Synthesis and Structure-Activity Correlation Studies of Secondary- and Tertiary-Amine-Based Glutathione Peroxidase Mimics

In this study, a series of seeondary- and tertiary-amino-substituted diaryl diselenides were synthesized and studied for their glutathione peroxidase (GPx) like antioxidant activities with H2O2, cumene hydroperoxide, or tBuOOH as substrates and with PhSH or glutathione (GSH) as thiol cosubstrates. This study reveals that replacement of the tert-amino groups in benzylamine-based diselenides by sec-amino moieties drastically enhances the catalytic activities in both the aromatic thiol (PhSH) and GSH assay systems. Particularly, the N-propyl- and N-isopropylamino-substituted diselenides are 8-18 times more active than the corresponding N,N-dipropyl- and N,N-diisopropylamine-based compounds in all three peroxide systems when GSH is used as the thiol cosubstrate. Although the catalytic mechanism of sec-amino-substituted disclenides is similar to that of the tert-amine-based compounds, differences in the stability and reactivity of some of the key intermediates account for the differences in the GPx-like activities. it is observed that the sec-amino groups are better than the tert-amino moieties for generating the catalytically active selenols. This is due to the absence of any significant thiol-exchange reactions in the selenenyl sulfides derived from sec-amine-based diselenides. Furthermore, the seleninic acids (RSeO2H) derived from the sec-amine-based compounds are more stable toward further reactions with peroxides than their tert-amine-based analogues.

Conformational Choices for the Stereochemically Constrained gamma-Amino Acid Residue Gabapentin: Theoretical Studies and Correlation With Experimental Results

Gabapentin (1-aminomethylcyclohexaneacetic acid, Gpn) is an achiral, conformationally constrained gamma amino acid residue. A survey of available crystal structures of Gpn peptides reveals that the torsion angles about the C-gamma-C-beta (theta(1)) and C-beta-C-alpha(theta(2)) bonds are overwhelmingly limited to gauche, gauche (g(+)g(+)/g(-)g(-)) conformations. The Gpn residue forms C-7 and C-9 hydrogen bonds in which the donor and acceptor atoms come from the flanking peptide units. In combination with alpha amino acid residues alpha gamma and gamma alpha segments can adopt C-12 hydrogen bonded structures. The conformational choices available to the Gpn residue have been probed using energy calculations, adopting a grid search strategy. Ramachandran phi-psi maps have been constructed for fixed values of theta(1) and theta(2), corresponding to the gauche and trans conformations. The sterically allowed and energetically favorable regions of conformational space have been defined and experimental observations compared. C-7 and C-9 hydrogen bonded conformational families have been identified using a grid search approach in which theta(1) and theta(2) values are varied over a range of +/- 10 degrees about ideal values at 1 degrees intervals. The theoretical analysis together with experimental observations for 59 Gpn residues from 35 crystal structures permits definition of the limited range of conformational possibilities at this gamma amino acid residue. .

Spatial correlation in grain misorientation distribution

Grain misorientation was studied in relation to the nearest neighbor's mutual distance using electron back-scattered diffraction measurements. The misorientation correlation function was defined as the probability density for the occurrence of a certain misorientation between pairs of grains separated by a certain distance. Scale-invariant spatial correlation between neighbor grains was manifested by a power law dependence of the preferred misorientation vs. inter-granular distance in various materials after diverse strain paths. The obtained negative scaling exponents were in the range of -2 +/- 0.3 for high-angle grain boundaries. The exponent decreased in the presence of low-angle grain boundaries or dynamic recrystallization, indicating faster decay of correlations. The correlations vanished in annealed materials. The results were interpreted in terms of lattice incompatibility and continuity conditions at the interface between neighboring grains. Grain-size effects on texture development, as well as the implications of such spatial correlations on texture modeling, were discussed.

Observation of the intense de-pairing effect in YBa2Cu3O7-delta due to the spin injection from La0.5Sr0.5CoO3

We report experimental evidence for a huge pair breaking effect induced by spin polarized quasiparticles in a YBa2Cu3O7-delta/La0.5Sr0.5CoO3 bi-layer fabricated by pulsed laser deposition. The temperature dependent magnetization measurements show evidence for the presence of both ferromagnetic and diamagnetic phases in the bi-layer. The current dependent electrical transport studies in the bi-layer exhibit a significant reduction in the superconducting transition temperature with the increase in applied current as compared to a single YBa2Cu3O7-delta layer and it follows a I-2/3 dependence in accordance with the pair breaking effect. Here, we find that the current driven from a ferromagnetic electrode with low spin polarization, such as La0.5Sr0.5CoO3 (-11%), into the superconductor can act as a strong pair breaker. This indicates that the spin polarization of the injecting electrode is not the only criterion in determining the pair breaking effect, rather the transparency of the interface for the spin polarization may also be significant. More interestingly, the spin diffusion length for YBa2Cu3O7-delta has a much longer length scale than that reported earlier in the study of ferromagnetic/superconducting heterostructures.

RecA Protein of Mycobacterium tuberculosis Possesses pH-Dependent Homologous DNA Pairing and Strand Exchange Activities: Implications for Allele Exchange in Mycobacteria

To gain insights into inefficient allele exchange in mycobacteria, we compared homologous pairing and strand exchange reactions promoted by RecA protein of Mycobacterium tuberculosis to those of Escherichia coli RecA protein. The extent of single-stranded binding protein (SSB)-stimulated formation of joint molecules by MtRecA was similar to that of EcRecA over a wide range of pH values. In contrast, strand exchange promoted by MtRecA was inhibited around neutral pH due to the formation of DNA networks. At higher pH, MtRecA was able to overcome this constraint and, consequently, displayed optimal strand exchange activity. Order of addition experiments suggested that SSB, when added after MtRecA, was vital for strand exchange. Significantly, with shorter duplex DNA, MtRecA promoted efficient strand exchange without network formation in a pH-independent fashion. Increase in the length of duplex DNA led to incomplete strand exchange with concomitant rise in the formation of intermediates and networks in a pH-dependent manner. Treatment of purified networks with S1 nuclease liberated linear duplex DNA and products, consistent with a model in which the networks are formed by the invasion of hybrid DNA by the displaced linear single-stranded DNA. Titration of strand exchange reactions with ATP or salt distinguished a condition under which the formation of networks was blocked, but strand exchange was not significantly affected. We discuss how these results relate to inefficient allele exchange in mycobacteria.

Use of structure-directed DNA ligands to probe the binding of recA protein to narrow and wide grooves of DNA and on its ability to promote homologous pairing

We have used circular dichroism and structure-directed drugs to identify the role of structural features, wide and narrow grooves in particular, required for the cooperative polymerization, recognition of homologous sequences, and the formation of joint molecules promoted by recA protein. The path of cooperative polymerization of recA protein was deduced by its ability to cause quantitative displacement of distamycin from the narrow groove of duplex DNA. By contrast, methyl green bound to the wide groove was retained by the nucleoprotein filaments comprised of recA protein-DNA. Further, the mode of binding of these ligands and recA protein to DNA was confirmed by DNaseI digestion. More importantly, the formation of joint molecules was prevented by distamycin in the narrow groove while methyl green in the wide groove had no adverse effect. Intriguingly, distamycin interfered with the production of coaggregates between nucleoprotein filaments of recA protein-M13 ssDNA and naked linear M13 duplex DNA, but not with linear phi X174 duplex DNA. Thus, these data, in conjunction with molecular modeling, suggest that the narrow grooves of duplex DNA provide the fundamental framework required for the cooperative polymerization of recA protein and alignment of homologous sequences. These findings and their significance are discussed in relation to models of homologous pairing between two intertwined DNA molecules.

DNA-induced conformational changes in RecA protein. Evidence for structural heterogeneity among nucleoprotein filaments and implications for homologous pairing

We have used circular dichroism as a probe to characterize the solution conformational changes in RecA protein upon binding to DNA. This approach revealed that RecA protein acquires significant amounts of alpha-helix upon interaction with DNA. These observations, consistent with the data from crystal structure (Story, R. M., Weber, I., and Steitz, T. (1992) Nature 355, 318-325), support the notion that some basic domains including the DNA binding motifs of RecA protein are unstructured and might contribute to the formation of alpha-helix. A comparison of nucleoprotein filaments comprised of RecA protein and a variety of DNA substrates revealed important structural heterogeneity. The most significant difference was observed with poly(dG). poly(dC) and related polymers, rich in GC sequences, which induced minimal amounts of alpha-helix in RecA protein. The magnitude of induction of alpha-helix in RecA protein, which occurred concomitant with the production of ternary complexes, was 2-fold higher with homologous than heterologous duplex DNA. Most importantly, the stimulation of ATP hydrolysis by high salt coincided with that of the induction of alpha-helix in RecA protein. These conformational differences provide a basis for thinking about the biochemical and structural transitions that RecA protein experiences during the formal steps of presynapsis, recognition, and alignment of homologous sequences.

The homologous recombination system of phage lambda. Pairing activities of beta protein

The red genes of phage lambda specify two proteins, exonuclease and beta protein, which are essential for its general genetic recombination in recA- cells. These proteins seem to occur in vivo as an equimolar complex. In addition, beta protein forms a complex with another polypeptide, probably of phage origin, of Mr 70,000. The 70-kDa protein appears to be neither a precursor nor an aggregated form of either exonuclease or beta protein, since antibodies directed against the latter two proteins failed to react with 70-kDa protein on Ouchterlony double diffusion analysis. beta protein promotes Mg2+-dependent renaturation of complementary strands (Kmiec, E., and Holloman, W. K. (1981) J. Biol. Chem. 256, 12636-12639). To look for other pairing activities of beta protein, we developed methods of purification to free it of associated exonuclease. Exonuclease-free beta protein appeared unable to cause the pairing of a single strand with duplex DNA; however, like Escherichia coli single strand binding protein (SSB), beta protein stimulated formation of joint molecules by recA protein from linear duplex DNA and homologous circular single strands. Like recA protein, but unlike SSB, beta protein promoted the joining of the complementary single-stranded ends of phage lambda DNA. beta protein specifically protected single-stranded DNA from digestion by pancreatic DNase. The half-time for renaturation catalyzed by beta protein was independent of DNA concentration, unlike renaturation promoted by SSB and spontaneous renaturation, which are second order reactions. Thus, beta protein resembles recA protein in its ability to bring single-stranded DNA molecules together and resembles SSB in its ability to reduce secondary structure in single-stranded DNA.

Homologous pairing between nucleosome cores on a linear duplex DNA and nucleoprotein filaments of RecA protein-single stranded DNA

The ability of E coli recA protein to promote homologous pairing with linear duplex DNA bound to HU protein (Nucleosome cores) was found to be differentially affected. The formation of paranemic joint molecules was not affected whereas the formation of plectomic joint molecules was inhibited from the start of the reaction. The formation of paranemic joint molecules between nucleoprotein filaments of recA protein-circular single stranded DNA and closed circular duplex DNA is believed to generate positive supercoiling in the duplex DNA. We found that the positively superhelical duplex DNA was inert in the formation of joint molecules but could be converted into an active substrate, in situ, by the action of wheat germ topoisomerase I. These observations initiate an understanding of the structural features of E coli chromosome such as DNA supercoiling and nucleosome-like structures in homologous recombination.

Convergence analysis of the Newton algorithm and a pseudo-time marching scheme for diffuse correlation tomography

We propose a self-regularized pseudo-time marching scheme to solve the ill-posed, nonlinear inverse problem associated with diffuse propagation of coherent light in a tissuelike object. In particular, in the context of diffuse correlation tomography (DCT), we consider the recovery of mechanical property distributions from partial and noisy boundary measurements of light intensity autocorrelation. We prove the existence of a minimizer for the Newton algorithm after establishing the existence of weak solutions for the forward equation of light amplitude autocorrelation and its Frechet derivative and adjoint. The asymptotic stability of the solution of the ordinary differential equation obtained through the introduction of the pseudo-time is also analyzed. We show that the asymptotic solution obtained through the pseudo-time marching converges to that optimal solution provided the Hessian of the forward equation is positive definite in the neighborhood of optimal solution. The superior noise tolerance and regularization-insensitive nature of pseudo-dynamic strategy are proved through numerical simulations in the context of both DCT and diffuse optical tomography. (C) 2010 Optical Society of America.

Deuterium-carbon correlation in static oriented systems using DAPT - A windowless multiple pulse sequence

We present a new method for establishing correlation between deuterium and its attached carbon in a deuterated liquid crystal. The method is based on transfer of polarization using the DAPT pulse sequence proposed originally for two spin half nuclei, now extended to a spin-1 and a spin-1/2 nuclei. DAPT utilizes the evolution of magnetization of the spin pair under two blocks of phase shifted BLEW-12 pulses on one of the spins separated by a 90 degree pulse on the other spin. The method is easy to implement and does not need to satisfy matching conditions unlike the Hartmann-Hahn cross-polarization. Experimental results presented demonstrate the efficacy of the method.

Correlation between conductivity or diffusivity and activation energy in amorphous solids

There exist many investigations of ionic transport in a variety of glasses. These studies exhibit strong correlation between ionic conductivity and activation energy: Typically, it is found that higher conductivity is associated with lower activation energies and vice versa. Although there are explanations for this at a phenomenological level, there is no consistent physical picture to explain the correlation between conductivity and activation energy. We have carried out molecular dynamics simulation as a function of the size of the impurity atom or diffusant (both neutral and charged) in a host amorphous matrix. We find that there is a maximum in self-diffusivity as a function of the size of the impurity atom suggesting that there is an appropriate size for which the diffusivity is maximum. The activation energy is found to be the lowest for this size of the impurity. A similar maximum has been previously found in other condensed phases, such as confined fluids and dense liquids, and has its origin in the levitation effect. The implications of this result for understanding ionic conductivity in glasses are discussed. Our results suggest that there is a relation between microscopic structure of the amorphous solid, diffusivity or conductivity, and activation energy. The nature of this relationship is discussed in terms of the levitation parameter showing that diffusivity is maximum when the size of the neck or doorway radius is comparable with the size of the diffusant. Our computational results here are in excellent agreement with independent experimental results of Nascimento et al. [Braz. J. Phys. 35, 626 (2005)] that structural features of the glass are important in determining the ionic conductivity.

Correlation, Coding, and Cooperation in Wireless Sensor Networks

We consider a single-hop data-gathering sensor network, consisting of a set of sensor nodes that transmit data periodically to a base-station. We are interested in maximizing the lifetime of this network. With our definition of network lifetime and the assumption that the radio transmission energy consumption forms the most significant portion of the total energy consumption at a sensor node, we attempt to enhance the network lifetime by reducing the transmission energy budget of sensor nodes by exploiting three system-level opportunities. We pose the problem of maximizing lifetime as a max-min optimization problem subject to the constraint of successful data collection and limited energy supply at each node. This turns out to be an extremely difficult optimization to solve. To reduce the complexity of this problem, we allow the sensor nodes and the base-station to interactively communicate with each other and employ instantaneous decoding at the base-station. The chief contribution of the paper is to show that the computational complexity of our problem is determined by the complex interplay of various system-level opportunities and challenges.

Low correlation sequences over AM-PSK and QAM alphabets

A construction for a family of sequences over the 8-ary AM-PSK constellation that has maximum nontrivial correlation magnitude bounded as theta(max) less than or similar to root N is presented here. The famfly is asymptotically optimal with respect to the Welch bound on maximum magnitude of correlation. The 8-ary AM-PSK constellation is a subset of the 16-QAM constellation. We also construct two families of sequences over 16-QAM with theta(max) less than or similar to root 2 root N. These families are constructed by interleaving sets of sequences. A construction for a famBy of low-correlation sequences over QAM alphabet of size 2(2m) is presented with maximum nontrivial normalized correlation parameter bounded above by less than or similar to a root N, where N is the period of the sequences in the family and where a ranges from 1.61 in the case of 16-QAM modulation to 2.76 for large m. When used in a CDMA setting, the family will permit each user to modulate the code sequence with 2m bits of data. Interestingly, the construction permits users on the reverse link of the CDMA channel to communicate using varying data rates by switching between sequence famflies; associated to different values of the parameter m. Other features of the sequence families are improved Euclidean distance between different data symbols in comparison with PSK signaling and compatibility of the QAM sequence families with sequences belonging to the large quaternary sequence families {S(p)}.

Testing against changing correlation

A test for time-varying correlation is developed within the framework of a dynamic conditional score (DCS) model for both Gaussian and Student t-distributions. The test may be interpreted as a Lagrange multiplier test and modified to allow for the estimation of models for time-varying volatility in the individual series. Unlike standard moment-based tests, the score-based test statistic includes information on the level of correlation under the null hypothesis and local power arguments indicate the benefits of doing so. A simulation study shows that the performance of the score-based test is strong relative to existing tests across a range of data generating processes. An application to the Hong Kong and South Korean equity markets shows that the new test reveals changes in correlation that are not detected by the standard moment-based test.