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.

On strong centerpoints

Let P be a set of n points in R-d and F be a family of geometric objects. We call a point x is an element of P a strong centerpoint of P w.r.t..F if x is contained in all F is an element of F that contains more than cn points of P, where c is a fixed constant. A strong centerpoint does not exist even when F is the family of halfspaces in the plane. We prove the existence of strong centerpoints with exact constants for convex polytopes defined by a fixed set of orientations. We also prove the existence of strong centerpoints for abstract set systems with bounded intersection. (C) 2014 Elsevier B.V. All rights reserved.

On the strain rate sensitivity of plastic flow in metallic glasses

The nanoindentation technique was employed to examine the strain rate sensitivity, m, and its dependence on the structural state of a Zr-based bulk metallic glass (BMG). The free volume content in the BMG was varied by examining samples in the as-cast (AC), shot-peened (SP), and structurally relaxed (SR) states. Hardness values measured at different loading rates and over a temperature range of 300-423 K as well as the strain-rate jump tests conducted in the quasi-static regime at room temperature, show that m is always negative. All the load-displacement (P-h) curves in this temperature regime exhibit serrated load-displacement responses, indicating that the shear band mediated inhomogeneous plastic flow governs deformation. Such localization of flow and associated softening is the raison d'etre for the negative m. Significant levels of pile-up around the indents were also noted. The order in the average values of hardness, pile-up heights, and the displacement bursts on the P-h curves was always such that SR > AC > SP, which is also the order of increasing free volume content. These observations were utilized to discuss the reasons for the negative strain rate sensitivity, and its dependence on the structural state of metallic glasses. It is suggested that the positive values of m reported in the literature for them are possibly experimental artefacts that arise due to large pile ups around the indents which lead to erroneous estimation in hardness values. (C) 2014 Elsevier B.V. All rights reserved.

Studies on the effects of varying secondary gas properties in a low entrainment ratio supersonic ejector

A dilution cum purge ejector for application in fuel cells represents a domain of ejector operation involving low entrainment ratio with differing secondary and primary gas; which is hardly investigated and a cohesive design framework is not readily available. We comprehensively study a constant area ejector using analytical, experimental and numerical tools at low entrainment ratio (0.004-0.065) with Air, Helium and Argon as secondary gas while the primary gas is Air. For the first time, limits of operating parameters used in control volume method to design the ejector are found to be highly dependent on the secondary molecular weight. The entrainment ratio in the ejector (low for Helium and high for Argon) is affected by the molecular weight and the static pressure within the ejector (low for Air and high for Argon & Helium) by the gamma of the secondary gas. Sufficient suction pressure (0.3-0.55 bar) is generated by the ejector thereby preventing any backflow of secondary gas at all primary stagnation pressures (1.5, 2.2 and 3.1 bar). Numerical results agree well with experimental results. The ejector is shown to completely dilute and purge the secondary flow, meeting all key design requirements. (C) 2014 Elsevier Ltd. All rights reserved.

Kaiser effect observation in reinforced concrete structures and its use for damage assessment

Reinforced concrete (RC) beams of span 3 m were tested under incremental cyclic load at different loading rates and simultaneously during the fracture process in the RC beams acoustic emissions (AE) were recorded. An attempt has been made to study the Kaiser effect as a measure of damage in RC beams. It was observed that RC beams made with high strength concrete under incremental cyclic loading showed an obvious Kaiser effect before the failure load. The results may be useful to study the damage in concrete structures and provide a reference for the application of Kaiser effect in engineering practice. (C) 2014 Politechnika Wroclawska. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Long-term effects of Macroternies termites, herbivores and annual early fire on woody undergrowth community in Sudanian woodland, Burkina Faso

Termites, herbivores and fire are recognized as major guilds that structure woody plant communities in African savanna and woodland ecosystems. An understanding of their interaction is crucial to design appropriate management regimes. The aim of this study was to evaluate the long-term impacts of herbivore, fire and termite activities on regeneration of trees. Permanent experimental quadrats were established in 1992 in the Sudanian woodland of Burkina Faso subjected to grazing by livestock and annual early fire and the control. Within the treatment quadrats, an inventory of the woody undergrowth community was conducted on termitaria occupied by Macrotermes subhyalinus, extended termitosphere (within 5 m radius from the mound base) and adjacent area (beyond 5 m from the mound base). Hierarchical analysis was performed to determine significant differences in species richness, abundance and diversity indices among vegetation patches within fire and herbivory treatments. Grazed quadrats had significantly (P < 0.001) more species and stem density of woody undergrowth than non-grazed quadrats but maintained similar level of species richness and stem density of woody undergrowth on termitaria. There were not significant differences (P>0.05) in species richness and stem density between burnt and unburnt quadrats. Termitaria supported a highly diverse woody undergrowth with higher stem density than either the extended termitosphere or rest of quadrats. The density of woody undergrowth was significantly related with mature trees of selected species on termitaria (R-2 = 0.593; P<0.001) than that on the extended termitosphere (R-2 = 0.333; P<0.001) and adjacent area (R-2 = 0.197; P<0.001). It can be concluded that termites facilitate the regeneration of woody species while grazing and annual early fire play a minor role in the regeneration of woody species. The current policy that prohibits grazing should be revised to accommodate the interests of livestock herders. (C) 2014 Elsevier GmbH. All rights reserved.

Challenges in the quantification and interpretation of spike-LFP relationships

Brain signals often show fluctuations in particular frequency bands, which are highly conserved across species and are associated with specific behavioural states. Such rhythmic patterns can be captured in the local field potential (LFP), which is obtained by low-pass filtering the extracellular signal recorded from microelectrodes. However, LFP also captures other neural processes that are associated with spikes, such as synaptic events preceding a spike, low-frequency component of the action potential (spike bleed-through'') and spike afterhyperpolarization, which pose difficulties in the estimation of the amplitude and phase of the rhythm with respect to spikes. Here we discuss these issues and different techniques that have been used to dissociate the rhythm from other neural events in the LFP.

Markov chain splitting methods in structural reliability integral estimation

Monte Carlo simulation methods involving splitting of Markov chains have been used in evaluation of multi-fold integrals in different application areas. We examine in this paper the performance of these methods in the context of evaluation of reliability integrals from the point of view of characterizing the sampling fluctuations. The methods discussed include the Au-Beck subset simulation, Holmes-Diaconis-Ross method, and generalized splitting algorithm. A few improvisations based on first order reliability method are suggested to select algorithmic parameters of the latter two methods. The bias and sampling variance of the alternative estimators are discussed. Also, an approximation to the sampling distribution of some of these estimators is obtained. Illustrative examples involving component and series system reliability analyses are presented with a view to bring out the relative merits of alternative methods. (C) 2015 Elsevier Ltd. All rights reserved.

Economic tradeoffs in mitigation, due to different atmospheric lifetimes of CO2 and black carbon

Tradeoffs are examined between mitigating black carbon (BC) and carbon dioxide (CO2) for limiting peak global mean warming, using the following set of methods. A two-box climate model is used to simulate temperatures of the atmosphere and ocean for different rates of mitigation. Mitigation rates for BC and CO2 are characterized by respective timescales for e-folding reduction in emissions intensity of gross global product. There are respective emissions models that force the box model. Lastly there is a simple economics model, with cost of mitigation varying inversely with emission intensity. Constant mitigation timescale corresponds to mitigation at a constant annual rate, for example an e-folding timescale of 40 years corresponds to 2.5% reduction each year. Discounted present cost depends only on respective mitigation timescale and respective mitigation cost at present levels of emission intensity. Least-cost mitigation is posed as choosing respective e-folding timescales, to minimize total mitigation cost under a temperature constraint (e.g. within 2 degrees C above preindustrial). Peak warming is more sensitive to mitigation timescale for CO2 than for BC. Therefore rapid mitigation of CO2 emission intensity is essential to limiting peak warming, but simultaneous mitigation of BC can reduce total mitigation expenditure. (c) 2015 Elsevier B.V. All rights reserved.

A zero charge-pump mismatch current tracking loop for reference spur reduction in PLLs

The charge-pump (CP) mismatch current is a dominant source of static phase error and reference spur in the nano-meter CMOS PLL implementations due to its worsened channel length modulation effect. This paper presents a charge-pump (CP) mismatch current reduction technique utilizing an adaptive body bias tuning of CP transistors and a zero CP mismatch current tracking PLL architecture for reference spur suppression. A chip prototype of the proposed circuit was implemented in 0.13 mu m CMOS technology. The frequency synthesizer consumes 8.2 mA current from a 13 V supply voltage and achieves a phase noise of -96.01 dBc/Hz @ 1 MHz offset from a 2.4 GHz RF carrier. The charge-pump measurements using the proposed calibration technique exhibited a mismatch current of less than 0.3 mu A (0.55%) over the VCO control voltage range of 0.3-1.0 V. The closed loop measurements show a minimized static phase error of within +/- 70 ps and a similar or equal to 9 dB reduction in reference spur level across the PLL output frequency range 2.4-2.5 GHz. The presented CP calibration technique compensates for the DC current mismatch and the mismatch due to channel length modulation effect and therefore improves the performance of CP-PLLs in nano-meter CMOS implementations. (C) 2015 Elsevier Ltd. All rights reserved.

The crystal structure of a lectin from Butea monosperma: Insight into its glycosylation and binding of ligands

Crystal structure of a lectin purified from Butea monosperma seeds was determined by Molecular Replacement method. Its primary structure was determined by Tandem Mass Spectroscopy and electron density maps from X-ray diffraction data. Its quaternary structure was tetrameric, formed of two monomers, alpha and beta, beta appearing as truncated alpha. The occurrence of two tetramers in the asymmetric unit of the crystal might be a consequence of asymmetric contacts due to difference in glycosylation and variable loops structures, to form an `octamer-structure'. The crystal structure showed binding pockets for gamma Abu, having a proposed role in plant defense, at the interface of canonical dimer-partners. Hemagglutination studies, enzyme kinetics, isothermal titration calorimetry and molecular dynamics showed that the lectin is specific to N-acetyl D-galactosamine, galactose and lactose in decreasing order, and alpha-amylase inhibitor. (C) 2014 Elsevier B.V. All rights reserved.

A comparison of the fine-scale structure of the diurnal cycle of tropical rain and lightning

In this study, the fine-scale structure of the diurnal variability of ground-based lightning is systematically compared with satellite-based rain. At the outset, it is shown that tropical variability of lightning exhibits a prominent diurnal mode, much like rain. A comparison of the geographical distribution of the timing of the diurnal maximum shows that there is very good agreement between the two observables over continental and coastal regions throughout the tropics. Following this global tropical comparison, we focus on two regions, Borneo and equatorial South America, both of which show the interplay between oceanward and landward propagations of the phase of the diurnal maximum. Over Borneo, both rain and lightning clearly show a climatological cycle of ``breathing in'' (afternoon to early morning) and ``breathing out'' (morning to early afternoon). Over the equatorial east coast of South America, landward propagation is noticed in rain and lightning from early afternoon to early morning. Along the Pacific coast of South America, both rain and lightning show oceanward propagation. Though qualitatively consistent, over both regions the propagation is seen to extend further in rainfall. Additionally, given that lightning highlights vigorous convection, the timing of its diurnal maximum often precedes that of rainfall in the convective life cycle. (C) 2015 Elsevier B.V. All rights reserved.

DETERMINISTIC ALGORITHMS FOR MATCHING AND PACKING PROBLEMS BASED ON REPRESENTATIVE SETS

In this work, we study the well-known r-DIMENSIONAL k-MATCHING ((r, k)-DM), and r-SET k-PACKING ((r, k)-SP) problems. Given a universe U := U-1 ... U-r and an r-uniform family F subset of U-1 x ... x U-r, the (r, k)-DM problem asks if F admits a collection of k mutually disjoint sets. Given a universe U and an r-uniform family F subset of 2(U), the (r, k)-SP problem asks if F admits a collection of k mutually disjoint sets. We employ techniques based on dynamic programming and representative families. This leads to a deterministic algorithm with running time O(2.851((r-1)k) .vertical bar F vertical bar. n log(2)n . logW) for the weighted version of (r, k)-DM, where W is the maximum weight in the input, and a deterministic algorithm with running time O(2.851((r-0.5501)k).vertical bar F vertical bar.n log(2) n . logW) for the weighted version of (r, k)-SP. Thus, we significantly improve the previous best known deterministic running times for (r, k)-DM and (r, k)-SP and the previous best known running times for their weighted versions. We rely on structural properties of (r, k)-DM and (r, k)-SP to develop algorithms that are faster than those that can be obtained by a standard use of representative sets. Incorporating the principles of iterative expansion, we obtain a better algorithm for (3, k)-DM, running in time O(2.004(3k).vertical bar F vertical bar . n log(2)n). We believe that this algorithm demonstrates an interesting application of representative families in conjunction with more traditional techniques. Furthermore, we present kernels of size O(e(r)r(k-1)(r) logW) for the weighted versions of (r, k)-DM and (r, k)-SP, improving the previous best known kernels of size O(r!r(k-1)(r) logW) for these problems.

Effect of Ga content in Cu(Ga) on the growth of V3Ga following bronze technique

Diffusion controlled growth rate of V3Ga in the Cu(Ga)/V system changes dramatically because of a small change in Ga content in Cu(Ga). One atomic percent increase from 15 to 16 leads to more than double the product phase layer thickness and a decrease in activation energy from 255 to 142 kJ/mol. Kirkendall marker experiment indicates that V3Ga grows because of diffusion of Ga. Role of different factors influencing the diffusion rate of Ga and high growth rate of V3Ga are discussed. (C) 2015 Elsevier Ltd. All rights reserved.

Reply to Discussion on ``Bearing capacity of circular footings over rock mass by using axisymmetric quasi lower bound finite element limit analysis'' Comput. Geotech. 70 (2015) 138-149]

A discussion has been provided for the comments raised by the discusser (Clausen, 2015)1] on the article recently published by the authors (Chakraborty and Kumar, 2015). The effect of exponent alpha for values of GSI approximately smaller than 30 becomes more critical. On the other hand, for greater values of GSI, the results obtained by the authors earlier remain primarily independent of alpha and can be easily used. (C) 2015 Elsevier Ltd. All rights reserved.