A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not.

Role of Specific Cations and Water Entropy on the Stability of Branched DNA Motif Structures

DNA three-way junctions (TWJs) are important intermediates in various cellular processes and are the simplest of a family of branched nucleic acids being considered as scaffolds for biomolecular nanotechnology. Branched nucleic acids are stabilized by divalent cations such as Mg2+, presumably due to condensation and neutralization of the negatively charged DNA backbone. However, electrostatic screening effects point to more complex solvation dynamics and a large role of interfacial waters in thermodynamic stability. Here, we report extensive computer simulations in explicit water and salt on a model TWJ and use free energy calculations to quantify the role of ionic character and strength on stability. We find that enthalpic stabilization of the first and second hydration shells by Mg2+ accounts for 1/3 and all of the free energy gain in 50% and pure MgCl2 solutions, respectively. The more distorted DNA molecule is actually destabilized in pure MgCl2 compared to pure NaCl. Notably, the first shell, interfacial waters have very low translational and rotational entropy (i.e., mobility) compared to the bulk, an entropic loss that is overcompensated by increased enthalpy from additional electrostatic interactions with Mg2+. In contrast, the second hydration shell has anomalously high entropy as it is trapped between an immobile and bulklike layer. The nonmonotonic entropic signature and long-range perturbations of the hydration shells to Mg2+ may have implications in the molecular recognition of these motifs. For example, we find that low salt stabilizes the parallel configuration of the three-way junction, whereas at normal salt we find antiparallel configurations deduced from the NMR. We use the 2PT analysis to follow the thermodynamics of this transition and find that the free energy barrier is dominated by entropic effects that result from the decreased surface area of the antiparallel form which has a smaller number of low entropy waters in the first monolayer.

A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not.

Small-Angle Neutron-Scattering Studies of Mixed Micellar Structures Made of Dimeric Surfactants Having Imidazolium and Ammonium Headgroups

Planar imidazolium cation based gemini surfactants 16-Im-n-Im-16], 2Br(-) (where n = 2, 3, 4, 5, 6, 8, 10, and 12), exhibit different morphologies and internal packing arrangements by adopting different supramolecular assemblies in aqueous media depending on their number of spacer methylene units (CH2)(n). Detailed measurements of the small-angle neutron-scattering (SANS) cross sections from different imidazolium-based surfactant micelles in aqueous media (D2O) are reported. The SANS data, containing the information of aggregation behavior of such surfactants in the molecular level, have been analyzed on the basis of the Hayter and Penfold model for the macro ion solution to compute the interparticle structure factor S(Q) taking into account the screened Coulomb interactions between the dimeric surfactant micelles. The characteristic changes in the SANS spectra of the dimeric surfactant with n = 4 due to variation of temperature have also been investigated. These data are then compared with the SANS characterization data of the corresponding gemini micelles containing tetrahedral ammonium ion based polar headgroups. The critical micellar concentration of each surfactant micelle (cmc) has been determined using pyrene as an extrinsic fluorescence probe. The variation of cmc as a function of spacer chain length has been explained in terms of conformational variation and progressive looping of the spacer into the micellar interior upon increasing the n values. Small-angle neutron-scattering (SANS) cross sections from different mixed micelles composed of surfactants with ammonium headgroups, 16-A(0), 16-Am-n-Am-16], 2Br(-) (where n = 4), 16-I-0, and 16-Im-n-Im-16], 2Br(-) (where n = 4), in aqueous media (D2O) have also been analyzed. The aggregate composition matches with that predicted from the ideal mixing model.

MPI-based parallel synchronous vector evaluated particle swarm optimization for multi-objective design optimization of composite structures

This paper presents a decentralized/peer-to-peer architecture-based parallel version of the vector evaluated particle swarm optimization (VEPSO) algorithm for multi-objective design optimization of laminated composite plates using message passing interface (MPI). The design optimization of laminated composite plates being a combinatorially explosive constrained non-linear optimization problem (CNOP), with many design variables and a vast solution space, warrants the use of non-parametric and heuristic optimization algorithms like PSO. Optimization requires minimizing both the weight and cost of these composite plates, simultaneously, which renders the problem multi-objective. Hence VEPSO, a multi-objective variant of the PSO algorithm, is used. Despite the use of such a heuristic, the application problem, being computationally intensive, suffers from long execution times due to sequential computation. Hence, a parallel version of the PSO algorithm for the problem has been developed to run on several nodes of an IBM P720 cluster. The proposed parallel algorithm, using MPI's collective communication directives, establishes a peer-to-peer relationship between the constituent parallel processes, deviating from the more common master-slave approach, in achieving reduction of computation time by factor of up to 10. Finally we show the effectiveness of the proposed parallel algorithm by comparing it with a serial implementation of VEPSO and a parallel implementation of the vector evaluated genetic algorithm (VEGA) for the same design problem. (c) 2012 Elsevier Ltd. All rights reserved.

Crowding, molecular volume and plasticity: An assessment involving crystallography, NMR and simulations

The discrepancy between the X-ray and NMR structures of Mycobacterium tuberculosis peptidyl-tRNA hydrolase in relation to the functionally important plasticity of the molecule led to molecular dynamics simulations. The X-ray and the NMR studies along with the simulations indicated an inverse correlation between crowding and molecular volume. A detailed comparison of proteins for which X-ray and the NMR structures appears to confirm this correlation. In consonance with the reported results of the investigations in cellular compartments and aqueous solution, the comparison indicates that the crowding results in compaction of the molecule as well as change in its shape, which could specifically involve regions of the molecule important in function. Crowding could thus influence the action of proteins through modulation of the functionally important plasticity of the molecule. Selvaraj M, Ahmad R, Varshney U and Vijayan M 2012 Crowding, molecular volume and plasticity: An assessment involving crystallography, NMR and simulations. J. Biosci. 37 953-963] DOI 10.1007/s12038-012-9276-5

Efficient external memory structures for range-aggregate queries

We present external memory data structures for efficiently answering range-aggregate queries. The range-aggregate problem is defined as follows: Given a set of weighted points in R-d, compute the aggregate of the weights of the points that lie inside a d-dimensional orthogonal query rectangle. The aggregates we consider in this paper include COUNT, sum, and MAX. First, we develop a structure for answering two-dimensional range-COUNT queries that uses O(N/B) disk blocks and answers a query in O(log(B) N) I/Os, where N is the number of input points and B is the disk block size. The structure can be extended to obtain a near-linear-size structure for answering range-sum queries using O(log(B) N) I/Os, and a linear-size structure for answering range-MAX queries in O(log(B)(2) N) I/Os. Our structures can be made dynamic and extended to higher dimensions. (C) 2012 Elsevier B.V. All rights reserved.

Updating reliability models of statically loaded instrumented structures

The study extends the first order reliability method (FORM) and inverse FORM to update reliability models for existing, statically loaded structures based on measured responses. Solutions based on Bayes' theorem, Markov chain Monte Carlo simulations, and inverse reliability analysis are developed. The case of linear systems with Gaussian uncertainties and linear performance functions is shown to be exactly solvable. FORM and inverse reliability based methods are subsequently developed to deal with more general problems. The proposed procedures are implemented by combining Matlab based reliability modules with finite element models residing on the Abaqus software. Numerical illustrations on linear and nonlinear frames are presented. (c) 2012 Elsevier Ltd. All rights reserved.

Synthesis and structural characterization of two-dimensional hierarchical covellite nano-structures

We report a simple, template free and low-temperature hydrothermal reaction pathway using Cu(II) - thiourea complex (prepared in situ from copper (II) chloride and thiourea as precursors) and citric acid as complexing agent to synthesize two-dimensional hierarchical nano-structures of covellite (CuS). The product was characterized with the help of X-ray powder diffraction (XRD), scanning electron microscopy (SEM), energy dispersive analysis of X-ray spectroscopy (EDAX) and X-ray photoelectron spectroscopy (XPS). The concentration of citric acid in the hydrothermal precursor solution was seen to have a profound effect on the nanostructure of the product generated. Based on the outcoming product nano-architecture at different concentration of the ionic surfactant in the hydrothermal precursor solution a possible mechanism suited for reaction and further nucleation is also discussed. (C) 2012 Elsevier B.V. All rights reserved.

Compositionally Graded Microstructure for Ag-Fe Nanoparticles

Ag-Fe nanoparticles with a highly Ag rich average composition were synthesized by the sonochemical route. Silver-iron system exhibits a wide miscibility gap in the bulk materials. Interestingly, a graded compositional profile along the nanoparticle radius was observed. Regions at and near the surface of the nanoparticle contained both Ag and Fe atoms. The composition got relatively deficient Fe towards the center of the particle with particle core made up of pure Ag. Alloying of Ag and Fe is confirmed by the absence of diffraction signal corresponding to pure Fe phase and presence of a paramagnetic phase in nanoparticles containing a diamagnetic (Ag) and ferromagnetic (Fe) elements.

Crystal Structures and Physicochemical Properties of Four New Lamotrigine Multicomponent Forms

In the present study, four new multicomponent forms of lamotrigine (LTG) with selected carboxylic acids, viz. acetic acid, propionic acid, sorbic acid, and glutaric acid, have been identified. Preliminary solid-state characterization was done by differential scanning calorimetry/thermogravimetric, infrared, and powder X-ray diffraction techniques. X-ray single-crystal structure analysis confirmed the proton transfer, stoichiometry, and the molecular composition, revealing all of these to be a new salt/salt-cocrystal/salt monosolvate monohydrate of LTG. All four compounds exhibited both the aminopyridine dimer of LTG (motif 4) and cation-anion dimers between protonated LTG and the carboxylate anion in their crystal structures. Further, these new crystal forms were subjected to solubility studies in water, powder dissolution studies in 0.1 N HCl, and stability studies under humid conditions in comparison with pure LTG base. The solubility of these compounds in water is significantly enhanced compared with that of pure base, which is attributed to the type of packing motifs present in their crystal structures as well as to the lowering of the pH by the acidic coformers. Solid residues of all forms remaining after solubility and dissolution experiments were also assessed for any transformation in water and acidic medium.

Self-Adapting Peripherally Heterofunctionalized Hyperbranched Polymers: Formation of Janus and Tripodal Structures

A peripherally clickable hyperbranched polyester carrying numerous propargyl terminal groups was prepared by a simple melt transesterification polycondensation of a suitably designed AB(2) monomer; this clickable hyperscaffold was then transformed into a variety of different derivatives by using the Cu-catalyzed azide-yne click reaction. Functionalization of the periphery with equimolar quantities of mutually immiscible segments, such as hydrocarbon, fluorocarbon, and PEG, yielded frustrated molecular systems that readapt and form structures wherein the immiscible segments appear to self-segregate to generate either Janus structures (when two immiscible segments are present) or tripodal structures (when three immiscible segments are present). Evidence for such self-segregation was obtained from a variety of studies, such as differential scanning calorimetry, Langmuir isotherms, AFM imaging, and small-angle X-ray scattering measurements. Crystallization of one or more of the peripheral segments reinforced this self-segregation; the weight-fraction-normalized enthalpies of melting associated with the different domains revealed a competition between the segments to optimize their crystalline organization. When one or more of the segments are amorphous, the remaining segments crystallize more effectively and consequently exhibit a higher melting enthalpy. AFM images of monolayers, transferred from the Langmuir trough, revealed that the thickness matches the expected values; furthermore, contact angle measurements clearly demonstrated that the monolayer films are fairly hydrophobic, and in the case of the tripodal hybramers, the presence of domains of hydrocarbon and fluorocarbon appears to impart nanoscale chemical heterogeneity that is reflected in the strong hysteresis in the advancing and receding contact angles.

COMPARATIVE EVALUATION OF THERMAL CONDUCTIVITY OF ZIRCONIA SOLID AND HONEYCOMB STRUCTURES

Porous zirconia ceramic monoliths have been extensively used in thermo-structural applications due to their inherent low thermal conductivity in combination with their adaptability to form complicated shapes through advanced ceramic processing techniques. However, extruded cellular honeycomb structures made from these materials have been less explored for thermal management applications. There exist large potential applications due to their unique configurations, resulting in better heat-management mechanisms. Some of the studies carried out on zirconia honeycombs are safeguarded through patents due to its technical importance, or the information is not in the public domain. In the present study, for the sake of comparison, honeycomb specimens with varying wall thicknesses and unit cell lengths maintaining almost same bulk density of around 90% theoretical and relative density of 0.34-0.37 were prepared and subjected to thermal conductivity evaluation along with the solid samples with relative density of 1.0 using monotonic heating regime methodology. In addition, the effect of channel shape was also evaluated using square and triangular channeled honeycombs with the same relative densities. The results obtained from these specimens were correlated with their configurations to bring out the advantages accrued by using the honeycomb with these configurations. It was observed that a significant decrease in thermal conductivity was achieved in honeycombs, which can be attributed to the behavior of various heat transfer mechanisms that are operative at high temperatures in combination with the considerable reduction in thermal mass and the consequent conduction through the solids.

Dramatic Structural Changes Resulting from the Loss of a Crucial Hydrogen Bond in the Hinge Region Involved in C-Terminal Helix Swapping in SurE: A Survival Protein from Salmonella typhimurium

Domain swapping is an interesting feature of some oligomeric proteins in which each protomer of the oligomer provides an identical surface for exclusive interaction with a segment or domain belonging to another protomer. Here we report results of mutagenesis experiments on the structure of C-terminal helix swapped dimer of a stationary phase survival protein from Salmonella typhimurium (StSurE). Wild type StSurE is a dimer in which a large helical segment at the C-terminus and a tetramerization loop comprising two beta strands are swapped between the protomers. Key residues in StSurE that might promote C-terminal helix swapping were identified by sequence and structural comparisons. Three mutants in which the helix swapping is likely to be avoided were constructed and expressed in E. coli. Three-dimensional X-ray crystal structures of the mutants H234A and D230A/H234A could be determined at 2.1 angstrom and 2.35 angstrom resolutions, respectively. Contrary to expectations, helix swapping was mostly retained in both the mutants. The loss of the crucial D230 OD2- H234 NE2 hydrogen bond (2.89 angstrom in the wild type structure) in the hinge region was compensated by new inter and intra-chain interactions. However, the two fold molecular symmetry was lost and there were large conformational changes throughout the polypeptide. In spite of these changes, the dimeric structure and an approximate tetrameric organization were retained, probably due to the interactions involving the tetramerization loop. Mutants were mostly functionally inactive, highlighting the importance of precise inter-subunit interactions for the symmetry and function of StSurE.

Cu-II-azide polynuclear complexes of Cu-4 building clusters with Schiff-base co-ligands: synthesis, structures, magnetic behavior and DFT studies

Three new copper-azido complexes Cu-4(N-3)(8)(L-1)(2)](n) (1), Cu-4(N-3)(6)(L-2)(2)(H2O)(2)] (2), and Cu-4(N-3)(6)(L-3)(2)](n) (3) L-1 is the imine resulting from the condensation of pyridine-2-carboxaldehyde with N-methylethylenediamine, HL2 and HL3 are the condensation products of 2-hydroxy-3-methoxybenzaldehyde with N,N-diethylethylenediamine and N-ethylethylenediamine respectively] have been synthesized by using 0.5 molar equivalents of the Schiff base ligands with Cu(NO3)(2)center dot 3H(2)O and an excess of NaN3. Single crystal X-ray structures show that the basic unit of these complexes contains very similar Cu-4(II) building blocks. While 1 and 3 have overall 1D structures, 2 forms discrete tetranuclear clusters due to blocking of two coordination sites on the tetranuclear cluster by water molecules. Magnetic susceptibility measurements over a wide range of temperatures exhibit the presence of both antiferromagnetic and ferromagnetic exchanges within the tetranuclear unit structures. Density functional theory calculations (using B3LYP functional and two different basis sets) have been performed on the complexes 1-3 to provide a qualitative theoretical interpretation of their overall magnetic behavior.