Sensitivity of Water Dynamics to Biologically Significant Surfaces of Monomeric Insulin: Role of Topology and Electrostatic Interactions

In addition to the biologically active monomer of the protein insulin circulating in human blood, the molecule also exists in dimeric and hexameric forms that are used as storage. The insulin monomer contains two distinct surfaces, namely, the dimer forming surface (DFS) and the hexamer forming surface (HFS), that are specifically designed to facilitate the formation of the dimer and the hexamer, respectively. In order to characterize the structural and dynamical behavior of interfacial water molecules near these two surfaces (DFS and HFS), we performed atomistic molecular dynamics simulations of insulin with explicit water. Dynamical characterization reveals that the structural relaxation of the hydrogen bonds formed between the residues of DFS and the interfacial water molecules is faster than those formed between water and that of the HFS. Furthermore, the residence times of water molecules in the protein hydration layer for both the DFS and HFS are found to be significantly higher than those for some of the other proteins studied so far, such as HP-36 and lysozyme. In particular, we find that more structured water molecules, with higher residence times (similar to 300-500 ps), are present near HFS than those near DFS. A significant slowing down is observed in the decay of associated rotational auto time correlation functions of O-H bond vector of water in the vicinity of HFS. The surface topography and the arrangement of amino acid residues work together to organize the water molecules in the hydration layer in order to provide them with a preferred orientation. HFS having a large polar solvent accessible surface area and a convex extensive nonpolar region, drives the surrounding water molecules to acquire predominantly an outward H-atoms directed, clathrate-like structure. In contrast, near the DFS, the surrounding water molecules acquire an inward H-atoms directed orientation owing to the flat curvature of hydrophobic surface and the interrupted hydrophilic residual alignment. We have followed escape trajectory of several such quasi-bound water molecules from both the surfaces that reveal the significant differences between the two hydration layers.

Solving Axisymmetric Stability Problems by Using Upper Bound Finite Elements, Limit Analysis, and Linear Optimization

A numerical formulation has been proposed for solving an axisymmetric stability problem in geomechanics with upper bound limit analysis, finite elements, and linear optimization. The Drucker-Prager yield criterion is linearized by simulating a sphere with a circumscribed truncated icosahedron. The analysis considers only the velocities and plastic multiplier rates, not the stresses, as the basic unknowns. The formulation is simple to implement, and it has been employed for finding the collapse loads of a circular footing placed over the surface of a cohesive-frictional material. The formulation can be used to solve any general axisymmetric geomechanics stability problem.

Effect of the Flow Rule on the Bearing Capacity of Strip Foundations on Sand by the Upper-Bound Limit Analysis and Slip Lines

The influence of the flow rule on the bearing capacity of strip foundations placed on sand was investigated using a new kinematic approach of upper-bound limit analysis. The method of stress characteristics was first used to find the mechanism of the failure and to compute the stress field by using the Mohr-Coulomb yield criterion. Once the failure mechanism had been established, the kinematics of the plastic deformation was established, based on the requirements of the upper-bound limit theorem. Both associated and nonassociated plastic flows were considered, and the bearing capacity was obtained by equating the rate of external plastic work to the rate of the internal energy dissipation for both smooth and rough base foundations. The results obtained from the analysis were compared with those available from the literature. (C) 2014 American Society of Civil Engineers.

Upper Bounds on the Size of Grain-Correcting Codes

In this paper, we revisit the combinatorial error model of Mazumdar et al. that models errors in high-density magnetic recording caused by lack of knowledge of grain boundaries in the recording medium. We present new upper bounds on the cardinality/rate of binary block codes that correct errors within this model. All our bounds, except for one, are obtained using combinatorial arguments based on hypergraph fractional coverings. The exception is a bound derived via an information-theoretic argument. Our bounds significantly improve upon existing bounds from the prior literature.

Molecular topology of three ring nematogens from C-13-H-1 dipolar couplings

Molecules in their liquid crystalline phase undergo rotational motion about the long axis of the molecule and the shape adopted by the rotating molecule plays an important role in influencing the mesophase morphology. In this context, obtaining the topology and the relative orientation of the different sub-units are important steps. For studying the liquid crystalline phase, C-13 NMR spectroscopy is a convenient method and for certain specifically designed nematogens, 2-dimensional separated local field (2D-SLF) NMR spectroscopy provides a particularly simple and straightforward means of arriving at the molecular topology. We demonstrate this approach on two three ring based nematogens designed with a phenyl or a thiophene ring at one of the termini. From the C-13-H-1 dipolar couplings of the terminal carbon obtained using the 2D-SLF NMR technique, the order parameter of the local symmetry axis of the terminal phenyl ring as well as of the long molecular axis could be easily estimated. For the thiophene nematogen, the lack of symmetry of the thiophene moiety necessitates some additional computational steps. The results indicate that the thiophene unit has its local ordering axis oriented away from the long molecular axis by a small angle, consistent with a bent structure expected in view of the thiophene geometry. The experiment also demonstrates the ability of 2D-SLF NMR to provide high resolution spectra by separation of several overlapped resonances in terms of their C-13-H-1 dipolar couplings. The results are consistent with a rod-like topology of the core of the investigated mesogens. The investigation demonstrates the potential of 2D-SLF NMR C-13 spectroscopy for obtaining atomistic level information and its utility for topological studies of different mesogens.

A Comparison of Machine Learning Techniques for Modeling River Flow Time Series: The Case of Upper Cauvery River Basin

Models of river flow time series are essential in efficient management of a river basin. It helps policy makers in developing efficient water utilization strategies to maximize the utility of scarce water resource. Time series analysis has been used extensively for modeling river flow data. The use of machine learning techniques such as support-vector regression and neural network models is gaining increasing popularity. In this paper we compare the performance of these techniques by applying it to a long-term time-series data of the inflows into the Krishnaraja Sagar reservoir (KRS) from three tributaries of the river Cauvery. In this study flow data over a period of 30 years from three different observation points established in upper Cauvery river sub-basin is analyzed to estimate their contribution to KRS. Specifically, ANN model uses a multi-layer feed forward network trained with a back-propagation algorithm and support vector regression with epsilon intensive-loss function is used. Auto-regressive moving average models are also applied to the same data. The performance of different techniques is compared using performance metrics such as root mean squared error (RMSE), correlation, normalized root mean squared error (NRMSE) and Nash-Sutcliffe Efficiency (NSE).

Interpreting the upper level structure of the Madden-Julian oscillation

The nonlinear response of a spherical shallow water model to an imposed heat source in the presence of realistic zonal mean zonal winds is investigated numerically. The solutions exhibit elongated, meridionally tilted ridges and troughs indicative of a poleward dispersion of wave activity. As the speed of the jets is increased, the equatorial Kelvin wave is unaffected but the global Rossby wave train coalesces to form a compact, amplified quadrupole structure that bears a striking resemblance to the observed upper level structure of the Madden-Julian oscillation. In the presence of strong subtropical westerly jets, the advection of planetary vorticity by the meridional flow and relative vorticity by the zonally averaged background flow conspire to create the distinctive quadrupole configuration of flanking Rossby waves.

Flexible implementation of power system corrective topology control

This paper proposes a novel decision making framework for optimal transmission switching satisfying the AC feasibility, stability and circuit breaker (CB) reliability requirements needed for practical implementation. The proposed framework can be employed as a corrective tool in day to day operation planning scenarios in response to potential contingencies. The switching options are determined using an efficient heuristic algorithm based on DC optimal power flow, and are presented in a multi-branch tree structure. Then, the AC feasibility and stability checks are conducted and the CB condition monitoring data are employed to perform a CB reliability and line availability assessment. Ultimately, the operator will be offered multiple AC feasible and stable switching options with associated benefits. The operator can use this information, other operating conditions not explicitly considered in the optimization, and his/her own experience to implement the best and most reliable switching action(s). The effectiveness of the proposed approach is validated on the IEEE-118 bus test system. (C) 2015 Elsevier B.V. All rights reserved.

Bearing capacity factors for a conical footing using lower- and upper-bound finite elements limit analysis

Bearing capacity factors, N-c, N-q, and N-gamma, for a conical footing are determined by using the lower and upper bound axisymmetric formulation of the limit analysis in combination with finite elements and optimization. These factors are obtained in a bound form for a wide range of the values of cone apex angle (beta) and phi with delta = 0, 0.5 phi, and phi. The bearing capacity factors for a perfectly rough (delta = phi) conical footing generally increase with a decrease in beta. On the contrary, for delta = 0 degrees, the factors N-c and N-q reduce gradually with a decrease in beta. For delta = 0 degrees, the factor N-gamma for phi >= 35 degrees becomes a minimum for beta approximate to 90 degrees. For delta = 0 degrees, N-gamma for phi <= 30 degrees, as in the case of delta = phi, generally reduces with an increase in beta. The failure and nodal velocity patterns are also examined. The results compare well with different numerical solutions and centrifuge tests' data available from the literature.

Upper bound on cubicity in terms of boxicity for graphs of low chromatic number

The boxicity (respectively cubicity) of a graph G is the least integer k such that G can be represented as an intersection graph of axis-parallel k-dimensional boxes (respectively k-dimensional unit cubes) and is denoted by box(G) (respectively cub(G)). It was shown by Adiga and Chandran (2010) that for any graph G, cub(G) <= box(G) log(2) alpha(G], where alpha(G) is the maximum size of an independent set in G. In this note we show that cub(G) <= 2 log(2) X (G)] box(G) + X (G) log(2) alpha(G)], where x (G) is the chromatic number of G. This result can provide a much better upper bound than that of Adiga and Chandran for graph classes with bounded chromatic number. For example, for bipartite graphs we obtain cub(G) <= 2(box(G) + log(2) alpha(G)] Moreover, we show that for every positive integer k, there exist graphs with chromatic number k such that for every epsilon > 0, the value given by our upper bound is at most (1 + epsilon) times their cubicity. Thus, our upper bound is almost tight. (c) 2015 Elsevier B.V. All rights reserved.

MS3ALIGN: an efficient molecular surface aligner using the topology of surface curvature

Background: Aligning similar molecular structures is an important step in the process of bio-molecular structure and function analysis. Molecular surfaces are simple representations of molecular structure that are easily constructed from various forms of molecular data such as 3D atomic coordinates (PDB) and Electron Microscopy (EM) data. Methods: We present a Multi-Scale Morse-Smale Molecular-Surface Alignment tool, MS3ALIGN, which aligns molecular surfaces based on significant protrusions on the molecular surface. The input is a pair of molecular surfaces represented as triangle meshes. A key advantage of MS3ALIGN is computational efficiency that is achieved because it processes only a few carefully chosen protrusions on the molecular surface. Furthermore, the alignments are partial in nature and therefore allows for inexact surfaces to be aligned. Results: The method is evaluated in four settings. First, we establish performance using known alignments with varying overlap and noise values. Second, we compare the method with SurfComp, an existing surface alignment method. We show that we are able to determine alignments reported by SurfComp, as well as report relevant alignments not found by SurfComp. Third, we validate the ability of MS3ALIGN to determine alignments in the case of structurally dissimilar binding sites. Fourth, we demonstrate the ability of MS3ALIGN to align iso-surfaces derived from cryo-electron microscopy scans. Conclusions: We have presented an algorithm that aligns Molecular Surfaces based on the topology of surface curvature. Awebserver and standalone software implementation of the algorithm available at http://vgl.serc.iisc.ernet. in/ms3align.

Reduced common-mode voltage operation of a new seven-level hybrid multilevel inverter topology with a single DC voltage source

In this study, analysis of extending the linear modulation range of a zero common-mode voltage (CMV) operated n-level inverter by allowing reduced CMV switching is presented. A new hybrid seven-level inverter topology with a single DC supply is also presented in this study and inverter operation for zero and reduced CMV is analysed. Each phase of the inverter is realised by cascading two three-level flying capacitor inverters with a half-bridge module in between. Proposed inverter topology is operated with zero CMV for modulation index <86% and is operated with a CMV magnitude of V-dc/18 to extend the modulation range up to 96%. Experimental results are presented for zero CMV operation and for reduced common voltage operation to extend the linear modulation range. A capacitor voltage balancing algorithm is designed utilising the pole voltage redundancies of the inverter, which works for every sampling instant to correct the capacitor voltage irrespective of load power factor and modulation index. The capacitor voltage balancing algorithm is tested for different modulation indices and for various transient conditions, to validate the proposed topology.