampal structure positioned between the cornu ammonis 1 subfield and the entorhinal cortex, has been implicated in temporal lobe epilepsy in human patients and in animal models of epilepsy. The structure is characterized by the presence of a significant population of burst firing neurons that has been shown previously to lead epileptiform activity locally. Phase transitions in epileptiform activity in neurons following a prolonged challenge with an epileptogenic stimulus has been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of phase transitions in the burst firing neurons of the subiculum in an in vitro rat brain slice model of epileptogenesis. Whole-cell patch-clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable state was followed by a late suppressed state upon continuous perfusion with epileptogenic 4-aminopyridine and magnesium-free medium. The suppressed state was characterized by inhibitory post-synaptic potentials in pyramidal excitatory neurons and bursting activity in local fast-spiking interneurons at a frequency of 0.1-0.8Hz. The inhibitory post-synaptic potentials were mediated by GABA(A) receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These inhibitory post-synaptic potentials ceased following a cut between the cornu ammonis 1 and subiculum. The suppression of epileptiform activity in the subiculum thus represents a homeostatic response towards the induced hyperexcitability. Our results suggest the importance of feedforward inhibition in exerting this homeostatic control.

Is chemically synthesized Graphene `really' a unique substrate for SERS and fluorescence quenching?

We demonstrate observation of Raman signals of different analytes adsorbed on carbonaceous materials, such as, chemically reduced graphene, graphene oxide (GO), multi-walled carbon nanotube (MWCNT), graphite and activated carbon. The analytes selected for the study were Rhodamine 6G (R6G) (in resonant conditions), Rhodamine B (RB), Nile blue (NBA), Crystal Violet (CV) and acetaminophen (paracetamol). All the analytes except paracetamol absorb and fluoresce in the visible region. In this article we provide experimental evidence of the fact that observation of Raman signals of analytes on such carbonaceous materials are more due to resonance effect, suppression of fluorescence and efficient adsorption and that this property in not unique to graphene or nanotubes but prevalent for various type of carbon materials.

NOD2-Nitric Oxide-responsive MicroRNA-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease

Background: Genetic variants of NOD2 are linked to inflammatory bowel disease (IBD) etiology. Results: DSS model of colitis in wild-type and inducible nitric-oxide synthase (iNOS) null mice revealed that NOD2-iNOS/NO-responsive microRNA-146a targets NUMB gene facilitating Sonic hedgehog (SHH) signaling. Conclusion: miR-146a-mediated NOD2-SHH signaling regulates gut inflammation. Significance: Identification of novel regulators of IBD provides new insights into pathophysiology and development of new therapy concepts. Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disorder of the intestine. The interactions between enteric bacteria and genetic susceptibilities are major contributors of IBD etiology. Although genetic variants with loss or gain of NOD2 functions have been linked to IBD susceptibility, the mechanisms coordinating NOD2 downstream signaling, especially in macrophages, during IBD pathogenesis are not precisely identified. Here, studies utilizing the murine dextran sodium sulfate model of colitis revealed the crucial roles for inducible nitric-oxide synthase (iNOS) in regulating pathophysiology of IBDs. Importantly, stimulation of NOD2 failed to activate Sonic hedgehog (SHH) signaling in iNOS null macrophages, implicating NO mediated cross-talk between NOD2 and SHH signaling. NOD2 signaling up-regulated the expression of a NO-responsive microRNA, miR-146a, that targeted NUMB gene and alleviated the suppression of SHH signaling. In vivo and ex vivo studies confirmed the important roles for miR-146a in amplifying inflammatory responses. Collectively, we have identified new roles for miR-146a that established novel cross-talk between NOD2-SHH signaling during gut inflammation. Potential implications of these observations in therapeutics could increase the possibility of defining and developing better regimes to treat IBD pathophysiology.

Chemical vapor detection using nonlinear electrical properties of carbon nanotube bundles

We demonstrate the electrical transport behavior of carbon nanotubes (CNTs) upon exposure to organic analytes (namely ethanol, benzene, acetone and toluene). The resulting nonlinear current-voltage characteristics revealed a power law dependence of the differential conductivity on the applied bias voltage. Moreover, suppression of differential conductivity at zero bias is found to be dependent on different selective analytes. The power law exponent values have been monitored before, during and after exposure to the chemicals, which revealed a reversible change in the number of electron conducting channels. Therefore, the reduction in the number of conductive paths can be attributed to the interaction of the chemical analyte on the CNT surfaces, which causes a decrease in the differential conductivity of the CNT sample. These results demonstrate chemical selectivity of CNTs due to varying electronic interaction with different chemical analytes.

Metal nanoparticles as better protein-aggregation prevention agents than chaperones

Prevention or suppression of protein aggregation is of great importance in the context of protein storage, transportation and delivery. Traditionally chaperones or other chemically active agents are used to stop or diffuse native protein aggregation. We have used gold nanoparticles to prevent thermal aggregation of alcohol dehydrogenase (ADH), a protein that maintains the alcohol level in the liver and stomach. A light-scattering assay has been used to investigate the effect of gold nanoparticles on thermal aggregation of ADH and the result of our study has been summarized in Fig. 1. The scattered light intensity from the solution containing ADH decreases when 45 nm gold nanoparticles are added prior to heating (thermal denaturation) the solution, which indicates prevention of aggregation. The aggregation of the protein is suppressed to the extent of 96% with picomolar concentration of 45 nm gold nanoparticles while micromolar amounts of other proteins and biological substances are necessary to achieve the same effect. The extent varies with the size and the concentration of the gold NPs for the same protein concentration.

BILATERAL EDGE DETECTORS

We propose to employ bilateral filters to solve the problem of edge detection. The proposed methodology presents an efficient and noise robust method for detecting edges. Classical bilateral filters smooth images without distorting edges. In this paper, we modify the bilateral filter to perform edge detection, which is the opposite of bilateral smoothing. The Gaussian domain kernel of the bilateral filter is replaced with an edge detection mask, and Gaussian range kernel is replaced with an inverted Gaussian kernel. The modified range kernel serves to emphasize dissimilar regions. The resulting approach effectively adapts the detection mask according as the pixel intensity differences. The results of the proposed algorithm are compared with those of standard edge detection masks. Comparisons of the bilateral edge detector with Canny edge detection algorithm, both after non-maximal suppression, are also provided. The results of our technique are observed to be better and noise-robust than those offered by methods employing masks alone, and are also comparable to the results from Canny edge detector, outperforming it in certain cases.

Tuning of the electro-mechanical behavior of the cellular carbon nanotube structures with nanoparticle dispersions

The mechanical and electrical characteristics of cellular network of the carbon nanotubes (CNT) impregnated with metallic and nonmetallic nanoparticles were examined simultaneously by employing the nanoindentation technique. Experimental results show that the nanoparticle dispersion not only enhances the mechanical strength of the cellular CNT by two orders of magnitude but also imparts variable nonlinear electrical characteristics; the latter depends on the contact resistance between nanoparticles and CNT, which is shown to depend on the applied load while indentation. Impregnation with silver nanoparticles enhances the electrical conductance, the dispersion with copper oxide and zinc oxide nanoparticles reduces the conductance of CNT network. In all cases, a power law behavior with suppression in the differential conductivity at zero bias was noted, indicating electron tunneling through the channels formed at the CNT-nanoparticle interfaces. These results open avenues for designing cellular CNT foams with desired electro-mechanical properties and coupling. (C) 2014 AIP Publishing LLC.

Enhancing the high temperature plasticity of a Cu-containing austenitic stainless steel through grain boundary strengthening

The addition of 3 wt% Cu to heat-resistant SUS 304H austenitic steel enhances its high temperature mechanical properties. To further improve the properties, particularly the creep resistance and ductility at high temperatures, a post-solutionizing heat-treatment method that involves an intermediated annealing either at 700 or 800 degrees C after solutionizing for durations up to 180 min was employed. The purpose this heat-treatment is to precipitate planar Cr23C6 at the grain boundaries, which results in the boundaries getting serrated. Detailed microstructural analyses of these `grain boundary engineered' alloys was conducted and their mechanical performance, both at room temperature and at 750 degrees C, was evaluated. While the grain size and texture are unaffected due to the high temperature hold, the volume fraction of Sigma 3 twin boundaries was found to increase significantly. While the strength enhancement was only marginal, the ductility was found to increase significantly, especially at high temperature. A marked increase in the creep resistance was also noted, which is attributed to the reduction of the grain boundary sliding by the grain boundary serrations and the suppression of grain boundary cavitation through the optimization of the volume fraction and spacing of the Cr23C6 precipitates. The special heat-treatment performed with holding time of 3 h at 700 degrees C resulted in the optimum combination of strength, ductility and creep resistance at high temperature. (C) 2014 Elsevier B.V. All rights reserved.

Characterising weather patterns associated with fire in a seasonally dry tropical forest in southern India

Anthropogenic fires in seasonally dry tropical forests are a regular occurrence during the dry season. Forest managers in India, who presently follow a fire suppression policy in such forests, would benefit from a system of assessing the potential risk to fire on a particular day. We examined the relationship between weather variables (seasonal rainfall, relative humidity, temperature) and days of fire during the dry seasons of 2004-2010, based on MODIS fire incident data in the seasonally dry tropical forests of Mudumalai in the Western Ghats, southern India. Logistic regression analysis showed that high probabilities of a fire day, indicating successful ignition of litter and grass fuel on the forest floor, were associated with low levels of early dry season rainfall, low daily average relative humidity and high daily average temperatures. These weather conditions are representative of low moisture levels of fine fuels, suggesting that the occurrence of fire is moderated by environmental conditions that reduce the flammability of fine fuels in the dry tropics. We propose a quantitative framework for assessing risk of a fire day to assist forest managers in anticipating fire occurrences in this seasonally dry tropical forest, and possibly for those across South Asia.

Multimodal shape oscillations of droplets excited by an air stream

The shape dynamics of droplets exposed to an air jet at intermediate droplet Reynolds numbers is investigated. High speed imaging and hot-wire anemometry are employed to examine the mechanism of droplet oscillation. The theory that the vortex shedding behind the droplet induces oscillation is examined. In these experiments, no particular dominant frequency is found in the wake region of the droplet. Hence the inherent free-stream disturbances prove to be driving the droplet oscillations. The modes of droplet oscillation show a band of dominant frequencies near the corresponding natural frequency, further proving that there is no particular forcing frequency involved. In the frequency spectrum of the lowest mode of oscillation for glycerol at the highest Reynolds number, no response is observed below the threshold frequency corresponding to the viscous dissipation time scale. This selective suppression of lower frequencies in the case of glycerol is corroborated by scaling arguments. The influence of surface tension on the droplet oscillation is studied using ethanol as a test fluid. Since a lower surface tension reduces the natural frequency, ethanol shows lower excited frequencies. The oscillation levels of different fluids are quantified using the droplet aspect ratio and correlated in terms of Weber number and Ohnesorge number. (C) 2014 Elsevier Ltd. All rights reserved.

Ductility enhancement in nanoglass: role of interaction stress between flow defects

Using a thermodynamically consistent non-local plasticity model, the mechanistic origin of enhancement in ductility and suppression of dominant shear banding in nanoglasses (NGs) is analysed. It is revealed that the interaction stress between flow defects plays a central role in promoting global plasticity of NGs. Specifically, we find that the intrinsic length associated with this stress provides a scaling for the shear band width and its coupling with grain size governs the level of enhancement in the deformation behaviour of NGs. The present work may provide useful insights in developing highly ductile NGs for practical engineering applications.

Spiral-wave dynamics in ionically realistic mathematical models for human ventricular tissue: the effects of periodic deformation

We carry out an extensive numerical study of the dynamics of spiral waves of electrical activation, in the presence of periodic deformation (PD) in two-dimensional simulation domains, in the biophysically realistic mathematical models of human ventricular tissue due to (a) ten-Tusscher and Panfilov (the TP06 model) and (b) ten-Tusscher, Noble, Noble, and Panfilov (the TNNPO4 model). We first consider simulations in cable-type domains, in which we calculate the conduction velocity theta and the wavelength lambda of a plane wave; we show that PD leads to a periodic, spatial modulation of theta and a temporally periodic modulation of lambda; both these modulations depend on the amplitude and frequency of the PD. We then examine three types of initial conditions for both TP06 and TNNPO4 models and show that the imposition of PD leads to a rich variety of spatiotemporal patterns in the transmembrane potential including states with a single rotating spiral (RS) wave, a spiral-turbulence (ST) state with a single meandering spiral, an ST state with multiple broken spirals, and a state SA in which all spirals are absorbed at the boundaries of our simulation domain. We find, for both TP06 and TNNPO4 models, that spiral-wave dynamics depends sensitively on the amplitude and frequency of PD and the initial condition. We examine how these different types of spiral-wave states can be eliminated in the presence of PD by the application of low-amplitude pulses by square- and rectangular-mesh suppression techniques. We suggest specific experiments that can test the results of our simulations.

On the Two-Step Mechanism for Synthesis of Transition-Metal Nanoparticles

The two-step particle synthesis mechanism, also known as the Finke-Watzky (1997) mechanism, has emerged as a significant development in the field of nanoparticle synthesis. It explains a characteristic feature of the synthesis of transition metal nanoparticles, an induction period in precursor concentration followed by its rapid sigmoidal decrease. The classical LaMer theory (1950) of particle formation fails to capture this behavior. The two-step mechanism considers slow continuous nucleation and autocatalytic growth of particles directly from precursor as its two kinetic steps. In the present work, we test the two-step mechanism rigorously using population balance models. We find that it explains precursor consumption very well, but fails to explain particle synthesis. The effect of continued nucleation on particle synthesis is not suppressed sufficiently by the rapid autocatalytic growth of particles. The nucleation continues to increase breadth of size distributions to unexpectedly large values as compared to those observed experimentally. A number of variations of the original mechanism with additional reaction steps are investigated next. The simulations show that continued nucleation from the beginning of the synthesis leads to formation of highly polydisperse particles in all of the tested cases. A short nucleation window, realized with delayed onset of nucleation and its suppression soon after in one of the variations, appears as one way to explain all of the known experimental observations. The present investigations clearly establish the need to revisit the two-step particle synthesis mechanism.

Cross-correlation-aided transport in stochastically driven accretion flows

The origin of linear instability resulting in rotating sheared accretion flows has remained a controversial subject for a long time. While some explanations of such non-normal transient growth of disturbances in the Rayleigh stable limit were available for magnetized accretion flows, similar instabilities in the absence of magnetic perturbations remained unexplained. This dichotomy was resolved in two recent publications by Chattopadhyay and co-workers Mukhopadhyay and Chattopadhyay, J. Phys. A 46, 035501 (2013); Nath et al., Phys. Rev. E 88, 013010 (2013)] where it was shown that such instabilities, especially for nonmagnetized accretion flows, were introduced through interaction of the inherent stochastic noise in the system (even a ``cold'' accretion flow at 3000Kis too ``hot'' in the statistical parlance and is capable of inducing strong thermal modes) with the underlying Taylor-Couette flow profiles. Both studies, however, excluded the additional energy influx (or efflux) that could result from nonzero cross correlation of a noise perturbing the velocity flow, say, with the noise that is driving the vorticity flow (or equivalently the magnetic field and magnetic vorticity flow dynamics). Through the introduction of such a time symmetry violating effect, in this article we show that nonzero noise cross correlations essentially renormalize the strength of temporal correlations. Apart from an overall boost in the energy rate (both for spatial and temporal correlations, and hence in the ensemble averaged energy spectra), this results in mutual competition in growth rates of affected variables often resulting in suppression of oscillating Alfven waves at small times while leading to faster saturations at relatively longer time scales. The effects are seen to be more pronounced with magnetic field fluxes where the noise cross correlation magnifies the strength of the field concerned. Another remarkable feature noted specifically for the autocorrelation functions is the removal of energy degeneracy in the temporal profiles of fast growing non-normal modes leading to faster saturation with minimum oscillations. These results, including those presented in the previous two publications, now convincingly explain subcritical transition to turbulence in the linear limit for all possible situations that could now serve as the benchmark for nonlinear stability studies in Keplerian accretion disks.