Conformational Analysis of a 20-Membered Cyclic Peptide Disulfide from Conus virgo with a WPW Segment: Evidence for an Aromatic-Proline Sandwich

A novel peptide containing a single disulfide bond, CIWPWC (Vi804), has been isolated and characterised from the venom of the marine cone snail, Conus virgo. A precursor polypeptide sequence derived from complementary DNA, corresponding to the M-superfamily conotoxins, has been identified. The identity of the synthetic and natural peptide sequence has been established. A detailed analysis of the conformation in solution is reported for Vi804 and a synthetic analogue, (CIWPWC)-W-D ((D)W3-Vi804), in order to establish the structure of the novel WPW motif, which occurs in the context of a 20-membered macrocyclic disulfide. Vi804 exists exclusively in the cis W3P4 conformer in water and methanol, whereas (D)W3-Vi804 occurs exclusively as the trans conformer. NMR spectra revealed a W3P4 typeVI turn in Vi804 and a typeII turn in the analogue peptide, (D)W3-Vi804. The extremely high-field chemical shifts of the proline ring protons, together with specific nuclear Overhauser effects, are used to establish a conformation in which the proline ring is sandwiched between the flanking Trp residues, which emphasises a stabilising role for the aromatic-proline interactions, mediated predominantly by dispersion forces.

Characterizing Frictional Contact Loading via Isochromatics

Isochromatic patterns in the vicinity of frictional contacts furnish vital clues for characterizing friction. Though friction effects are evident in a diametrally loaded circular disk, three-point loading provides better results towards highlighting friction. In this paper, a new method of characterizing friction at loading contacts using photoelastic isochromatics patterns is presented. Location of isotropic points (IPs) formed in three-point and four-point loadings of circular disk is used as a main tool to quantify the friction component using theoretical analysis. Bifurcation of isochromatic fringe loops near the distributed loads is explained by the presence of anti-symmetric Hertzian shear traction in addition to Hertzian normal traction. The classical solution by Flamant for point load at the edge of half plane is used to derive stresses in circular disk for all required loading configurations. A semicircualr ring under three-point loading is examined using photoelasticity to understand the isochromatics pattern theoretically by considering normal and shear traction components at loaded regions.

Asymptotic expansions for wavenumbers in orthotropic fluid-filled circular cylindrical shells for intermediate fluid loading

Coupled wavenumbers in infinite fluid-filled isotropic and orthotropic cylindrical shells are considered. Using the Donnell-Mushtari (DM) theory for thin shells, compact and elegant asymptotic expansions for the wavenumbers are found at an intermediate fluid loading for both the coupled rigid-duct modes (''fluid-originated'') and the coupled structural wavenumbers (''structure-originated modes'') over the entire frequency range where DM theory is valid. The coupled rigid-duct expansions are found to be valid for O(1) orthotropy and for all circumferential orders, whereas the coupled structural wavenumber expansions are valid for small orthotropy and for low circumferential orders. These two above results are then used to derive the expansions for a set of multiple complex roots that display a locking behavior at this intermediate fluid-loading. The expansions are matched with the numerical solutions of the coupled dispersion relation and the match is found to be good over most of the frequency range. (C) 2014 Acoustical Society of America.

Static shear strength and fatigue life of refill friction stir spot welded AA 6061-T6 sheets

This study was aimed at evaluating the static shear strength and fatigue properties of the newly developed refilled friction stir spot welded AA 6061-T6 joints. The keyhole, the process disadvantage of conventional friction stir spot welding, was refilled successfully, using an additional filler plate, with specially designed tools. Two different tool profiles, namely, convex and concave, were used for the refilling process. Sound and defect free joints were obtained by the refilling process. Joints refilled with convex tools showed better static shear strength than those with the concave ones. The variation of microhardness in different regions of the weld was analysed. Fatigue tests were conducted on the lap shear specimens at a stress ratio of R=0.1. The optical micrographs of the welds after fatigue failure in both the conventional and refilled processes were examined to study the fatigue crack propagation and failure modes.

Effect of adsorbate loading on selectivity during adsorption of C/C and C/C n-alkane binary mixtures in silicalite

Adsorption experiments of mixtures of long chain alkanes into silicalite under liquid phase conditions show selectivity inversion and azeotrope formation. These effects are due to the subtle interplay between the size of the adsorbed molecules and pore topology of the adsorbent. In this study, the selective uptake of lighter component during liquid phase adsorption of C/C and C/C n-alkane binary mixtures in the zeolite silicalite is understood through configurational bias grand-canonical Monte Carlo molecular simulation technique and a coarse-grained siting analysis. The simulations are conducted under conditions of low and intermediate levels of loading. The siting pattern of the adsorbates inside the zeolite pores explain the selectivity as seen in experiments.

Tonic current through GABAA receptors and hyperpolarization-activated cyclic nucleotide-gated channels modulate resonance properties of rat subicular pyramidal neurons

The subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. Using pharmacological agents, we show the involvement of alpha 5 beta gamma GABA(A) receptors in the picrotoxin-sensitive tonic current in subicular pyramidal neurons. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. We demonstrate that tonic GABAergic inhibition can actively modulate subthreshold properties, including resonance due to HCN channels, which can potentially alter the response dynamics of subicular pyramidal neurons in an oscillating neuronal network.

Backbone-modified amphiphilic cyclic di- and tetrasaccharides

Synthesis of amphiphilic, cyclic di- and tetrasaccharides, which incorporate a methylene moiety at the inter-glycosidic bond, is reported. The amphiphilic properties of the new cyclic tetrasaccharide host were identified through assessing the solubilities of guests in aqueous and in organic solvents. The glycosidic bond stability of the cyclic tetrasaccharide under aqueous acidic condition was also verified.

Orientation, Size, and Temperature Dependent Ductile Brittle Transition in NiAl Nanowire under Tensile Loading - A Molecular Dynamics Study

In the present paper, thermo-mechanical response of B2-NiAl nanowire along the < 100 >, < 110 >, and < 111 > orientations has been studied using molecular dynamics simulations. Nanowire with cross-sectional dimensions of similar to 20x20 angstrom(2), similar to 25x25 angstrom(2), and similar to 30x30 angstrom(2) and temperature range of 10 K-900 K has been considered. A Combined effect of size, orientation, and temperature on the stress-strain behavior under uniaxial tensile loading has been presented. It has been observed that < 111 > oriented NiAl nanowire that is energetically most stable gives highest yield stress which further reduces with < 110 > and < 100 > orientations. A remarkable ductile brittle transition (DBT) with an increase in temperature has also been reported for all the orientations considered in the present study. The DBT observed for the nanowire has also been compared with the reported DBT of bulk B2-NiAl obtained from experiments. Alternate technique has also been proposed to increase the toughness of a given material especially at lower temperature regions, i.e. below DBT.

beta gamma-fused turn structures in sugar amino acid (SAA) containing cyclic tetrapeptides with alpha 3 delta architecture

The current manuscript describes conformational analysis of 15-membered cyclic tetrapeptides (CTPs), with alpha 3 delta architecture, containing sugar amino acids (SAA) having variation in the stereocenter at C5 carbon. Conformational analyses of both the series, in protected and deprotected forms, were carried out in DMSO-d(6) using various NMR techniques, supported by restrained MD calculations. It was intriguing to notice that the alpha 3 delta macrocycles got stabilized by both 10-membered beta-turn as well as a seven-membered gamma-turn, fused within the same macrocycle. The presence of fused sub-structures within a 15-membered macrocycle is rare to see. Also, the stereocenter variation at C5 did not affect the fused turn structures and exhibited similar conformations in both the series. The design becomes highly advantageous as fused reverse turn structures are occurring in the cyclic structure with minimalistic size macrocycle and this can be applied to develop suitable pharmacophores in the drug development process. (C) 2014 Elsevier Ltd. All rights reserved.

Analysis of cracked and un-cracked semicircular rings under symmetric loading

Edge cracked specimens have been widely utilized for fracture testing. Edge cracked semicircular disk (ECSD) specimen has now been well characterized with regard to its form factor and weight function. This paper presents a modified semicircular ring version of this specimen to enhance the form factor in general while retaining other desirable features. The efficacy of the modified design is proved by combining theory of elasticity solutions with finite element results to arrive at the optimum design geometry. New insights emerging from this work are used to theoretically re-examine the arch-tension and the four-point bend specimens. (C) 2014 Elsevier Ltd. All rights reserved.

An experimental study on loading rate effect on acoustic emission based b-values related to reinforced concrete fracture

This article reports on analysis of fracture processes in reinforced concrete (RC) beams with acoustic emission (AE) technique. An emphasis was given to study the effect of loading rate on variation in AE based b-values with the development of cracks in RC structures. RC beams of length 3.2 m were tested under load control at a rate of 4 kN/s, 5 kN/s and 6 kN/s and the b-value analysis available in seismology was used to study the fracture process in RC structures. Moreover, the b-value is related to the strain in steel to assess the damage state. It is observed that when the loading rate is higher, quick cracking development lead to rapid fluctuations and drops in the b-values. Also it is observed that concrete behaves relatively more brittle at higher loading rates (or at higher strain rates). The average b-values are lower as a few but larger amplitudes of AE events occur in contrast to more number of low amplitude AE events occur at low loading rates (or at low strain rates). (C) 2014 Elsevier Ltd. All rights reserved.

Effects of Microstructure and Loading on Fracture of Sn-3.8Ag-0.7Cu Joints on Cu Substrates with ENIG Surface Finish

When dropped, electronic packages often undergo failure by propagation of an interfacial crack in solder joints under a combination of tensile and shear loading. Hence, it is crucial to understand and predict the fracture behavior of solder joints under mixed-mode high-rate loading conditions. In this work, the effects of the loading conditions (strain rate and loading angle) and microstructure interfacial intermetallic compound (IMC) morphology and solder yield strength] on the mixed-mode fracture toughness of Sn-3.8 wt.%Ag-0.7 wt.%Cu solder joints sandwiched between two Cu substrates with electroless nickel immersion gold (ENIG) metallization have been studied, and compared with the fracture behavior of joints attached to bare Cu. Irrespective of the surface finish, the fracture toughness of the solder joints decreased monotonically with strain rate and mode-mixity, both resulting in increased fracture proportion through the interfacial IMC layer. Furthermore, the proportion of crack propagation through the interfacial IMC layer increased with increase in the thickness and the roughness of the interfacial IMC layer and the yield strength of the solder, resulting in a decrease in the fracture toughness of the joint. However, under most conditions, solder joints with ENIG finish showed higher resistance to fracture than joints attached directly to Cu substrates without ENIG metallization. Based on the experimental observations, a fracture mechanism map is constructed correlating the yield strength of the solder, the morphology and thickness of the interfacial IMC, and the fracture mechanisms as well as the fracture toughness values for different solder joints under mode I loading.

One-pot synthesis of functionalized beta-amino sulfides/beta-amino selenides via ring opening of cyclic sulfamidates

A number of functionalized beta-amino and gamma-amino sulfides and selenides have been synthesized involving a one-pot process of ring opening of cyclic sulfamidates with `in situ' generated thiolate and selenoate species from diaryl disulfides and diphenyl diselenide using rongalite. A mild and efficient method has been developed for the synthesis of cysteines from serine.

Characterization of a dual-active enzyme, DcpA, involved in cyclic diguanosine monophosphate turnover in Mycobacterium smegmatis

We have reported previously that the long-term survival of Mycobacterium smegmatis is facilitated by a dual-active enzyme MSDGC-1 (renamed DcpA), which controls the cellular turnover of cyclic diguanosine monophosphate (c-di-GMP). Most mycobacterial species possess at least a single copy of a DcpA orthologue that is highly conserved in terms of sequence similarity and domain architecture. Here, we show that DcpA exists in monomeric and dimeric forms. The dimerization of DcpA is due to non-covalent interactions between two protomers that are arranged in a parallel orientation. The dimer shows both synthesis and hydrolysis activities, whereas the monomer shows only hydrolysis activity. In addition, we have shown that DcpA is associated with the cytoplasmic membrane and exhibits heterogeneous cellular localization with a predominance at the cell poles. Finally, we have also shown that DcpA is involved in the change in cell length and colony morphology of M. smegmatis. Taken together, our study provides additional evidence about the role of the bifunctional protein involved in c-di-GMP signalling in M. smegmatis.