Method for Seismic Microzonation with Geotechnical Aspects

This study presents an overview of seismic microzonation and existing methodologies with a newly proposed methodology covering all aspects. Earlier seismic microzonation methods focused on parameters that affect the structure or foundation related problems. But seismic microzonation has generally been recognized as an important component of urban planning and disaster management. So seismic microzonation should evaluate all possible hazards due to earthquake and represent the same by spatial distribution. This paper presents a new methodology for seismic microzonation which has been generated based on location of study area and possible associated hazards. This new method consists of seven important steps with defined output for each step and these steps are linked with each other. Addressing one step and respective result may not be seismic microzonation, which is practiced widely. This paper also presents importance of geotechnical aspects in seismic microzonation and how geotechnical aspects affect the final map. For the case study, seismic hazard values at rock level are estimated considering the seismotectonic parameters of the region using deterministic and probabilistic seismic hazard analysis. Surface level hazard values are estimated considering site specific study and local site effects based on site classification/characterization. The liquefaction hazard is estimated using standard penetration test data. These hazard parameters are integrated in Geographical Information System (GIS) using Analytic Hierarchy Process (AHP) and used to estimate hazard index. Hazard index is arrived by following a multi-criteria evaluation technique - AHP, in which each theme and features have been assigned weights and then ranked respectively according to a consensus opinion about their relative significance to the seismic hazard. The hazard values are integrated through spatial union to obtain the deterministic microzonation map and probabilistic microzonation map for a specific return period. Seismological parameters are widely used for microzonation rather than geotechnical parameters. But studies show that the hazard index values are based on site specific geotechnical parameters.

Phase synchronization in brain networks derived from correlation between probabilities of recurrences in functional MRI data

It is increasingly being recognized that resting state brain connectivity derived from functional magnetic resonance imaging (fMRI) data is an important marker of brain function both in healthy and clinical populations. Though linear correlation has been extensively used to characterize brain connectivity, it is limited to detecting first order dependencies. In this study, we propose a framework where in phase synchronization (PS) between brain regions is characterized using a new metric ``correlation between probabilities of recurrence'' (CPR) and subsequent graph-theoretic analysis of the ensuing networks. We applied this method to resting state fMRI data obtained from human subjects with and without administration of propofol anesthetic. Our results showed decreased PS during anesthesia and a biologically more plausible community structure using CPR rather than linear correlation. We conclude that CPR provides an attractive nonparametric method for modeling interactions in brain networks as compared to standard correlation for obtaining physiologically meaningful insights about brain function.

Cytochrome P450-mediated metabolism in brain: functional roles and their implications

Introduction: Cytochromes P450 (P450) and associated monooxygenases are a family of heme proteins involved in metabolism of endogenous compounds (arachidonic acid, eicosanoids and prostaglandins) as also xenobiotics including drugs and environmental chemicals. Liver is the major organ involved in P450-mediated metabolism and hepatic enzymes have been characterized. Extrahepatic organs, such as lung, kidney and brain have the capability for biotransformation through P450 enzymes. Brain, including human brain, expresses P450 enzymes that metabolize xenobiotics and endogenous compounds. Areas covered: An overview of P450-mediated metabolism in brain is presented focusing on distinct differences seen in expression of P450 enzymes, generation of unique P450 enzymes in brain through alternate splicing and their consequences in terms of metabolism of psychoactive drugs and inflammatory prompts, such as leukotrienes, thus modulating inflammatory response. Expert opinion: The brain possesses unique P450s that metabolize drugs and endogenous compounds through pathways that are markedly different from that seen in liver indicating that extrapolation directly from liver to brain is not appropriate. It is therefore necessary to characterize the unique brain P450s and their ability to metabolize xenobiotics and endogenous compounds to better understand the functions of this important class of enzymes in brain, especially human brain.

Diaminotriazine substituted diphenyl ether: reversible structural transformation and solvent dependent solid state fluorescence

The effect of molecular shape and position of hydrogen bonding functionality in the solid state structural self-assembly was investigated using diaminotriazine substituted diphenyl ether based positional isomers (1-5). The molecular shape was modulated by changing diaminotriazine position that produced channel supramolecular structures in 1, 3 and 5. There exists a direct correlation between the molecular shape and three dimensional structures; more linear molecules resulted in close-packing whereas molecules with a labyrinthine topology formed a channel structure. Supramolecular aspects pertaining to the influence of solvent of crystallization in structure formation and reversible structural transformation in solid state were also explored. 1-5 exhibited tunable solid state fluorescence (lambda(max) = 437-496 nm) depending on the diaminotriazine substitutional position and 3 showed solvent-dependent solid state fluorescence. The present study describes the generation of a supramolecular channel structure with functional properties such as tunable fluorescence by varying the position of hydrogen bond functionality and solvent of crystallization.

Influence of steric effect on the structural aspects of N,N `,N `'-triarylguanidine derived six-membered C,N] palladacycles

Guanidine derived six-membered C,N] palladacycles of the types (C,N)Pd(mu-OC(O)R)](2) (1a-d), (C,N)Pd(mu-Br)](2) (2a,b), cis-(C,N)PdBr(L)] (3a-d, 4, and 5), and ring contracted guanidine derived five-membered C,N] palladacycle, (C,N)PdBr(C NXy)] (6) were prepared in high yield following the established methods with a view aimed at understanding the influence of the substituents on the aryl rings of the guanidine upon the solid state structure and solution behaviour of palladacycles. Palladacycles were characterised by microanalytical, IR, NMR and mass spectral data. The molecular structures of 1a, 1c, 2a, 2b, 3a, 3c, 3d, and 4-6 were determined by single crystal X-ray diffraction data. Palladacycles 1a and 1c were shown to exist as a dimer in transoid in-in conformation in the solid state but as a mixture of a dimer in major proportion and a monomer (kappa(2)-O,O'-OAc) in solution as deduced from H-1 NMR data. Palladacycles 2a and 2b were shown to exist as a dimer in transoid conformation in the solid state but the former was shown to exist as a mixture of a dimer and presumably a trimer in solution as revealed by a variable temperature H-1 NMR data in conjunction with ESI-MS data. The cis configuration around the palladium atom in 3a, 3c, and 3d was ascribed to steric influence of the aryl moiety of =NAr unit and that in 4-6 was ascribed to antisymbiosis. The solution behaviour of 3d was studied by a variable concentration (VC) H-1 NMR data.

Identification of an exported heat shock protein 70 in Plasmodium falciparum

Host cell remodelling is a hallmark of malaria pathogenesis. It involves protein folding, unfolding and trafficking events and thus participation of chaperones such as Hsp70s and Hsp40s is well speculated. Until recently, only Hsp40s were thought to be the sole representative of the parasite chaperones in the exportome. However, based on the re-annotated Plasmodium falciparum genome sequence, a putative candidate for exported Hsp70 has been reported, which otherwise was known to be a pseudogene. We raised a specific antiserum against a C-terminal peptide uniquely present in PfHsp70-x. Immunoblotting and immunofluorescence-based approaches in combination with sub-cellular fractionation by saponin and streptolysin-O have been taken to determine the expression and localization of PfHsp70-x in infected erythrocyte. The re-annotated sequence of PfHsp70-x reveals it to be a functional protein with an endoplasmic reticulum signal peptide. It gets maximally expressed at the schizont stage of intra-erythrocytic life cycle. Majority of the protein localizes to the parasitophorous vacuole and some of it gets exported to the erythrocyte compartment where it associates with Maurer's clefts. The identification of an exported parasite Hsp70 chaperone presents us with the fact that the parasite has evolved customized chaperones which might be playing crucial roles in aspects of trafficking and host cell remodelling.

A tuned rectifier for RF energy harvesting from ambient radiations

A circuit topology based on accumulate-and-use philosophy has been developed to harvest RF energy from ambient radiations such as those from cellular towers. Main functional units of this system are antenna, tuned rectifier, supercapacitor, a gated boost converter and the necessary power management circuits. Various RF aspects of the design philosophy for maximizing the conversion efficiency at an input power level of 15 mu W are presented here. The system is characterized in an anechoic chamber and it has been established that this topology can harvest RF power densities as low as 180 mu W/m(2) and can adaptively operate the load depending on the incident radiation levels. The output of this system can be easily configured at a desired voltage in the range 2.2-4.5 V. A practical CMOS load - a low power wireless radio module has been demonstrated to operate intermittently by this approach. This topology can be easily modified for driving other practical loads, from harvested RF energy at different frequencies and power levels.

Heat and SDS insensitive NDK dimers are largely stabilised by hydrophobic interaction to form functional hexamer in Mycobacterium smegmatis

The primary structure and function of nucleoside diphosphate kinase (NDK), a substrate non-specific enzyme involved in the maintenance of nucleotide pools is also implicated to play pivotal roles in many other cellular processes. NDK is conserved from bacteria to human and forms a homotetramer or hexamer to exhibit its biological activity. However, the nature of the functional oligomeric form of the enzyme differs among different organisms. The functional form of NDKs from many bacterial systems, including that of the human pathogen, Mycobacterium tuberculosis (MtuNDK), is a hexamer, although some bacterial NDKs are tetrameric in nature. The present study addresses the oligomeric property of MsmNDK and how a dimer, the basic subunit of a functional hexamer, is stabilized by hydrogen bonds and hydrophobic interactions. Homology modeling was generated using the three-dimensional structure of MtuNDK as a template; the residues interacting at the monomer-monomer interface of MsmNDK were mapped. Using recombinant enzymes of wild type, catalytically inactive mutant, and monomer-monomer interactive mutants of MsmNDK, the stability of the dimer was verified under heat, SDS, low pH, and methanol. The predicted residues (Gln17, Ser24 and Glu27) were engaged in dimer formation, however the mutated proteins retained the ATPase and GTPase activity even after introducing single (MsmNDK- Q17A, MsmNDK-E27A, and MsmNDK-E27Q) and double (MsmNDK-E27A/Q17A) mutation. However, the monomer monomer interaction could be abolished using methanol, indicating the stabilization of the monomer-monomer interaction by hydrophobic interaction.

Six-membered C,N] cyclopalladated sym N,N `,N `'-tri(4-tolyl) guanidines: Synthesis, reactivity studies and structural aspects

Six-membered C,N] cyclopalladated sym N,N',N `'-tri(4-tolyl)guanidines, (ArNH)(2)C=NAr] (sym = symmetrical; Ar = 4-MeC6H4; LH24-tolyl) of the types (C,N)Pd(mu-OC(O)R)](2) (1 and 2), (C,N)Pd(mu-Br)](2) (3), cis-(C,N)PdLBr] (4-7), and (C,N)Pd(acac)] (8) were prepared in high yield by established methods with a view aimed at understanding the influence of the 4-tolyl substituent of the guanidine moiety upon the solution behaviour of 1-8. The composition of 1-8 was confirmed by elemental analysis, IR, and NMR spectroscopy, and mass spectrometry. The molecular structures of 1-6 were determined by single-crystal X-ray diffraction. Palladacycles 1-3 exist as a dimer in transoid conformation in the solid state while 4-6 exist as a monomer with cis configuration around the palladium atom as the Lewis base is placed cis to the Pd-C bond due to antisymbiosis. The NMR spectra of 1-8 revealed the presence of a single isomer in solution and this spectral feature is ascribed to the rapid inversion of the six-membered ``C,N]Pd'' ring due to the presence of sterically less hindered and more symmetrical 4-tolyl substituent in the =NAr unit of the guanidine moiety. (C) 2013 Elsevier B.V. All rights reserved.

Gap renormalization of molecular crystals from density-functional theory

Fundamental gap renormalization due to electronic polarization is a basic phenomenon in molecular crystals. Despite its ubiquity and importance, all conventional approaches within density-functional theory completely fail to capture it, even qualitatively. Here, we present a new screened range-separated hybrid functional, which, through judicious introduction of the scalar dielectric constant, quantitatively captures polarization-induced gap renormalization, as demonstrated on the prototypical organic molecular crystals of benzene, pentacene, and C-60. This functional is predictive, as it contains system-specific adjustable parameters that are determined from first principles, rather than from empirical considerations.

Energy Hyperspace for Stacking Interaction in AU/AU Dinucleotide Step: Dispersion-Corrected Density Functional Theory Study

Double helical structures of DNA and RNA are mostly determined by base pair stacking interactions, which give them the base sequence-directed features, such as small roll values for the purine-pyrimidine steps. Earlier attempts to characterize stacking interactions were mostly restricted to calculations on fiber diffraction geometries or optimized structure using ab initio calculations lacking variation in geometry to comment on rather unusual large roll values observed in AU/AU base pair step in crystal structures of RNA double helices. We have generated stacking energy hyperspace by modeling geometries with variations along the important degrees of freedom, roll, and slide, which were chosen via statistical analysis as maximally sequence dependent. Corresponding energy contours were constructed by several quantum chemical methods including dispersion corrections. This analysis established the most suitable methods for stacked base pair systems despite the limitation imparted by number of atom in a base pair step to employ very high level of theory. All the methods predict negative roll value and near-zero slide to be most favorable for the purine-pyrimidine steps, in agreement with Calladine's steric clash based rule. Successive base pairs in RNA are always linked by sugar-phosphate backbone with C3-endo sugars and this demands C1-C1 distance of about 5.4 angstrom along the chains. Consideration of an energy penalty term for deviation of C1-C1 distance from the mean value, to the recent DFT-D functionals, specifically B97X-D appears to predict reliable energy contour for AU/AU step. Such distance-based penalty improves energy contours for the other purine-pyrimidine sequences also. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 107-120, 2014.

Functional specificity among yeast mitochondrial Hsp70s paralogs and orthologs

The evolutionary diversity of the HSP70 gene family at the genetic level has generated complex structural variations leading to altered functional specificity and mode of regulation in different cellular compartments. By utilizing Saccharomyces cerevisiae as a model system for better understanding the global functional cooperativity between Hsp70 paralogs, we have dissected the differences in functional properties at the biochemical level between mitochondrial heat shock protein 70 (mtHsp70) Ssc1 and an uncharacterized Ssc3 paralog. Based on the evolutionary origin of Ssc3 and a high degree of sequence homology with Ssc1, it has been proposed that both have a close functional overlap in the mitochondrial matrix. Surprisingly, our results demonstrate that there is no functional cross-talk between Ssc1 and Ssc3 paralogs. The lack of in vivo functional overlap is due to altered conformation and significant lower stability associated with Ssc3. The substrate-binding domain of Ssc3 showed poor affinity toward mitochondrial client proteins and Tim44 due to the open conformation in ADP-bound state. In addition to that, the nucleotide-binding domain of Ssc3 showed an altered regulation by the Mge1 co-chaperone due to a high degree of conformational plasticity, which strongly promotes aggregation. Besides, Ssc3 possesses a dysfunctional inter-domain interface thus rendering it unable to perform functions similar to generic Hsp70s. Moreover, we have identified the critical amino acid sequence of Ssc1 and Ssc3 that can “make or break” mtHsp70 chaperone function. Together, our analysis provides the first evidence to show that the nucleotide-binding domain of mtHsp70s plays a critical role in determining the functional specificity among paralogs and orthologs across kingdoms.

Molecular flexibility of Mycobacterium tuberculosis ribosome recycling factor and its functional consequences: An exploration involving mutants

Internal mobility of the two domain molecule of ribosome recycling factor (RRF) is known to be important for its action. Mycobacterium tuberculosis RRF does not complement E. coli for its deficiency of RRF (in the presence of E. coli EF-G alone). Crystal structure had revealed higher rigidity of the M. tuberculosis RRF due to the presence of additional salt bridges between domains. Two inter-domain salt bridges and one between the linker region and the domain containing C-terminal residues were disrupted by appropriate mutations. Except for a C-terminal deletion mutant, all mutants showed RRF activity in E. coli when M. tuberculosis EF-G was also co-expressed. The crystal structures of the point mutants, that of the C-terminal deletion mutant and that of the protein grown in the presence of a detergent, were determined. The increased mobility resulting from the disruption of the salt bridge involving the hinge region allows the appropriate mutant to weakly complement E. coli for its deficiency of RRF even in the absence of simultaneous expression of the mycobacterial EF-G. The loss of activity of the C-terminal deletion mutant appears to be partly due to the rigidification of the molecule consequent to changes in the hinge region.

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.