Acoustic response of vortex breakdown modes in a coaxial isothermal unconfined swirling jet

The present experimental work is concerned with the study of amplitude dependent acoustic response of an isothermal coaxial swirling jet. The excitation amplitude is increased in five distinct steps at the burner's Helmholtz resonator mode (i.e., 100 Hz). Two flow states are compared, namely, sub-critical and super-critical vortex breakdown (VB) that occur before and after the critical conical sheet breakdown, respectively. The geometric swirl number is varied in the range 2.14-4.03. Under the influence of external pulsing, global response characteristics are studied based on the topological changes observed in time-averaged 2D flow field. These are obtained from high resolution 2D PIV (particle image velocimetry) in the longitudinal-mid plane. PIV results also illustrate the changes in the normalized vortex core coordinates (r(vcc)/(r(vcc))(0) (Hz), y(vcc)/(y(vcc))(0) (Hz)) of internal recirculation zone (IRZ). A strong forced response is observed at 100 Hz (excitation frequency) in the convectively unstable region which get amplified based on the magnitude of external forcing. The radial extent of this forced response region at a given excitation amplitude is represented by the acoustic response region (b). The topological placement of the responsive convectively unstable region is a function of both the intensity of imparted swirl (characterized by swirl number) and forcing amplitude. It is observed that for sub-critical VB mode, an increase in the excitation amplitude till a critical value shifts the vortex core centre (particularly, the vortex core moves downstream and radially outwards) leading to drastic fanning-out/widening of the IRZ. This is accompanied by similar to 30% reduction in the recirculation velocity of the IRZ. It is also observed that b < R (R: radial distance from central axis to outer shear layer-OSL). At super-critical amplitudes, the sub-critical IRZ topology transits back (the vortex core retracts upstream and radially inwards) and finally undergoes a transverse shrinkage ((r(vcc))/(r(vcc))(0 Hz) decreases by similar to 20%) when b >= R. In contrast, the vortex core of super-critical breakdown mode consistently spreads radially outwards and is displaced further downstream. Finally, the IRZ fans-out at the threshold excitation amplitude. However, the acoustic response region b is still less than R. This is explained based on the characteristic geometric swirl number (S-G) of the flow regimes. The super-critical flow mode with higher S-G (hence, higher radial pressure drop due to rotational effect which scales as Delta P similar to rho u theta(2) and acts inwards towards the center line) compared to sub-critical state imposes a greater resistance to the radial outward spread of b. As a result, the acoustic energy supplied to the super-critical flow mode increases the degree of acoustic response at the pulsing frequency and energizes its harmonics (evident from power spectra). As a disturbance amplifier, the stronger convective instability mode within the flow structure of super-critical VB causes the topology to widen/fan-out severely at threshold excitation amplitude. (C) 2015 AIP Publishing LLC.

Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from Cicer arietinum

Calcium plays a crucial role as a secondary messenger in all aspects of plant growth, development and survival. Calcium dependent protein kinases (CDPKs) are the major calcium decoders, which couple the changes in calcium level to an appropriate physiological response. The mechanism by which calcium regulates CDPK protein is not well understood. In this study, we investigated the interactions of Ca2+ ions with the CDPK1 isoform of Cicer arietinum (CaCDPK1) using a combination of biophysical tools. CaCDPK1 has four different EF hands as predicted by protein sequence analysis. The fluorescence emission spectrum of CaCDPK1 showed quenching with a 5 nm red shift upon addition of calcium, indicating conformational changes in the tertiary structure. The plot of changes in intensity against calcium concentrations showed a biphasic curve with binding constants of 1.29 mu M and 120 mu M indicating two kinds of binding sites. Isothermal calorimetric (ITC) titration with CaCl2 also showed a biphasic curve with two binding constants of 0.027 mu M and 1.7 mu M. Circular dichroism (CD) spectra showed two prominent peaks at 208 and 222 nm indicating that CaCDPK1 is a alpha-helical rich protein. Calcium binding further increased the alpha-helical content of CaCDPK1 from 75 to 81%. Addition of calcium to CaCDPK1 also increased fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS) indicating exposure of hydrophobic surfaces. Thus, on the whole this study provides evidence for calcium induced conformational changes, exposure of hydrophobic surfaces and heterogeneity of EF hands in CaCDPK1. (C) 2015 Elsevier GmbH. All rights reserved.

Theoretical Insights to Niobium-Doped Monolayer MoS2-Gold Contact

We report a first principles study of the electronic properties for a contact formed between Nb-doped monolayer MoS2 and gold for different doping concentrations. We first focus on the shift of energy levels in band structure and the density of states with respect to the Fermi level for a geometrically optimized 5 x 5 MoS2 supercell for both pristine and Nb-doped structures. The doping is achieved by substituting Mo atoms with Nb atoms at random positions. It is observed that for an experimentally reported sheet hole doping concentration of (rho(2D)) 1.8 x 10(14) cm(-2), the pristine MoS2 converts to degenerate p-type semiconductor. Next, we interface this supercell with six layers of < 111 > cleaved surface of gold to investigate the contact nature of MoS2-Au system. By careful examination of projected band structure, projected density of states, effective potential and charge density difference, we demonstrate that the Schottky barrier nature observed for pure MoS2-Au contact can be converted from n-type to p-type by efficient Nb doping.

Interaction of a vortex ring with a single bubble: bubble and vorticity dynamics

The interaction of a single bubble with a single vortex ring in water has been studied experimentally. Measurements of both the bubble dynamics and vorticity dynamics have been done to help understand the two-way coupled problem. The circulation strength of the vortex ring (Gamma) has been systematically varied, while keeping the bubble diameter (D-b) constant, with the bubble volume to vortex core volume ratio (V-R) also kept fixed at about 0.1. The other important parameter in the problem is a Weber number based on the vortex ring strength. (We = 0.87 rho(Gamma/2 pi a)(2)/(sigma/D-b); a = vortex core radius, sigma = surface tension), which is varied over a large range, We = 3-406. The interaction between the bubble and ring for each of the We cases broadly falls into four stages. Stage I is before capture of the bubble by the ring where the bubble is drawn into the low-pressure vortex core, while in stage II the bubble is stretched in the azimuthal direction within the ring and gradually broken up into a number of smaller bubbles. Following this, in stage III the bubble break-up is complete and the resulting smaller bubbles slowly move around the core, and finally in stage IV the bubbles escape. Apart from the effect of the ring on the bubble, the bubble is also shown to significantly affect the vortex ring, especially at low We (We similar to 3). In these low-We cases, the convection speed drops significantly compared to the base case without a bubble, while the core appears to fragment with a resultant large decrease in enstrophy by about 50 %. In the higher-We cases (We > 100), there are some differences in convection speed and enstrophy, but the effects are relatively small. The most dramatic effects of the bubble on the ring are found for thicker core rings at low We (We similar to 3) with the vortex ring almost stopping after interacting with the bubble, and the core fragmenting into two parts. The present idealized experiments exhibit many phenomena also seen in bubbly turbulent flows such as reduction in enstrophy, suppression of structures, enhancement of energy at small scales and reduction in energy at large scales. These similarities suggest that results from the present experiments can be helpful in better understanding interactions of bubbles with eddies in turbulent flows.

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library(TM) using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously. With the help of the target-based approach we have found very potent hits inhibiting the selected target enzymes, but good minimal inhibitory concentrations (MIC) against M. tuberculosis were not achieved. Focussing on the whole cell-based approach several potent hits were found which displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10 mu M and were non-mutagenic, non-cytotoxic and the targets of some of the hits were also identified. The most active hits represented various scaffolds. Medicinal chemistry-based lead optimization was performed applying various strategies and, as a consequence, a series of novel potent compounds were synthesized. These efforts resulted in some effective potential antitubercular lead compounds which were confirmed in phenotypic assays. (C) 2015 Elsevier Ltd. All rights reserved.

Bioengineering of AAV2 Capsid at Specific Serine, Threonine, or Lysine Residues Improves Its Transduction Efficiency in Vitro and in Vivo

We hypothesized that the AAV2 vector is targeted for destruction in the cytoplasm by the host cellular kinase/ubiquitination/proteasomal machinery and that modification of their targets on AAV2 capsid may improve its transduction efficiency. In vitro analysis with pharmacological inhibitors of cellular serine/threonine kinases (protein kinase A, protein kinase C, casein kinase II) showed an increase (20-90%) on AAV2-mediated gene expression. The three-dimensional structure of AAV2 capsid was then analyzed to predict the sites of ubiquitination and phosphorylation. Three phosphodegrons, which are the phosphorylation sites recognized as degradation signals by ubiquitin ligases, were identified. Mutation targets comprising eight serine (S) or seven threonine (T) or nine lysine (K) residues were selected in and around phosphodegrons on the basis of their solvent accessibility, overlap with the receptor binding regions, overlap with interaction interfaces of capsid proteins, and their evolutionary conservation across AAV serotypes. AAV2-EGFP vectors with the wild-type (WT) capsid or mutant capsids (15 S/T -> alanine A] or 9 K -> arginine R] single mutant or 2 double K -> R mutants) were then evaluated in vitro. The transduction efficiencies of 11 S/T -> A and 7 K -> R vectors were significantly higher (similar to 63-90%) than the AAV2-WT vectors (similar to 30-40%). Further, hepatic gene transfer of these mutant vectors in vivo resulted in higher vector copy numbers (up to 4.9-fold) and transgene expression (up to 14-fold) than observed from the AAV2-WT vector. One of the mutant vectors, S489A, generated similar to 8-fold fewer antibodies that could be cross-neutralized by AAV2-WT. This study thus demonstrates the feasibility of the use of these novel AAV2 capsid mutant vectors in hepatic gene therapy.

Simvastatin Induced Neurite Outgrowth Unveils Role of Cell Surface Cholesterol and Acetyl CoA Carboxylase in SH-SY5Y Cells

Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated protein kinase (AMPK) in nonneural cells; however no study demonstrates whether CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2 protein expression / localization and phosphorylation of various receptor tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that SIN is critically dependent on this CSC. Simultaneously, phospho array for mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM led to a transient increase in AMPK phosphorylation followed by a sudden decline; the effect was independent of PI3K. Strikingly, AMPK phosphorylation was regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM treatment as evidenced by increase in threonine phosphorylation. Moreover, it was observed that addition of AMP analogue and PP2A inhibitor inhibited SIN. Biocomposition of neurites shows that lipids form a major part of neurites and AMPK is known to regulate lipid metabolism majorly through acetyl CoA carboxylase (ACC). AMPK activity is negative regulator of ACC activity and we found that phosphorylation of ACC started to decrease after 6 hrs which becomes more pronounced at 12 hrs. Addition of ACC inhibitor showed that SIN is dependent on ACC activity. Simultaneously, addition of Fatty acid synthase (FAS) inhibitor confirmed that endogenous lipid pathway is important for SIN. We further investigated SREBP-1 pathway activation which controls ACC and FAS at transcriptional level. However, SIM did not affect SREBP-1 processing and transcription of its target genes likes ACC1 and FAS. In conclusion, this study highlights a distinct role of CSC and ACC in SIN which might have implication in process of neuronal differentiation induced by other agents.

Structures of substrate- and nucleotide-bound propionate kinase from Salmonella typhimurium: substrate specificity and phosphate-transfer mechanism

Kinases are ubiquitous enzymes that are pivotal to many biochemical processes. There are contrasting views on the phosphoryl-transfer mechanism in propionate kinase, an enzyme that reversibly transfers a phosphoryl group from propionyl phosphate to ADP in the final step of non-oxidative catabolism of L-threonine to propionate. Here, X-ray crystal structures of propionate- and nucleotide-bound Salmonella typhimurium propionate kinase are reported at 1.8-2.0 angstrom resolution. Although the mode of nucleotide binding is comparable to those of other members of the ASKHA superfamily, propionate is bound at a distinct site deeper in the hydrophobic pocket defining the active site. The propionate carboxyl is at a distance of approximate to 5 angstrom from the -phosphate of the nucleotide, supporting a direct in-line transfer mechanism. The phosphoryl-transfer reaction is likely to occur via an associative S(N)2-like transition state that involves a pentagonal bipyramidal structure with the axial positions occupied by the nucleophile of the substrate and the O atom between the - and the -phosphates, respectively. The proximity of the strictly conserved His175 and Arg236 to the carboxyl group of the propionate and the -phosphate of ATP suggests their involvement in catalysis. Moreover, ligand binding does not induce global domain movement as reported in some other members of the ASKHA superfamily. Instead, residues Arg86, Asp143 and Pro116-Leu117-His118 that define the active-site pocket move towards the substrate and expel water molecules from the active site. The role of Ala88, previously proposed to be the residue determining substrate specificity, was examined by determining the crystal structures of the propionate-bound Ala88 mutants A88V and A88G. Kinetic analysis and structural data are consistent with a significant role of Ala88 in substrate-specificity determination. The active-site pocket-defining residues Arg86, Asp143 and the Pro116-Leu117-His118 segment are also likely to contribute to substrate specificity.

DECT evaluation of noncalc fied coronary artery plaque

Purpose: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (rho(e)) and the effective atomic number (Z(eff)) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. Methods: For the purpose of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (rho(e), Z(eff)) lie in the range of (2.65 x 10(23) <= rho(e) <= 3.64 x 10(23)/cm(3)) and (6.80 <= Z(eff) <= 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V-1) and HU(V-2), with V-1,V-2 = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (rho(e), Z(eff)) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (rho(e), Z(eff)) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. Results: The authors find that the calibration gives Pc with an accuracy of 3.5% while Z(eff) is found within 1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques are practically nonexistent, and microcalcification, as observed in histopathology, has to be taken into account to explain the nature of the observed (rho(e), Z(eff)) data. This also enables us to judge the composition of the plaque in terms of basic model which considers the plaque to be composed of fibres, lipids, and microcalcification. Conclusions: This simple and reliable method has the potential as an effective modality to investigate the composition of noncalcified coronary artery plaques and thus help in their characterization. In this inversion method, (rho(e), Z(eff)) of the scanned sample can be found by eliminating the effects of the CT machine and also by ensuring that the determination of the two unknowns (rho(e), Z(eff)) does not interfere with each other and the nature of the plaque can be identified in terms of a three component model. (C) 2015 American Association of Physicists in Medicine.

Efficient density matrix renormalization group algorithm to study Y junctions with integer and half-integer spin

An efficient density matrix renormalization group (DMRG) algorithm is presented and applied to Y junctions, systems with three arms of n sites that meet at a central site. The accuracy is comparable to DMRG of chains. As in chains, new sites are always bonded to the most recently added sites and the superblock Hamiltonian contains only new or once renormalized operators. Junctions of up to N = 3n + 1 approximate to 500 sites are studied with antiferromagnetic (AF) Heisenberg exchange J between nearest-neighbor spins S or electron transfer t between nearest neighbors in half-filled Hubbard models. Exchange or electron transfer is exclusively between sites in two sublattices with N-A not equal N-B. The ground state (GS) and spin densities rho(r) = < S-r(z)> at site r are quite different for junctions with S = 1/2, 1, 3/2, and 2. The GS has finite total spin S-G = 2S(S) for even (odd) N and for M-G = S-G in the S-G spin manifold, rho(r) > 0(< 0) at sites of the larger (smaller) sublattice. S = 1/2 junctions have delocalized states and decreasing spin densities with increasing N. S = 1 junctions have four localized S-z = 1/2 states at the end of each arm and centered on the junction, consistent with localized states in S = 1 chains with finite Haldane gap. The GS of S = 3/2 or 2 junctions of up to 500 spins is a spin density wave with increased amplitude at the ends of arms or near the junction. Quantum fluctuations completely suppress AF order in S = 1/2 or 1 junctions, as well as in half-filled Hubbard junctions, but reduce rather than suppress AF order in S = 3/2 or 2 junctions.

Localized Charge Carrier Transport Properties of Zn1-x Ni (x) O/NiO Two-Phase Composites

We report the localized charge carrier transport of two-phase composite Zn1-x Ni (x) O/NiO (0 a parts per thousand currency sign x a parts per thousand currency sign 1) using the temperature dependence of ac-resistivity rho (ac)(T) across the N,el temperature T (N) (= 523 K) of nickel oxide. Our results provide strong evidence to the variable range hopping of charge carriers between the localized states through a mechanism involving spin-dependent activation energies. The temperature variation of carrier hopping energy epsilon (h)(T) and nearest-neighbor exchange-coupling parameter J (ij)(T) evaluated from the small poleron model exhibits a well-defined anomaly across T (N). For all the composite systems, the average exchange-coupling parameter (J (ij))(AVG) nearly equals to 70 meV which is slightly greater than the 60-meV exciton binding energy of pure zinc oxide. The magnitudes of epsilon (h) (similar to 0.17 eV) and J (ij) (similar to 11 meV) of pure NiO synthesized under oxygen-rich conditions are consistent with the previously reported theoretical estimation based on Green's function analysis. A systematic correlation between the oxygen stoichiometry and, epsilon (h)(T) and J (ij)(T) is discussed.

Structure-rheology relationship in a sheared lamellar fluid

The structure-rheology relationship in the shear alignment of a lamellar fluid is studied using a mesoscale model which provides access to the lamellar configurations and the rheology. Based on the equations and free energy functional, the complete set of dimensionless groups that characterize the system are the Reynolds number (rho gamma L-2/mu), the Schmidt number (mu/rho D), the Ericksen number (mu(gamma)/B), the interface sharpness parameter r, the ratio of the viscosities of the hydrophilic and hydrophobic parts mu(r), and the ratio of the system size and layer spacing (L/lambda). Here, rho and mu are the fluid density and average viscosity, (gamma) over dot is the applied strain rate, D is the coefficient of diffusion, B is the compression modulus, mu(r) is the maximum difference in the viscosity of the hydrophilic and hydrophobic parts divided by the average viscosity, and L is the system size in the cross-stream direction. The lattice Boltzmann method is used to solve the concentration and momentum equations for a two dimensional system of moderate size (L/lambda = 32) and for a low Reynolds number, and the other parameters are systematically varied to examine the qualitative features of the structure and viscosity evolution in different regimes. At low Schmidt numbers where mass diffusion is faster than momentum diffusion, there is fast local formation of randomly aligned domains with ``grain boundaries,'' which are rotated by the shear flow to align along the extensional axis as time increases. This configuration offers a high resistance to flow, and the layers do not align in the flow direction even after 1000 strain units, resulting in a viscosity higher than that for an aligned lamellar phase. At high Schmidt numbers where momentum diffusion is fast, the shear flow disrupts layers before they are fully formed by diffusion, and alignment takes place by the breakage and reformation of layers by shear, resulting in defects (edge dislocations) embedded in a background of nearly aligned layers. At high Ericksen number where the viscous forces are large compared to the restoring forces due to layer compression and bending, shear tends to homogenize the concentration field, and the viscosity decreases significantly. At very high Ericksen number, shear even disrupts the layering of the lamellar phase. At low Ericksen number, shear results in the formation of well aligned layers with edge dislocations. However, these edge dislocations take a long time to anneal; the relatively small misalignment due to the defects results in a large increase in viscosity due to high layer stiffness and due to shear localization, because the layers between defects get pinned and move as a plug with no shear. An increase in the viscosity contrast between the hydrophilic and hydrophobic parts does not alter the structural characteristics during alignment. However, there is a significant increase in the viscosity, due to pinning of the layers between defects, which results in a plug flow between defects and a localization of the shear to a part of the domain.