Simultaneous co-ordination of three cytosine ligands displaying different binding sites around the copper centres

We report the synthesis and structural characterization of a polymeric ternary copper-cytosine-phenanthroline complex, Cu-4(phen)(3)-(mu(3)-cyt)(2)(mu-OH)(cyt)(OH)Cl-3](n)center dot 16H(2)O, where three cytosine ligands with different binding sites have simultaneously complexed to the four copper metal centres. Interestingly, the complex exhibits two different coordination geometries around the metal centres.

Synthesis, DNA binding, docking and photocleavage studies of quinolinyl chalcones

A series of simple quinoline-chalcone conjugates have been synthesized by Claisen-Schmidt condensation reactions of substituted acetophenones with 2-chloro-3-formyl-quinoline and evaluated for their nucleolytic activity. The structures of the synthesized quinoline-chalcone conjugates were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral analyses. Most of the prepared compounds showed significant DNA binding and photocleavage activities. The incorporation of an electron-donating group into ring A caused a moderate increase in the DNA binding and photocleavage activities. Compounds 3c and 3d exhibited promising DNA photocleavage against pUC 19 DNA with 85% inhibition at 100 mu M concentration. A structure-activity relationship analysis of these compounds was performed; compounds 3c and 3d are potential candidates for future drug discovery and development.

A general methodology for calculating mixed mode stress intensity factors and fracture toughness of solder joints with interfacial cracks

Solder joints in electronic packages undergo thermo-mechanical cycling, resulting in nucleation of micro-cracks, especially at the solder/bond-pad interface, which may lead to fracture of the joints. The fracture toughness of a solder joint depends on material properties, process conditions and service history, as well as strain rate and mode-mixity. This paper reports on a methodology for determining the mixed-mode fracture toughness of solder joints with an interfacial starter-crack, using a modified compact mixed mode (CMM) specimen containing an adhesive joint. Expressions for stress intensity factor (K) and strain energy release rate (G) are developed, using a combination of experiments and finite element (FE) analysis. In this methodology, crack length dependent geometry factors to convert for the modified CMM sample are first obtained via the crack-tip opening displacement (CTOD)-based linear extrapolation method to calculate the under far-field mode I and II conditions (f(1a) and f(2a)), (ii) generation of a master-plot to determine a(c), and (iii) computation of K and G to analyze the fracture behavior of joints. The developed methodology was verified using J-integral calculations, and was also used to calculate experimental fracture toughness values of a few lead-free solder-Cu joints. (C) 2014 Elsevier Ltd. All rights reserved.

Tailoring the second mode of Euler-Bernoulli beams: an analytical approach

In this paper, we study the inverse mode shape problem for an Euler-Bernoulli beam, using an analytical approach. The mass and stiffness variations are determined for a beam, having various boundary conditions, which has a prescribed polynomial second mode shape with an internal node. It is found that physically feasible rectangular cross-section beams which satisfy the inverse problem exist for a variety of boundary conditions. The effect of the location of the internal node on the mass and stiffness variations and on the deflection of the beam is studied. The derived functions are used to verify the p-version finite element code, for the cantilever boundary condition. The paper also presents the bounds on the location of the internal node, for a valid mass and stiffness variation, for any given boundary condition. The derived property variations, corresponding to a given mode shape and boundary condition, also provides a simple closed-form solution for a class of non-uniform Euler-Bernoulli beams. These closed-form solutions can also be used to check optimization algorithms proposed for modal tailoring.

Sliding Mode Control-Based Autopilots for Leaderless Consensus of Unmanned Aerial Vehicles

In this brief, decentralized sliding mode controllers that enable a connected and leaderless swarm of unmanned aerial vehicles (UAVs) to reach a consensus in altitude and heading angle are presented. In addition, sliding mode control-based autopilot designs to control those states for which consensus is not required are also presented. By equipping each UAV with this combination of controllers, it can autonomously decide on being a member of the swarm or fly independently. The controllers are designed using a coupled nonlinear dynamic model, derived for the YF-22 aircraft, where the aerodynamic forces and moments are linear functions of the states and inputs.

Chemical specificity and conformational flexibility in proteinase-inhibitor interaction: Scaffolds for promiscuous binding

One of the most important roles of proteins in cellular milieu is recognition of other biomolecules including other proteins. Protein protein complexes are involved in many essential cellular processes. Interfaces of protein protein complexes are traditionally known to be conserved in evolution and less flexible than other solvent interacting tertiary structural surface. But many examples are emerging where these features do not hold good. An understanding of inter-play between flexibility and sequence conservation is emerging, providing a fresh dimension to the paradigm of sequence structure function relationship. The functional manifestation of the inter-relation between sequence conservation and flexibility of interface is exemplified in this review using proteinase inhibitor protein complexes. (C) 2014 Elsevier Ltd. All rights reserved.

Synthesis and crystal structure of copper (II) uracil ternary polymeric complex with 1,10-phenanthroline along with the Hirshfeld surface analysis of the metal binding sites for the uracil ligand

The study of models for ``metal-enzyme-substrate'' interaction has been a proactive area of research owing to its biological and pharmacological importance. In this regard the ternary copper uracil complex with 1,10-phenanthroline represents metal-enzyme-substrate system for DNA binding enzymes. The synthesis of the complex, followed by slow evaporation of the reaction mixture forms two concomitant solvatomorph crystals viz., {Cu(phen)(mu-ura)(H2O)](n)center dot H2O (1a)} and {Cu(phen)(mu-ura)(H2O)](n)center dot CH3OH (1b)}. Both complexes are structurally characterized, while elemental analysis, IR and EPR spectra were recorded for 1b (major product). In both complexes, uracil coordinates uniquely via N1 and N3 nitrogen atom acting as a bidentate bridging ligand forming a 1-D polymer. The two solvatomorphs were quantitatively analyzed for the differences with the aid of Hirshfeld surface analysis. (C) 2014 Elsevier B.V. All rights reserved.

Wall-mode instability in plane shear flow of viscoelastic fluid over a deformable solid

The linear stability analysis of a plane Couette flow of an Oldroyd-B viscoelastic fluid past a flexible solid medium is carried out to investigate the role of polymer addition in the stability behavior. The system consists of a viscoelastic fluid layer of thickness R, density rho, viscosity eta, relaxation time lambda, and retardation time beta lambda flowing past a linear elastic solid medium of thickness HR, density rho, and shear modulus G. The emphasis is on the high-Reynolds-number wall-mode instability, which has recently been shown in experiments to destabilize the laminar flow of Newtonian fluids in soft-walled tubes and channels at a significantly lower Reynolds number than that for flows in rigid conduits. For Newtonian fluids, the linear stability studies have shown that the wall modes become unstable when flow Reynolds number exceeds a certain critical value Re c which scales as Sigma(3/4), where Reynolds number Re = rho VR/eta, V is the top-plate velocity, and dimensionless parameter Sigma = rho GR(2)/eta(2) characterizes the fluid-solid system. For high-Reynolds-number flow, the addition of polymer tends to decrease the critical Reynolds number in comparison to that for the Newtonian fluid, indicating a destabilizing role for fluid viscoelasticity. Numerical calculations show that the critical Reynolds number could be decreased by up to a factor of 10 by the addition of small amount of polymer. The critical Reynolds number follows the same scaling Re-c similar to Sigma(3/4) as the wall modes for a Newtonian fluid for very high Reynolds number. However, for moderate Reynolds number, there exists a narrow region in beta-H parametric space, corresponding to very dilute polymer solution (0.9 less than or similar to beta < 1) and thin solids (H less than or similar to 1.1), in which the addition of polymer tends to increase the critical Reynolds number in comparison to the Newtonian fluid. Thus, Reynolds number and polymer properties can be tailored to either increase or decrease the critical Reynolds number for unstable modes, thus providing an additional degree of control over the laminar-turbulent transition.

Common-Mode Injection PWM for Parallel Converters

The ac-side terminal voltages of parallel-connected converters are different if the line reactive drops of the individual converters are different. This could result either from differences in per-phase inductances or from differences in the line currents of the converters. In such cases, the modulating signals are different for the converters. Hence, the common-mode (CM) voltages for the converters, injected by conventional space vector pulsewidth modulation (CSVPWM) to increase dc-bus utilization, are different. Consequently, significant low-frequency zero-sequence circulating currents result. This paper proposes a new modulation method for parallel-connected converters with unequal terminal voltages. This method does not cause low-frequency zero-sequence circulating currents and is comparable with CSVPWM in terms of dc-bus utilization and device power loss. Experimental results are presented at a power level of 150 kVA from a circulating-power test setup, where the differences in converter terminal voltages are quite significant.

Remarkable visible light-triggered cytotoxicity of mitochondria targeting mixed-ligand cobalt(III) complexes of curcumin and phenanthroline bases binding to human serum albumin

Six new mixed-ligand cobalt(III) complexes of formulation Co(N-N)(2)(O-O)](ClO4)(2) (1-6), where N-N is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 2), dipyrido3,2-d:2',3'-f] quinoxaline (dpq in 3, 4), and dipyrido3,2-a:2',3'-c]phenazine (dppz in 5, 6), O-O is acetylacetonate (acac in 1, 3, 5) or curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, cur in 2, 4, 6), have been synthesized and characterized. The X-ray crystal structures of complex 1 (as PF6- salt, 1a) and 3 show distorted octahedral geometries formed by the CoN4O2 core. The complexes 1, 3 and 5 having the simple acac ligand are prepared as control species to understand the role of curcumin. The optimized geometries and the frontier orbitals of the curcumin complexes 2, 4, and 6 are obtained from the DFT calculations. The complexes 2, 4, and 6 having the photoactive curcumin moiety display an absorption band in the visible region near 420 nm and show remarkable photocytotoxicity in HeLa cancer cells with respective IC50 values of 7.4 mu M, 5.1 mu M and 1.6 mu M while being much less toxic in dark. MTT assay using complex 6 shows that it is not significantly photocytotoxic to MCF-10A normal cells. The control complexes having the acac ligand are non-toxic both in the presence and absence of light. The cell death is apoptotic in nature and triggered by the photogeneration of reactive oxygen species. Fluorescence imaging experiments on HeLa cells reveals that complex 6 accumulated primarily inside the mitochondria. Human serum albumin (HSA) binding experiments show that the complexes bind HSA with good affinity, but 6 binds with the highest affinity, with a K-b value of 9.8 x 10(5) M-1. Thus, complex 6 with its negligible toxicity in the dark and in normal cells but remarkable toxicity in visible light holds significant photochemotherapeutic potential.

Three Dimensional Impact Angle Constrained Guidance Law using Sliding Mode Control

In this paper, three dimensional impact angle control guidance laws are proposed for stationary targets. Unlike the usual approach of decoupling the engagement dynamics into two mutually orthogonal 2-dimensional planes, the guidance laws are derived using the coupled dynamics. These guidance laws are designed using principles of conventional as well as nonsingular terminal sliding mode control theory. The guidance law based on nonsingular terminal sliding mode guarantees finite time convergence of interceptor to the desired impact angle. In order to derive the guidance laws, multi-dimension switching surfaces are used. The stability of the system, with selected switching surfaces, is demonstrated using Lyapunov stability theory. Numerical simulation results are presented to validate the proposed guidance law.

Water Dispersible, Positively and Negatively Charged MoS2 Nanosheets: Surface Chemistry and the Role of Surfactant Binding

Stable aqueous dispersions of atomically thin layered MoS2 nanosheets have been obtained by sonication in the presence of ionic surfactants. The dispersions are stabilized by electrostatic repulsion between the sheets, and we show that the sign of the charge on the MoS2 nanosheets, either positive or negative, can be can be controlled by the choice of the surfactant. Using techniques from solution NMR, we show that the surfactant chains are weakly bound to the MoS2 sheets and undergo rapid exchange with free surfactant chains present in the dispersion. In situ nuclear Overhauser effect spectroscopic measurements provide direct evidence that the surfactant chains lie flat, arranged randomly on the basal plane of the MoS2 nanosheets with their charged headgroup exposed. These results provide a chemical perspective for understanding the stability of these inorganic nanosheets in aqueous dispersions and the origin of the charge on the sheets.

The cold mode: a phenomenological model for the evolution of density perturbations in the intracluster medium

Cool cluster cores are in global thermal equilibrium but are locally thermally unstable. We study a non-linear phenomenological model for the evolution of density perturbations in the intracluster medium (ICM) due to local thermal instability and gravity. We have analysed and extended a model for the evolution of an overdense blob in the ICM. We find two regimes in which the overdense blobs can cool to thermally stable low temperatures. One for large t(cool)/t(ff) (t(cool) is the cooling time and t(ff) is the free-fall time), where a large initial overdensity is required for thermal runaway to occur; this is the regime which was previously analysed in detail. We discover a second regime for t(cool)/t(ff) less than or similar to 1 (in agreement with Cartesian simulations of local thermal instability in an external gravitational field), where runaway cooling happens for arbitrarily small amplitudes. Numerical simulations have shown that cold gas condenses out more easily in a spherical geometry. We extend the analysis to include geometrical compression in weakly stratified atmospheres such as the ICM. With a single parameter, analogous to the mixing length, we are able to reproduce the results from numerical simulations; namely, small density perturbations lead to the condensation of extended cold filaments only if t(cool)/t(ff) less than or similar to 10.

Remarkable enhancement in photocytotoxicity and hydrolytic stability of curcumin on binding to an oxovanadium(IV) moiety

Oxovanadium(IV) complexes of polypyridyl and curcumin-based ligands, viz. VO(cur)(L)Cl] (1, 2) and VO(scur)(L)Cl] (3, 4), where L is 1,10-phenanthroline (phen in 1 and 3), dipyrido3,2-a:2',3'-c]phenazine (dppz in 2 and 4), Hcur is curcumin and Hscur is diglucosylcurcumin, were synthesized and characterized and their cellular uptake, photocytotoxicity, intracellular localization, DNA binding, and DNA photo-cleavage activity studied. Complex VO(cur)(phen)Cl] (1) has (VN2O3Cl)-N-IV distorted octahedral geometry as evidenced from its crystal structure. The sugar appended complexes show significantly higher uptake into the cancer cells compared to their normal analogues. The complexes are remarkably photocytotoxic in visible light (400-700 nm) giving an IC50 value of <5 mu M in HeLa, HaCaT and MCF-7 cells with no significant dark toxicity. The green emission of the complexes was used for cellular imaging. Predominant cytosolic localization of the complexes 1-4 to a lesser extent into the nucleus was evidenced from confocal imaging. The complexes as strong binders of calf thymus DNA displayed photocleavage of supercoiled pUC19 DNA in red light by generating (OH)-O-center dot radicals as the ROS. The cell death is via an apoptotic pathway involving the ROS. Binding to the VO2+ moiety has resulted in stability against any hydrolytic degradation of curcumin along with an enhancement of its photocytotoxicity.

A Gaussian network model study suggests that structural fluctuations are higher for inactive states than active states of protein kinases

We performed Gaussian network model based normal mode analysis of 3-dimensional structures of multiple active and inactive forms of protein kinases. In 14 different kinases, a more number of residues (1095) show higher structural fluctuations in inactive states than those in active states (525), suggesting that, in general, mobility of inactive states is higher than active states. This statistically significant difference is consistent with higher crystallographic B-factors and conformational energies for inactive than active states, suggesting lower stability of inactive forms. Only a small number of inactive conformations with the DFG motif in the ``in'' state were found to have fluctuation magnitudes comparable to the active conformation. Therefore our study reports for the first time, intrinsic higher structural fluctuation for almost all inactive conformations compared to the active forms. Regions with higher fluctuations in the inactive states are often localized to the aC-helix, aG-helix and activation loop which are involved in the regulation and/or in structural transitions between active and inactive states. Further analysis of 476 kinase structures involved in interactions with another domain/protein showed that many of the regions with higher inactive-state fluctuation correspond to contact interfaces. We also performed extensive GNM analysis of (i) insulin receptor kinase bound to another protein and (ii) holo and apo forms of active and inactive conformations followed by multi-factor analysis of variance. We conclude that binding of small molecules or other domains/proteins reduce the extent of fluctuation irrespective of active or inactive forms. Finally, we show that the perceived fluctuations serve as a useful input to predict the functional state of a kinase.