Comparison of tertiary structures of proteins in protein-protein complexes with unbound forms suggests prevalence of allostery in signalling proteins

Abstract: Background: Most signalling and regulatory proteins participate in transient protein-protein interactions during biological processes. They usually serve as key regulators of various cellular processes and are often stable in both protein-bound and unbound forms. Availability of high-resolution structures of their unbound and bound forms provides an opportunity to understand the molecular mechanisms involved. In this work, we have addressed the question "What is the nature, extent, location and functional significance of structural changes which are associated with formation of protein-protein complexes?" Results: A database of 76 non-redundant sets of high resolution 3-D structures of protein-protein complexes, representing diverse functions, and corresponding unbound forms, has been used in this analysis. Structural changes associated with protein-protein complexation have been investigated using structural measures and Protein Blocks description. Our study highlights that significant structural rearrangement occurs on binding at the interface as well as at regions away from the interface to form a highly specific, stable and functional complex. Notably, predominantly unaltered interfaces interact mainly with interfaces undergoing substantial structural alterations, revealing the presence of at least one structural regulatory component in every complex. Interestingly, about one-half of the number of complexes, comprising largely of signalling proteins, show substantial localized structural change at surfaces away from the interface. Normal mode analysis and available information on functions on some of these complexes suggests that many of these changes are allosteric. This change is largely manifest in the proteins whose interfaces are altered upon binding, implicating structural change as the possible trigger of allosteric effect. Although large-scale studies of allostery induced by small-molecule effectors are available in literature, this is, to our knowledge, the first study indicating the prevalence of allostery induced by protein effectors. Conclusions: The enrichment of allosteric sites in signalling proteins, whose mutations commonly lead to diseases such as cancer, provides support for the usage of allosteric modulators in combating these diseases.

Thermodynamics of Congruent Oxidation

Congruent oxidation occurs when an alloy oxidizes at constant oxygen chemical potential and temperature to an oxide in which the ratio of metallic components is the same as in the alloy. In alloys that undergo congruent oxidation concentration gradients near the surface are minimized. In this work thermodynamic conditions for congruent oxidation of binary and ternary alloys are formulated using the regular solution model to describe thermodynamic mixing properties. The conditions under which congruent oxidation can occur are identified. Congruent oxidation of a binary alloy X-Y will occur only if difference in oxygen potential for the oxidation of the two pure metals is less than twice the difference in regular solution parameters for the oxide and alloy phases (Omega(O)-Omega(A)). In the case of ternary alloys, congruency requirements for both two-phase and three-phase equilibria are discussed. Since the conditions for congruent oxidation of ternary alloy X-Y-Z depends on many parameters, the effect of systematic variation of the binary sets of regular solution parameters on the congruent composition is explored by numerical solution of the governing equations.

Correlations of vaporization performance of conventional and biofuel sprays in a crossflow heated chamber

Pre-vaporization and pre-mixing are the two main features of LPP type of combustor that operate on liquid fuels. The pre-vaporization length scale is one of its most important design parameters. In this study, the goal is to put forward a simulation based correlation for fuel vaporization performance as a function of dimensionless parameters for crossflow type of injections. Two types of fuels are studied here: jet-A and one of its potential biofuel substitutes, RME. Different sets of spray simulations are considered for crossflow type of injections. Correlations are provided for both jet-A and RME's vaporization performance as a function of non-dimensional inlet air temperature, fuel/air momentum flux ratio and normalized spray traverse distance. (C) 2012 Elsevier Ltd. All rights reserved.

Some questions on integral geometry on noncompact symmetric spaces of higher rank

Let be a noncompact symmetric space of higher rank. We consider two types of averages of functions: one, over level sets of the heat kernel on and the other, over geodesic spheres. We prove injectivity results for functions in which extend the results in Pati and Sitaram (Sankya Ser A 62:419-424, 2000).

Investigation of the origin of glassiness in La0.5Sr0.5CoO3

A comprehensive magnetic study has been carried out on the two sets of La0.5Sr0.5CoO3 samples with a view to understand the origin of low temperature glassiness in the ferromagnetic state. The samples prepared by the conventional solid-state synthesis method show a low temperature shoulder in both dc magnetization as well as in the ac susceptibility measurements, which exhibit characteristics of glassiness such as the frequency dependence and memory effect. These observations suggest the existence of a distinct low temperature cluster-glass like phase within dominant ferromagnetic phase. But, once the same sample is properly homogenized by repeated grinding and annealing process, the low temperature glassy phase disappears, and it shows a pure ferromagnetic behavior. Our comparative study clearly reveals that the reentrant spin-glass like nature is not intrinsic to La0.5Sr0.5CoO3 system, in fact this is an outcome of the compositional inhomogeneity.

Tradeoff of average power and average delay for a point-to-point link with fading

We consider a discrete time system with packets arriving randomly at rate lambda per slot to a fading point-to-point link, for which the transmitter can control the number of packets served in a slot by varying the transmit power. We provide an asymptotic characterization of the minimum average delay of the packets, when average transmitter power is a small positive quantity V more than the minimum average power required for queue stability. We show that the minimum average delay will grow either as log (1/V) or 1/V when V down arrow 0, for certain sets of values of lambda. These sets are determined by the distribution of fading gain, the maximum number of packets which can be transmitted in a slot, and the assumed transmit power function, as a function of the fading gain and the number of packets transmitted. We identify a case where the above behaviour of the tradeoff differs from that obtained from a previously considered model, in which the random queue length process is assumed to evolve on the non-negative real line.

Organogels from Dimeric Bile Acid Esters: In Situ Formation of Gold Nanoparticles

A new class of steroid dimers (bile acid derivatives) linked through ester functionalities were synthesized, which gelled various aromatic solvents. The organogels formed by the three dimeric ester molecules showed birefringent textures and fibrous nature by polarizing optical microscopy and scanning electron microscopy, respectively. A detailed rheological study was performed to estimate the mechanical strengths of two sets of organogels. In these systems, the storage modulus varied in the range of 0.8-3.5 X 10(4) at 1% w/v of the organogelators. The exponents of scaling of the storage modulus and yield stress of the two systems agreed well with those expected for viscoelastic soft colloidal gels with fibrillar flocs. The nanofibers in the organogel were utilized to engineer gold nanoparticles of different sizes and shapes and generate new gel-nanoparticle hybrid materials.

Continuous beam of laser-cooled Yb atoms

We demonstrate the launching of laser-cooled Yb atoms in a continuous atomic beam. The continuous cold beam has significant advantages over the more-common pulsed fountain, which was also demonstrated by us recently. The cold beam is formed in the following steps: i) atoms from a thermal beam are first Zeeman-slowed to a small final velocity; ii) the slowed atoms are captured in a two-dimensional magneto-optic trap (2D-MOT); and iii) atoms are launched continuously in the vertical direction using two sets of moving-molasses beams, inclined at +/- 15 degrees to the vertical. The cooling transition used is the strongly allowed S-1(0) -> P-1(1) transition at 399 nm. We capture about 7x10(6) atoms in the 2D-MOT, and then launch them with a vertical velocity of 13m/s at a longitudinal temperature of 125(6) mK. Copyright (C) EPLA, 2013

Ferromagnetic Resonance Study on a Grid of Permalloy Nanowires

We report ferromagnetic resonance (FMR) study on a grid formed with permalloy nanowires to understand the spin wave dynamics. The presence of two sets of magnetic nanowires perpendicular to each other in the same device enables better control over spin waves. The grid was fabricated using e-beam lithography followed by DC-Magnetron sputtering and liftoff technique. It has dimensions of 800 +/- 10 and 400 +/- 10 nm as periods along X and Y directions with permalloy wires of width 145 +/- 10 nm. FMR studies were done at X-band (9.4 GHz) with the field sweep up to 1 Tesla. The in-plane angular variation of resonant fields shows that there are two well separated modes present, indicating two uniaxial anisotropy axes which are perpendicular to each other. The variation in the intensities in the FMR signal w.r.t. the grid angle is used to describe the spin wave confinement in different regions of the grid. We also explained the asymmetry in the magnetic properties caused by the geometrical property of the rectangular grid and the origin for the peak splitting for the modes occurring at higher resonant fields. Micromagnetic simulations based on OOMMF with two dimensional periodic boundary conditions (2D-PBC) are used to support our experimental findings.

Synthon modularity in Cocrystals of 4-Bromobenzamide with n-Alkanedicarboxylic acids: type I and type ll Halogen center dot center dot center dot Halogen interactions

A Cambridge Structural Database (CSD) analysis on halogen center dot center dot center dot halogen contacts (X...X) in organic crystals has been carried out to review the classification criteria for type I, type II, and quasi type I/II halogen interactions. Trends observed in previous CSD analyses of the phenomenon are reinforced in the present study. The manner in which these interactions are manifested in cocrystals of 4-bromobenzamide and dicarboxylic acid is examined. The design strategy for these cocrystals uses synthon theory and follows from an understanding of the crystal structures of gamma-hydroquinone and a previously studied set of 4-hydroxybenzamide dicarboxylic acid cocrystals, making use of Br/OH isostructurality. All cocrystals are obtained by clean insertion of dicarboxylic acids between 4-bromobenzamide molecules. The strategy is deliberate and the prediction of synthons done well in advance, as evidenced from the robustness of the acid-amide heterosynthons in all nine crystal structures, with no aberrant structures in the crystallization experiments. Formation of the acid-amide synthon in these cocrystals is identified with IR spectroscopy. The packing in these cocrystals can be distinguished in terms of whether the Br...Br interactions are type I or II. Eight sets of dimorphs were retrieved from the CSD, wherein the basis of the polymorphism is that one crystal has a type I Br...Br interaction, while the other has a type II interaction.

Vorticity moments in four numerical simulations of the 3D Navier-Stokes equations

The issue of intermittency in numerical solutions of the 3D Navier-Stokes equations on a periodic box 0, L](3) is addressed through four sets of numerical simulations that calculate a new set of variables defined by D-m(t) = (pi(-1)(0) Omega(m))(alpha m) for 1 <= m <= infinity where alpha(m) = 2m/(4m - 3) and Omega(m)(t)](2m) = L-3 integral(v) vertical bar omega vertical bar(2m) dV with pi(0) = vL(-2). All four simulations unexpectedly show that the D-m are ordered for m = 1,..., 9 such that Dm+1 < D-m. Moreover, the D-m squeeze together such that Dm+1/D-m NE arrow 1 as m increases. The values of D-1 lie far above the values of the rest of the D-m, giving rise to a suggestion that a depletion of nonlinearity is occurring which could be the cause of Navier-Stokes regularity. The first simulation is of very anisotropic decaying turbulence; the second and third are of decaying isotropic turbulence from random initial conditions and forced isotropic turbulence at fixed Grashof number respectively; the fourth is of very-high-Reynolds-number forced, stationary, isotropic turbulence at up to resolutions of 4096(3).

Vibrational spectra of fluorene, 1-methylfluorene and 1,8-dimethylfluorene

In this paper, we report the gas phase infrared spectra of fluorene and its methylated derivatives using a heated multipass cell and argon as a carrier gas. The observed spectra in the 4000-400 cm(-1) range have been fitted using the modified scaled quantum mechanical force field (SQMFF) calculation with the 6-311G** basis. The advantage of using the modified SQMFF method is that it scales the force constants to find the best fit to the observed spectral lines by minimizing the fitting error. In this way we are able to assign all the observed fundamental bands in the spectra. With consecutive methyl substitutions two sets of bands are found to shift in a systematic way. The set of four aromatic C-H stretching vibrations around 3000 cm(-1) shifts toward lower frequencies while the single most intense aromatic C-H out-of-plane bending mode around 750 cm(-1) shifts toward higher frequencies. The reason for shifting of aromatic C-H stretching frequency toward lower wave numbers with gradual methyl substitution has been attributed to the lengthening of the C-H bonds due to the +I effect of the methyl groups to the ring current as revealed from the calculations. While the unexpected shifting of the aromatic C-H out-of-plane bend toward higher wave numbers with increasing methyl substitution is ascribed to the lowering of the number of adjacent aromatic C-H bonds on the plane of the benzene ring with gradual methyl substitutions. (C) 2013 Elsevier B.V. All rights reserved.

Experimental analysis of composite single-lap joints using digital image correlation and comparison with theoretical models

The demand for energy efficient, low weight structures has boosted the use of composite structures assembled using increased quantities of structural adhesives. Bonded structures may be subjected to severe working environments such as high temperature and moisture due to which the adhesive gets degraded over a period of time. This reduces the strength of a joint and leads to premature failure. Measurement of strains in the adhesive bondline at any point of time during service may be beneficial as an assessment can be made on the integrity of a joint and necessary preventive actions may be taken before failure. This paper presents an experimental approach of measuring peel and shear strains in the adhesive bondline of composite single-lap joints using digital image correlation. Different sets of composite adhesive joints with varied bond quality were prepared and subjected to tensile load during which digital images were taken and processed using digital image correlation software. The measured peel strain at the joint edge showed a rapid increase with the initiation of a crack till failure of the joint. The measured strains were used to compute the corresponding stresses assuming a plane strain condition and the results were compared with stresses predicted using theoretical models, namely linear and nonlinear adhesive beam models. A similar trend in stress distribution was observed. Further comparison of peel and shear strains also exhibited similar trend for both healthy and degraded joints. Maximum peel stress failure criterion was used to predict the failure load of a composite adhesive joint and a comparison was made between predicted and actual failure loads. The predicted failure loads from theoretical models were found to be higher than the actual failure load for all the joints.

Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of ``how much'' information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on ``what'' is coded by primary afferents. Amongst the kinematic variables tested-position, velocity, and acceleration-primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80-90%. The final 10-20% were found to be due to non-linear coding by spike bursts.

ENDOR studies of hydrogen bonding of the AsO44- centre in x-ray irradiated KH2AsO4

We here report what we believe to be an important method for studying hydrogen bonding in systems containing a paramagnetic centre. The technique of electron-nuclear double resonance ( ENDOR) has been applied to study the hydrogen-bond network around the AsO44-. centre in X-ray irradiated KH2AsO4. ENDOR transitions from several sets of hydrogen nuclei surrounding the centre were observed at 4.2 degrees K and the spectra for two sets of neighbouring nuclei are identified. The angular dependences for these spectra are fitted with a spin-Hamiltonian to obtain the isotropic and anisotropic magnetic hyperfine constants. The results are discussed in terms of the available spectroscopic and crystallographic data on KH2AsO4 and the order-disorder model of ferroelectrictricity in this class of crystals.