Common recognition principles across diverse sequence and structural families of sialic acid binding proteins

Sialic acids form a large family of 9-carbon monosaccharides and are integral components of glycoconjugates. They are known to bind to a wide range of receptors belonging to diverse sequence families and fold classes and are key mediators in a plethora of cellular processes. Thus, it is of great interest to understand the features that give rise to such a recognition capability. Structural analyses using a non-redundant data set of known sialic acid binding proteins was carried out, which included exhaustive binding site comparisons and site alignments using in-house algorithms, followed by clustering and tree computation, which has led to derivation of sialic acid recognition principles. Although the proteins in the data set belong to several sequence and structure families, their binding sites could be grouped into only six types. Structural comparison of the binding sites indicates that all sites contain one or more different combinations of key structural features over a common scaffold. The six binding site types thus serve as structural motifs for recognizing sialic acid. Scanning the motifs against a non-redundant set of binding sites from PDB indicated the motifs to be specific for sialic acid recognition. Knowledge of determinants obtained from this study will be useful for detecting function in unknown proteins. As an example analysis, a genome-wide scan for the motifs in structures of Mycobacterium tuberculosis proteome identified 17 hits that contain combinations of the features, suggesting a possible function of sialic acid binding by these proteins.

First-principles DFT plus GW study of oxygen vacancies in rutile TiO2

We perform first-principles calculations of the quasiparticle defect states, charge transition levels, and formation energies of oxygen vacancies in rutile titanium dioxide. The calculations are done within the recently developed combined DFT + GW formalism, including the necessary electrostatic corrections for the supercells with charged defects. We find the oxygen vacancy to be a negative U defect, where U is the defect electron addition energy. For Fermi level values below similar to 2.8 eV (relative to the valence-band maximum), we find the +2 charge state of the vacancy to be the most stable, while above 2.8 eV we find that the neutral charge state is the most stable.

Achieving universal rural energy access in india: A low carbon pathway

India's energy challenges are three pronged: presence of majority energy poor lacking access to modern energy; need for expanding energy system to bridge this access gap as well as to meet the requirements of fast-growing economy; and the desire to partner with global economies in mitigating the threat of climate change. The presence of 364 million people without access to electricity and 726 million relying on biomass for cooking out of a total rural population of 809 million indicate the seriousness of challenge. In this paper, we discuss an innovative approach to address this challenge, which intends to take advantage of recent global developments and untapped capabilities possessed by India. Intention is to use climate change mitigation imperative as a stimulus and adopt a public-private-partnership-driven ‘business model' with innovative institutional, regulatory, financing, and delivery mechanisms. Some of the innovations are: creation of rural energy access authorities within the government system as leadership institutions; establishment of energy access funds to enable transitions from the regime of "investment/fuel subsidies" to "incentive-linked" delivery of energy services; integration of business principles to facilitate affordable and equitable energy sales and carbon trade; and treatment of entrepreneurs as implementation targets. This proposal targets 100% access to modern energy carriers by 2030 through a judicious mix of conventional and biomass energy systems with an investment of US$35 billion over 20 years. The estimated annual cost of universal energy access is about US$9 billion for a GHG mitigation potential of 213Tg CO2e at an abatement cost of US$41/tCO2e. It is a win-win situation for all stakeholders. Households benefit from modern energy carriers at affordable cost; entrepreneurs run profitable energy enterprises; carbon markets have access to CERs; the government has the satisfaction of securing energy access to rural people; and globally, there is a benefit of climate change mitigation.

First-Principles Study of Structure, Vibrational, and Elastic Properties of Stoichiometric and Calcium-Deficient Hydroxyapatite

Hydroxyapatite (HAp), a primary constituent of human bone, is usually nonstoichiometric with varying Ca/P molar ratios, with the well-known fact that Ca deficiency can cause marked reductions in its mechanical properties. To gain insights into the mechanism of this degradation, we employ first-principles calculations based on density functional theory and determine the effects of Ca deficiency on structure, vibrational, and elastic properties of HAp. Our simulation results confirm a considerable reduction in the elastic constants of HAp due to Ca deficiency, which was experimentally reported earlier. Stress-induced transformation of the Ca-deficient defected structure into a metastable state upon the application of stress could be a reason for this. Local structural stability of HAp and Ca-deficient HAp structures is assessed with full phonon dispersion studies. Further, specific signatures in the computed vibrational spectra for Ca deficiency in HAp can be utilized in experimental characterization of different types of defected HAp.

Microscopic description of the evolution of the local structure and an evaluation of the chemical pressure concept in a solid solution

Extended x-ray absorption fine-structure studies have been performed at the Zn K and Cd K edges for a series of solid solutions of wurtzite Zn1-xCdxS samples with x = 0.0, 0.1, 0.25, 0.5, 0.75, and 1.0, where the lattice parameter as a function of x evolves according to the well-known Vegard's law. In conjunction with extensive, large-scale first-principles electronic structure calculations with full geometry optimizations, these results establish that the percentage variation in the nearest-neighbor bond distances are lower by nearly an order of magnitude compared to what would be expected on the basis of lattice parameter variation, seriously undermining the chemical pressure concept. With experimental results that allow us to probe up to the third coordination shell distances, we provide a direct description of how the local structure, apparently inconsistent with the global structure, evolves very rapidly with interatomic distances to become consistent with it. We show that the basic features of this structural evolution with the composition can be visualized with nearly invariant Zn-S-4 and Cd-S-4 tetrahedral units retaining their structural integrity, while the tilts between these tetrahedral building blocks change with composition to conform to the changing lattice parameters according to the Vegard's law within a relatively short length scale. These results underline the limits of applicability of the chemical pressure concept that has been a favored tool of experimentalists to control physical properties of a large variety of condensed matter systems.

Ontology analysis of global gene expression differences of human bone marrow stromal cells cultured on 3D scaffolds or 2D films

Differences in gene expression of human bone marrow stromal cells (hBMSCs) during culture in three-dimensional (3D) nanofiber scaffolds or on two-dimensional (2D) films were investigated via pathway analysis of microarray mRNA expression profiles. Previous work has shown that hBMSC culture in nanofiber scaffolds can induce osteogenic differentiation in the absence of osteogenic supplements (OS). Analysis using ontology databases revealed that nanofibers and OS regulated similar pathways and that both were enriched for TGF-beta and cell-adhesion/ECM-receptor pathways. The most notable difference between the two was that nanofibers had stronger enrichment for cell-adhesion/ECM-receptor pathways. Comparison of nanofibers scaffolds with flat films yielded stronger differences in gene expression than comparison of nanofibers made from different polymers, suggesting that substrate structure had stronger effects on cell function than substrate polymer composition. These results demonstrate that physical (nanofibers) and biochemical (OS) signals regulate similar ontological pathways, suggesting that these cues use similar molecular mechanisms to control hBMSC differentiation. Published by Elsevier Ltd.

Ranking of global climate models for India using multicriterion analysis

Eleven GCMs (BCCR-BCCM2.0, INGV-ECHAM4, GFDL2.0, GFDL2.1, GISS, IPSL-CM4, MIROC3, MRI-CGCM2, NCAR-PCMI, UKMO-HADCM3 and UKMO-HADGEM1) were evaluated for India (covering 73 grid points of 2.5 degrees x 2.5 degrees) for the climate variable `precipitation rate' using 5 performance indicators. Performance indicators used were the correlation coefficient, normalised root mean square error, absolute normalised mean bias error, average absolute relative error and skill score. We used a nested bias correction methodology to remove the systematic biases in GCM simulations. The Entropy method was employed to obtain weights of these 5 indicators. Ranks of the 11 GCMs were obtained through a multicriterion decision-making outranking method, PROMETHEE-2 (Preference Ranking Organisation Method of Enrichment Evaluation). An equal weight scenario (assigning 0.2 weight for each indicator) was also used to rank the GCMs. An effort was also made to rank GCMs for 4 river basins (Godavari, Krishna, Mahanadi and Cauvery) in peninsular India. The upper Malaprabha catchment in Karnataka, India, was chosen to demonstrate the Entropy and PROMETHEE-2 methods. The Spearman rank correlation coefficient was employed to assess the association between the ranking patterns. Our results suggest that the ensemble of GFDL2.0, MIROC3, BCCR-BCCM2.0, UKMO-HADCM3, MPIECHAM4 and UKMO-HADGEM1 is suitable for India. The methodology proposed can be extended to rank GCMs for any selected region.

Temperature-dependent stability of stacking faults in Al, Cu and Ni: first-principles analysis

We present comparative analysis of microscopic mechanisms relevant to plastic deformation of the face-centered cubic (FCC) metals Al, Cu, and Ni, through determination of the temperature-dependent free energies of intrinsic and unstable stacking faults along 1 (1) over bar 0] and 1 (2) over bar 1] on the (1 1 1) plane using first-principles density-functional-theory-based calculations. We show that vibrational contribution results in significant decrease in the free energy of barriers and intrinsic stacking faults (ISFs) of Al, Cu, and Ni with temperature, confirming an important role of thermal fluctuations in the stability of stacking faults (SFs) and deformation at elevated temperatures. In contrast to Al and Ni, the vibrational spectrum of the unstable stacking fault (USF1 (2) over bar 1]) in Cu reveals structural instabilities, indicating that the energy barrier (gamma(usf)) along the (1 1 1)1 (2) over bar 1] slip system in Cu, determined by typical first-principles calculations, is an overestimate, and its commonly used interpretation as the energy release rate needed for dislocation nucleation, as proposed by Rice (1992 J. Mech. Phys. Solids 40 239), should be taken with caution.

Elastic Properties Of Sulphur And Selenium Doped Ternary PbTe Alloys By First Principles

Lead telluride (PbTe) is an established thermoelectric material which can be alloyed with sulphur and selenium to further enhance the thermoelectric properties. Here, a first principles study of ternary alloys PbSxTe(1-x) and PbSexTe(1-x) (0 <= x <= 1) based on the Virtual Crystal Approximation (VCA) is presented for different ratios of the isoelectronic atoms in each series. Equilibrium lattice parameters and elastic constants have been calculated and compared with the reported data. Anisotropy parameter calculated from the stiffness constants showed a slight improvement in anisotropy of elastic properties of the alloys over undoped PbTe. Furthermore, the alloys satisfied the predicted stability criteria from the elastic constants, showing stable structures, which agreed with the previously reported experimental results.

A perturbed martingale approach to global optimization

A new global stochastic search, guided mainly through derivative-free directional information computable from the sample statistical moments of the design variables within a Monte Carlo setup, is proposed. The search is aided by imparting to the directional update term additional layers of random perturbations referred to as `coalescence' and `scrambling'. A selection step, constituting yet another avenue for random perturbation, completes the global search. The direction-driven nature of the search is manifest in the local extremization and coalescence components, which are posed as martingale problems that yield gain-like update terms upon discretization. As anticipated and numerically demonstrated, to a limited extent, against the problem of parameter recovery given the chaotic response histories of a couple of nonlinear oscillators, the proposed method appears to offer a more rational, more accurate and faster alternative to most available evolutionary schemes, prominently the particle swarm optimization. (C) 2014 Elsevier B.V. All rights reserved.

First principles study of metal contacts to monolayer black phosphorous

Atomically thin layered black phosphorous (BP) has recently appeared as an alternative to the transitional metal dichalcogenides for future channel material in a metal-oxide-semiconductor transistor due to its lower carrier effective mass. Investigation of the electronic property of source/drain contact involving metal and two-dimensional material is essential as it impacts the transistor performance. In this paper, we perform a systematic and rigorous study to evaluate the Ohmic nature of the side-contact formed by the monolayer BP (mBP) and metals (gold, titanium, and palladium), which are commonly used in experiments. Employing the Density Functional Theory, we analyse the potential barrier, charge transfer and atomic orbital overlap at the metal-mBP interface in an optimized structure to understand how efficiently carriers could be injected from metal contact to the mBP channel. Our analysis shows that gold forms a Schottky contact with a higher tunnel barrier at the interface in comparison to the titanium and palladium. mBP contact with palladium is found to be purely Ohmic, where as titanium contact demonstrates an intermediate behaviour. (C) 2014 AIP Publishing LLC.

ELLIPSE FITTING USING FINITE RATE OF INNOVATION PRINCIPLES

We address the problem of parameter estimation of an ellipse from a limited number of samples. We develop a new approach for solving the ellipse fitting problem by showing that the x and y coordinate functions of an ellipse are finite-rate-of-innovation (FRI) signals. Uniform samples of x and y coordinate functions of the ellipse are modeled as a sum of weighted complex exponentials, for which we propose an efficient annihilating filter technique to estimate the ellipse parameters from the samples. The FRI framework allows for estimating the ellipse parameters reliably from partial or incomplete measurements even in the presence of noise. The efficiency and robustness of the proposed method is compared with state-of-art direct method. The experimental results show that the estimated parameters have lesser bias compared with the direct method and the estimation error is reduced by 5-10 dB relative to the direct method.

The effect of gamma-gamma ` interface on the tensile and shear strengths of nickel-based superalloys: A first-principles study

First-principles density functional theory has been used to evaluate the shear and cleavage strength in terms of Griffith work and generalized stacking fault energy (GSF) of (001) plane for gamma, gamma' and gamma-gamma' system as a function of distance from the gamma/gamma' interface. Calculation of Griffith work suggests higher cleavage energy for bulk gamma as compared to gamma' while the GSF calculation suggests higher shear strength for bulk gamma' as compared to gamma. It has been found that the shear strength of the cubic plane of the gamma/gamma' interface is marginally lower than those of bulk gamma and gamma' phases. (C) 2014 Elsevier B.V. All rights reserved.

An overview of recent advances in structural bioinformatics of protein-protein interactions and a guide to their principles

Rich data bearing on the structural and evolutionary principles of protein protein interactions are paving the way to a better understanding of the regulation of function in the cell. This is particularly the case when these interactions are considered in the framework of key pathways. Knowledge of the interactions may provide insights into the mechanisms of crucial `driver' mutations in oncogenesis. They also provide the foundation toward the design of protein protein interfaces and inhibitors that can abrogate their formation or enhance them. The main features to learn from known 3-D structures of protein protein complexes and the extensive literature which analyzes them computationally and experimentally include the interaction details which permit undertaking structure-based drug discovery, the evolution of complexes and their interactions, the consequences of alterations such as post-translational modifications, ligand binding, disease causing mutations, host pathogen interactions, oligomerization, aggregation and the roles of disorder, dynamics, allostery and more to the protein and the cell. This review highlights some of the recent advances in these areas, including design, inhibition and prediction of protein protein complexes. The field is broad, and much work has been carried out in these areas, making it challenging to cover it in its entirety. Much of this is due to the fast increase in the number of molecules whose structures have been determined experimentally and the vast increase in computational power. Here we provide a concise overview. (C) 2014 Elsevier Ltd. All rights reserved.