Sonic hedgehog-Dependent Induction of MicroRNA 31 and MicroRNA 150 Regulates Mycobacterium bovis BCG-Driven Toll-Like Receptor 2 Signaling

Hedgehog (HH) signaling is a significant regulator of cell fate decisions during embryogenesis, development, and perpetuation of various disease conditions. Testing whether pathogen-specific HH signaling promotes unique innate recognition of intracellular bacteria, we demonstrate that among diverse Gram-positive or Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly, sustained tumor necrosis factor alpha (TNF-alpha) secretion by macrophages was essential for robust SHH activation, as TNF-alpha(-/-) macrophages exhibited compromised ability to activate SHH signaling. Neutralization of TNF-alpha or blockade of TNF-alpha receptor signaling significantly reduced the infection-induced SHH signaling activation both in vitro and in vivo. Intriguingly, activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2 (TLR2) signaling events to regulate a battery of genes associated with divergent functions of M1/M2 macrophages. Genome-wide expression profiling as well as conventional gain-of-function or loss-of-function analysis showed that SHH signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH signaling signatures could be detected in vivo in tuberculosis patients and M. bovis BCG-challenged mice. Collectively, these investigations identify SHH signaling to be what we believe is one of the significant regulators of host-pathogen interactions.

Support vector machine based high speed protection relay for EHV/UHV transmission line

This paper presents a fast and accurate relaying technique for a long 765kv UHV transmission line based on support vector machine. For a long EHV/UHV transmission line with large distributed capacitance, a traditional distance relay which uses a lumped parameter model of the transmission line can cause malfunction of the relay. With a frequency of 1kHz, 1/4th cycle of instantaneous values of currents and voltages of all phases at the relying end are fed to Support Vector Machine(SVM). The SVM detects fault type accurately using 3 milliseconds of post-fault data and reduces the fault clearing time which improves the system stability and power transfer capability. The performance of relaying scheme has been checked with a typical 765kV Indian transmission System which is simulated using the Electromagnetic Transients Program(EMTP) developed by authors in which the distributed parameter line model is used. More than 15,000 different short circuit fault cases are simulated by varying fault location, fault impedance, fault incidence angle and fault type to train the SVM for high speed accurate relaying. Simulation studies have shown that the proposed relay provides fast and accurate protection irrespective of fault location, fault impedance, incidence time of fault and fault type. And also the proposed scheme can be used as augmentation for the existing relaying, particularly for Zone-2, Zone-3 protection.

Effect of composition on thermoelectric properties of polycrystalline CrSi2

Ingots with compositions CrSi2-x (with 0 < x < 0.1) were synthesized by vacuum arc melting followed by uniaxial hot pressing for densification. This paper reports the temperature and composition dependence of the electrical resistivity, Seebeck coefficient, and thermal conductivity of CrSi2-x samples in the temperature range of 300 K to 800 K. The silicon-deficient samples exhibited substantial reductions in resistivity and Seebeck coefficient over the measured temperature range due to the formation of metallic secondary CrSi phase embedded in the CrSi2 matrix phase. The thermal conductivity was seen to exhibit a U-shaped curve with respect to x, exhibiting a minimum value at the composition of x = 0.04. However, the limit of the homogeneity range of CrSi2 suppresses any further decrease of the lattice thermal conductivity. As a consequence, the maximum figure of merit of ZT = 0.1 is obtained at 650 K for CrSi1.98.

Multilevel octadecagonal space vector generation for induction motor drives by cascading asymmetric three level inverters

Multilevel inverters with hexagonal and dodecagonal voltage space vector structures have improved harmonic profile compared to two level inverters. Further improvement in the quality of the waveform is possible using multilevel octadecagonal (18 sided polygon) voltage space vectors. This paper proposes an inverter circuit topology capable of generating multilevel octadecagonal voltage space vectors, by cascading two asymmetric three level inverters. By proper selection of DC link voltages and the resultant switching states for the inverters, voltage space vectors, whose tips lie on three concentric octadecagons, are obtained. The advantages of octadecagonal voltage space vector based PWM techniques are the complete elimination of fifth, seventh, eleventh and thirteenth harmonics in phase voltages and the extension of linear modulation range. In this paper, a simple PWM timing calculation method is also proposed. Matlab simulation results and experimental results have been presented in this paper to validate the proposed concept.

Antibody-mediated catalysis: Induction and therapeutic relevance

Abzymes are immunoglobulins endowed with enzymatic activities. The catalytic activity of an abzyme resides in the variable domain of the antibody, which is constituted by the close spatial arrangement of amino acid residues involved in catalysis. The origin of abzymes is conferred by the innate diversity of the immunoglobulin gene repertoire. Under deregulated immune conditions, as in autoimmune diseases, the generation of abzymes to self-antigens could be deleterious. Technical advancement in the ability to generate monoclonal antibodies has been exploited in the generation of abzymes with defined specificities and activities. Therapeutic applications of abzymes are being investigated with the generation of monoclonal abzymes against several pathogenesis-associated antigens. Here, we review the different contexts in which abzymes are generated, and we discuss the relevance of monoclonal abzymes for the treatment of human diseases.

Molecular flexibility tuned emission in ``V'' shaped naphthalimides: Hg(II) detection and aggregation-induced emission enhancement (AIEE)

Four ``V'' shaped 1,8-naphthalimides (1-4) have been synthesized and their fluorescence quantum-yields correlated to their molecular flexibility. The correlation was used for detection of Hg(II) via a chemodosimetric approach. 4 was found to be an AIE active molecule with the formation of fluorescent nanoaggregates.

Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance. Intravenous immunoglobulin (IVIg), a therapeutic preparation of normal pooled human IgG, expands Tregs in various experimental models and in patients. However, the cellular and molecular mechanisms by which IVIg expands Tregs are relatively unknown. As Treg expansion in the periphery requires signaling by antigen-presenting cells such as dendritic cells (DCs) and IVIg has been demonstrated to modulate DC functions, we hypothesized that IVIg induces distinct signaling events in DCs that subsequently mediate Treg expansion. We demonstrate that IVIg expands Tregs via induction of cyclooxygenase (COX)-2-dependent prostaglandin E2 (PGE(2)) in human DCs. However, costimulatory molecules of DCs such as programmed death ligands, OX40 ligand, and inducible T-cell costimulator ligands were not implicated. Inhibition of PGE(2) synthesis by COX-2 inhibitors prevented IVIg-mediated Treg expansion in vitro and significantly diminished IVIg-mediated Treg expansion in vivo and protection from disease in experimental autoimmune encephalomyelitis model. IVIg-mediated COX-2 expression, PGE(2) production, and Treg expansion were mediated in part via interaction of IVIg and F(ab('))(2) fragments of IVIg with DC-specific intercellular adhesion molecule-3-grabbing nonintegrin. Our results thus uncover novel cellular and molecular mechanism by which IVIg expands Tregs.

Role of electrolyte chemistry on electronic and in vitro electrochemical properties of micro-arc oxidized titania films on Cp Ti

The primary objective of the present work was to study the electronic and in vitro electrochemical properties of micro-arc oxidized titania films on Cp Ti, fabricated independently in various electrolyte solutions consisting of anions such as phosphate (PO43-), borate (B4O72-), citrate (C6H5O73-) and silicate (SiO32-). Further the role of anions on the structural, morphological and compositional properties of the fabricated films was studied. All the titania films were developed by micro-arc oxidation (MAO) technique for a fixed treatment time of 8 min under constant current mode. The surface morphology, elemental distribution, composition and structural characteristics of the films were assessed by scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD) techniques. The thermodynamic and kinetic corrosion properties of the films were studied under simulated body fluid (SBF) conditions (pH 7.4 and 37 degrees C) by conducting chronopotentiometric and potentiodynamic polarization tests. Electrochemical impedance spectroscopy (EIS) coupled with equivalent circuit modelling was carried out to analyse the frequency response and Mott-Schottky analysis was performed to study the semiconducting (electronic) properties of the films. Salt spray fog accelerated corrosion test was conducted for 168h as per ASTM B117 standard to corroborate the corrosion and semiconducting properties of the samples based on the visual examination. The XRD results showed that the transformation from the metastable anatase phase to the thermodynamically stable rutile phase and the crystalline growth of the respective phases were strongly influenced by the addition of anions. The SEM-EDS results demonstrated that the phosphorous (P) content in the films varied from 2.4 at% to 5.0 at% indicating that the amount of P in the films could be modified by adding an appropriate electrolyte additive. The electrochemical corrosion test results showed that the film fabricated in citrate (C6H5O73-) containing electrolyte is thermodynamically and kinetically more stable compared to that of all the others. The results of the Mott-Schottky analysis indicated that all the fabricated films showed an n-type semiconducting behaviour and the film developed in citrate (C6H5O73-) containing electrolyte exhibited the lowest donor concentration and the most negative flat band potential that contributed to its highest corrosion resistance in SBF solution. The results of the salt spray accelerated corrosion tests were in agreement with those obtained from the electrochemical and Mott-Schottky analysis.

Induction of Supramolecular Chirality in the Self-Assemblies of Lipophilic Pyrimidine Derivatives by Choice of the Amino Acid-Based Chiral Spacer

A new family of supramolecular organogelators, based on chiral amino acid derivatives of 2,4,6-trichloro-pyrimidine-5-carbaldehyde, has been synthesized. L-alanine was incorporated as a spacer between the pyrimidine core and long hydrocarbon tails to compare the effect of chirality and hydrogen bonding to that of the achiral analogue. The role of aromatic moiety on the chiral spacer was also investigated by introducing L-phenyl alanine moieties. The presence of intermolecular hydrogen-bonding leading to the chiral self-assembly was probed by concentration-dependent FTIR and UV/Vis spectroscopies, in addition to circular dichroism (CD) studies. Temperature and concentration-dependent CD spectroscopy ascribed to the formation of -sheet-type H-bonded networks. The morphology and the arrangements of the molecules in the freeze-dried gels were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray diffraction (XRD) techniques. Calculation of the length of each molecular system by energy minimization in its extended conformation and comparison with the small-angle XRD pattern reveals that this class of gelator molecules adopts a lamellar organization. Polarized optical microscopy (POM) and differential scanning calorimetry (DSC) indicate that the solid state phase behavior of these molecules is totally dependent on the choice of their amino acid spacers. Structure-induced aggregation properties based on the H-bonding motifs and the packing of the molecule in three dimensions leading to gelation was elucidated by rheological studies. However, viscoelasticity was shown to depend only marginally on the H-bonding interactions; rather it depends on the packing of the gelators to a greater extent.

A Medium-Voltage Inverter-Fed IM Drive Using Multilevel 12-Sided Polygonal Vectors, With Nearly Constant Switching Frequency Current Hysteresis Controller

In this paper, a current error space vector (CESV)-based hysteresis current controller for a multilevel 12-sided voltage space vector-based inverter-fed induction motor (IM) drive is proposed. The proposed controller gives a nearly constant switching frequency operation throughout different speeds in the linear modulation region. It achieves the elimination of 6n +/- 1, n = odd harmonics from the phase voltages and currents in the entire modulation range, with an increase in the linear modulation range. It also exhibits fast dynamic behavior under different transient conditions and has a simple controller implementation. Nearly constant switching frequency is obtained by matching the steady-state CESV boundaries of the proposed controller with that of a constant switching frequency SVPWM-based drive. In the proposed controller, the CESV reference boundaries are computed online, using the switching dwell time and voltage error vector of each applied vector. These quantities are calculated from estimated sampled reference phase voltages. Vector change is decided by projecting the actual current error along the computed hysteresis space vector boundary of the presently applied vector. The estimated reference phase voltages are found from the stator current error ripple and the parameters of the IM.

Support vector clustering-based direct coherency identification of generators in a multi-machine power system

This study investigates the application of support vector clustering (SVC) for the direct identification of coherent synchronous generators in large interconnected multi-machine power systems. The clustering is based on coherency measure, which indicates the degree of coherency between any pair of generators. The proposed SVC algorithm processes the coherency measure matrix that is formulated using the generator rotor measurements to cluster the coherent generators. The proposed approach is demonstrated on IEEE 10 generator 39-bus system and an equivalent 35 generators, 246-bus system of practical Indian southern grid. The effect of number of data samples and fault locations are also examined for determining the accuracy of the proposed approach. An extended comparison with other clustering techniques is also included, to show the effectiveness of the proposed approach in grouping the data into coherent groups of generators. This effectiveness of the coherent clusters obtained with the proposed approach is compared in terms of a set of clustering validity indicators and in terms of statistical assessment that is based on the coherency degree of a generator pair.

A Quick-Simulation Tool for Induction Motor Drives Controlled Using Advanced Space-Vector-Based PWM Techniques

Space-vector-based pulse width modulation (PWM) for a voltage source inverter (VSI) offers flexibility in terms of different switching sequences. Numerical simulation is helpful to assess the performance of a PWM method before actual implementation. A quick-simulation tool to simulate a variety of space-vector-based PWM strategies for a two-level VSI-fed squirrel cage induction motor drive is presented. The simulator is developed using C and Python programming languages, and has a graphical user interface (GUI) also. The prime focus being PWM strategies, the simulator developed is 40 times faster than MATLAB in terms of the actual time taken for a simulation. Simulation and experimental results are presented on a 5-hp ac motor drive.

A Committee Machine Approach for Compressed Sensing Signal Reconstruction

Although many sparse recovery algorithms have been proposed recently in compressed sensing (CS), it is well known that the performance of any sparse recovery algorithm depends on many parameters like dimension of the sparse signal, level of sparsity, and measurement noise power. It has been observed that a satisfactory performance of the sparse recovery algorithms requires a minimum number of measurements. This minimum number is different for different algorithms. In many applications, the number of measurements is unlikely to meet this requirement and any scheme to improve performance with fewer measurements is of significant interest in CS. Empirically, it has also been observed that the performance of the sparse recovery algorithms also depends on the underlying statistical distribution of the nonzero elements of the signal, which may not be known a priori in practice. Interestingly, it can be observed that the performance degradation of the sparse recovery algorithms in these cases does not always imply a complete failure. In this paper, we study this scenario and show that by fusing the estimates of multiple sparse recovery algorithms, which work with different principles, we can improve the sparse signal recovery. We present the theoretical analysis to derive sufficient conditions for performance improvement of the proposed schemes. We demonstrate the advantage of the proposed methods through numerical simulations for both synthetic and real signals.

Neoarchean continental growth through arc magmatism in the Nilgiri Block, southern India

The formation and growth of continental crust in the Archean have been evaluated through models of subduction-accretion and mantle plume. The Nilgiri Block in southern India exposes exhumed Neoarchean lower crust, uplifted to heights of 2500 m above sea level along the north western margin of the Peninsula. Major lithologies in this block include charnockite with or without garnet, anorthosite-gabbro suite, pyroxenite, amphibolite and hornblende-biotite gneiss (TTG). All these rock types are closely associated as an arc magmatic suite, with diffuse boundaries and coeval nature. The charnockite and hornblende-biotite gneisses (TTG) show SiO2 content varying from 64 to 73 wt.%. The hornblende-biotite gneisses (TTG) are high-Al type with Al2O3 >15 wt.% whereas the charnockites show Al2O3 <15 wt.%. The composition of charnockite is mainly magnesian and calcic to calc-alkaline. The mafic-ultramafic rocks show composition close to that of tholeiitic series. The low values of K(2)o (<3 wt.%), (K/Rb)/K2O (<500), Zr/Ti, and trace element ratios like (La/Yb)n/(Sr/Y), (Y/Nb), (Y + Nb)/Rb, (Y+Ta)/Rb, Yb/Ta indicate a volcanic arc signature for these rocks. The geochemical signature is consistent with arc magmatic rocks generated through oceanic plate subduction. The primitive mantle normalized trace element patterns of these rocks display enrichment in large ion lithophile elements (LILE) and comparable high field strength elements (HFSE) in charnockite and hornblende-biotite gneisses (TTG) consistent with subduction-related origin. Primitive mantle normalized REE pattern displays an enrichment in LREE in the chamockite and hornblende-biotite gneisses (TTG) as compared to a flat pattern for the mafic rocks. The chondrite normalized REE patterns of zircons of all the rock types reveal cores with high HREE formed at ca. 2700 Ma and rims with low HREE formed at 2500-2450 Ma. Log-transformed La/Th-Nb/Th-Sm/Th-Yb/Th discrimination diagram for the mafic and ultramafic rocks from Nilgiri displays a transition from mid-oceanic ridge basalt (MORB) to island arc basalt (IAB) suggesting a MORB source. The U-Pb zircon data from the charnockites, mafic granulites and hornblende-biotite gneisses (TTG) presented in our study show that the magma generation during subduction and accretion events in this block occurred at 2700-2500 Ma. Together with the recent report on Neoarchean supra-subduction zone ophiolite suite at its southern margin, the Nilgiri Block provides one of the best examples for continental growth through vertical stacking and lateral accretion in a subduction environment during the Neoarchean. (c) 2014 Elsevier B.V. All rights reserved.

A Harmonic Suppression Scheme for Open-End Winding Split-Phase IM Drive Using Capacitive Filters for the Full Speed Range

Voltage source inverter (VSI)-fed six-phase induction motor (IM) drives have high 6n +/- 1, n = odd-order harmonic currents. This is because these currents, driven by the corresponding harmonic voltages in the inverter output, are limited only by the stator leakage impedance, as these harmonics are absent in the back electromotive force of the motor. To suppress the harmonic currents, either bulky inductive harmonic filters or complex pulsewidth modulation (PWM) techniques have to be used. This paper proposes a harmonic elimination scheme using switched capacitor filters for a VSI-fed split-phase IM drive. Two 3-phase inverters fed from capacitors are used on the open-end side of the motor to suppress 6n +/- 1, n = odd-order harmonics. A PWM scheme that can suppress the harmonics as well as balance the capacitor voltage is also proposed. The capacitor fed inverters are switched so that the fundamental voltage is not affected, and the fundamental power is always drawn from the main inverters. The proposed scheme is verified with a detailed experimental study. The effectiveness of the scheme is demonstrated by comparing the results with those obtained by disabling the capacitor fed inverters.