Chaos game representation walk model for the protein sequences

A new chaos game representation of protein sequences based on the detailed hydrophobic--hydrophilic (HP) model has been proposed by Yu et al (Physica A 337 (2004) 171). A CGR-walk model is proposed based on the new CGR coordinates for the protein sequences from complete genomes in the present paper. The new CGR coordinates based on the detailed HP model are converted into a time series, and a long-memory ARFIMA(p, d, q) model is introduced into the protein sequence analysis. This model is applied to simulating real CGR-walk sequence data of twelve protein sequences. Remarkably long-range correlations are uncovered in the data and the results obtained from these models are reasonably consistent with those available from the ARFIMA(p, d, q) model.     

QSAR for RNases and theoretic–experimental study of molecular diversity on peptide mass fingerprints of a new <Emphasis Type="Italic">Leishmania infantum</Emphasis> protein

The toxicity and low success of current treatments for Leishmaniosis determines the search of new peptide drugs and/or molecular targets in Leishmania pathogen species (L. infantum and L. major). For example, Ribonucleases (RNases) are enzymes relevant to several biologic processes; then, theoretical and experimental study of the molecular diversity of Peptide Mass Fingerprints (PMFs) of RNases is useful for drug design. This study introduces a methodology that combines QSAR models, 2D-Electrophoresis (2D-E), MALDI-TOF Mass Spectroscopy (MS), BLAST alignment, and Molecular Dynamics (MD) to explore PMFs of RNases. We illustrate this approach by investigating for the first time the PMFs of a new protein of L. infantum. Here we report and compare new versus old predictive models for RNases based on Topological Indices (TIs) of Markov Pseudo-Folding Lattices. These group of indices called Pseudo-folding Lattice 2D-TIs include: Spectral moments π _k (x,y), Mean Electrostatic potentials ξ _k (x,y), and Entropy measures θ _k (x,y). The accuracy of the models (training/cross-validation) was as follows: ξ _k (x,y)-model (96.0%/91.7%)>π _k (x,y)-model (84.7/83.3) > θ _k (x,y)-model (66.0/66.7). We also carried out a 2D-E analysis of biological samples of L. infantum promastigotes focusing on a 2D-E gel spot of one unknown protein with M<20, 100 and pI <7. MASCOT search identified 20 proteins with Mowse score >30, but not one >52 (threshold value), the higher value of 42 was for a probable DNA-directed RNA polymerase. However, we determined experimentally the sequence of more than 140 peptides. We used QSAR models to predict RNase scores for these peptides and BLAST alignment to confirm some results. We also calculated 3D-folding TIs based on MD experiments and compared 2D versus 3D-TIs on molecular phylogenetic analysis of the molecular diversity of these peptides. This combined strategy may be of interest in drug development or target identification.     

In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis Dihydrofolate reductase,a potential target for anti-TB drug discovery

The worldwide TB structural genomics initiative has identified several new drug targets for Mycobacterium tuberculosis (M. tb). Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate that is essential for DNA synthesis. Inhibition of its activity leads to arrest of DNA synthesis and hence cell death. Thus, M. tb DHFR (mtDHFR) is an attractive novel drug target for developing anti-TB drugs. Structural comparison of mtDHFR and human DHFR (hDHFR) reveals key differences in the active sites. These differences can be exploited for the design of selective inhibitors for mtDHFR. Based on the recently determined high resolution crystal structure of mtDHFR complexed with known inhibitor methotrexate (MTX) and cofactor NADPH, a tri-peptide inhibitor has been identified using a structure-based drug design approach. Docking studies indicate that the designed tripeptide inhibitor has a high potency (K _d = 1.78 nM) and is a selective (approximately 120 fold over hDHFR) inhibitor for mtDHFR. Hence, the tripeptide is a suitable lead compound for the development of novel anti-TB drugs.     

Poisson–Lie T-Duality¶for Quasitriangular Lie Bialgebras

We introduce a new 2-parameter family of sigma models exhibiting Poisson–Lie T-duality on a quasitriangular Poisson–Lie group G. The models contain previously known models as well as a new 1-parameter line of models having the novel feature that the Lagrangian takes the simple form , where the generalised metric E is constant (not dependent on the field u as in previous models). We characterise these models in terms of a global conserved G-invariance. The models on G=SU ₂ and its dual G ^* are computed explicitly. The general theory of Poisson–Lie T-duality is also extended, notably the reduction of the Hamiltonian formulation to constant loops as integrable motion on the group manifold. The approach also points in principle to the extension of T-duality in the Hamiltonian formulation to group factorisations D=G⋈M, where the subgroups need not be dual or connected to the Drinfeld double. Received: 22 August 1999 / Accepted: 4 February 2000     

Theory of the thermal magnetocapacitance of multicomponent silicate glasses at low temperature

An explanation is put forward for the early findings of Zeller and Pohl (, Phys. Rev. B, 4, 2029) and, in particular, Stephens (, Phys. Rev. B, 13, 852), and then for the more comprehensive recent findings of Meißner and Strehlow () for the anomalous magnetic-field-dependent behaviour of the heat capacity of some multicomponent glasses at low temperature (0.1?<?T?<?4?K) and in weak-to-moderate fields (0?<?B?<?8T). An essential new ingredient of this theory, together with the standard two-level system approach for cold glasses, is a multi-minima local potential for the quantum motion of metallic ions between near-degenerate wells, separated by relatively shallow barriers. Taking the tunneling entities as independent and assuming a novel probability distribution for the parameters of the multi-welled potential, an expression for the heat capacity C(T,B) is obtained with features that match rather well the reported unusual experimental data for the glasses. The indication coming from this theory for the data available is that the entities involved in tunnelling are nanoclusters of coherent ions.     

Magnetic resonance imaging of rigid polymers at elevated temperatures with SPRITE

Magnetic resonance imaging has rarely been applied to rigid polymeric materials, due primarily to the strong dipolar coupling and short signal lifetimes inherent in these materials. SPRITE (single point ramped imaging withT ₁ enhancement) (B. J. Balcom, R. P. MacGregor, S. D. Beyea, D. P. Green, R. L. Armstrong, T. W. Bremner: J. Magn. Reson. A123, 131–134, 1996) is particularly well suited to imaging solid materials. With SPRITE, the only requirement is thatT ₂^* be long enough so that the signal can be phase-encoded. The minimum phase encoding time is limited by the maximum gradient strength available and by the instrument deadtime. At present this is usually tens of microseconds and will only improve with refinements in technology. We have used the SPRITE sequence in conjunction with raising the sample temperature to obtain images of rigid polymers that have largely frustrated conventional imaging methods. This approach provides a straightforward and reliable method for imaging a class of samples that, up until now, have been very difficult to image.     

Measurements of L subshell and L shell x‐ray fluorescence cross‐sections for U and Th

The Ll, Lα_{1, 2}, Lη, Lβ₆, Lβ_{2, 4, 15, 17}, Lβ_{1, 3, 5}, Lβ_{9, 10}, Lγ₁, Lγ_{2, 3, 6, 8}, Lγ_4,4′ and Lγ₅ x‐ray fluorescence cross‐sections for U and Th were measured at 59.5 keV incident photon energy by using theoretical L_i subshell photoelectric cross‐sections, fluorescence and Coster–Kronig yields and fractional emission rates, and calculated theoretically by using atomic parameters. The measured values were compared with the theoretical values and experimental results available in the literature. Copyright © 2003 John Wiley & Sons, Ltd.     

Evolutionary Accessibility in Tunably Rugged Fitness Landscapes

The adaptive evolution of a population under the influence of mutation and selection is strongly influenced by the structure of the underlying fitness landscape, which encodes the interactions between mutations at different genetic loci. Theoretical studies of such landscapes have been carried out for several decades, but only recently experimental fitness measurements encompassing all possible combinations of small sets of mutations have become available. The empirical studies have spawned new questions about the accessibility of optimal genotypes under natural selection. Depending on population dynamic parameters such as mutation rate and population size, evolutionary accessibility can be quantified through the statistics of accessible mutational pathways (along which fitness increases monotonically), or through the study of the basin of attraction of the optimal genotype under greedy (steepest ascent) dynamics. Here we investigate these two measures of accessibility in the framework of Kauffman’s LK-model, a paradigmatic family of random fitness landscapes with tunable ruggedness. The key parameter governing the strength of genetic interactions is the number K of interaction partners of each of the L sites in the genotype sequence. In general, accessibility increases with increasing genotype dimensionality L and decreases with increasing number of interactions K. Remarkably, however, we find that some measures of accessibility behave non-monotonically as a function of K, indicating a special role of the most sparsely connected, non-trivial cases K=1 and 2. The relation between models for fitness landscapes and spin glasses is also addressed.     

Targeted mutagenesis of the Sap47 gene of Drosophila: Flies lacking the synapse associated protein of 47 kDa are viable and fertile

Background  

Conserved proteins preferentially expressed in synaptic terminals of the nervous system are likely to play a significant role in brain function. We have previously identified and molecularly characterized the Sap47 gene which codes for a novel synapse associated protein of 47 kDa in Drosophila. Sequence comparison identifies homologous proteins in numerous species including C. elegans, fish, mouse and human. First hints as to the function of this novel protein family can be obtained by generating mutants for the Sap47 gene in Drosophila.     

Excitation functions and isomeric ratios in the reaction130Te (α,xpyn) for α-particle energies between 15 and 37 MeV

The¹³⁰Te(,n)¹³³Xe,¹³⁰Te(,p)¹³³I,¹³⁰Te(,pn)¹³²I and¹³⁰Te(, n)¹²⁹Te excitation functions for alpha particle energies between 14.7 and 36.5 MeV are presented. Excitation functions for the last three reactions are measured for the first time and more consistent results for (, n) are obtained. The isomeric ratios for the ( n), (, pn) and (, n) reactions were deduced. Calculations based on different theoretical models of equilibrium and preequilibrium decay are compared with the experimental results and discussed. Acceptable presentation of the energy behavior of the measured isomeric ratios was obtained when higher angular momentum depletion for preequilibrium emitted particles was included. The absolute values of the isomeric ratios however remain overestimated.We want to express our gratitude to Prof. Ts. Vylov and Dr. V. Brudanin (Dubna) who supplied us with measurement equipment, to Dr. Chr. Necheva for taking part in the experiments, to the U-200 cyclotron staff and to the direction of the Laboratory of Nuclear Reactions (JINR) for making the irradiation possible and to Dr. E. Dobreva (Sofia) for fruitful discussion of the experimental method. We wish to express our gratitude also to Prof. M. Uhl and the NEA data bank for making the computer code STAPRE available to us and to Prof. J. Ernst (Bonn) for fruitful discussions. This project has been completed with the financial support of the Committee for Science at the Council of Ministers under contract No. 644.     

Randomness and a step-like distribution of pile heights in avalanche models

This paper considers a one-parameter family of sand-piles. The family exhibits the crossover between the models with deterministic and stochastic relaxation. The mean pile height is used to describe the crossover. The height densities corresponding to the models with relaxation of both types approach one another as the parameter increases. Relaxation is supposed to deal with the local losses of grains by a fixed amount. In that case the densities show a step-like behaviour in contrast to the peaked shape found in the models with the local loss of grains down to a fixed level [S. Lübeck, Phys. Rev. E 62, 6149 (2000)]. A spectral approach based on the long-run properties of the pile height considers the models with deterministic and random relaxation more accurately and distinguishes between the two cases for admissible parameter values.     

Excited states of Ne isoelectronic ions: SAC-CI study

Excited states of the s, p, and d symmetries up to principal quantum number n = 4 are studied for the first eight members of Ne isoelectronic sequence (Ne to Cl⁷⁺) by the SAC-CI (symmetry-adapted-cluster configuration-interaction) method. The valence STO basis sets of Clementi et al. and the optimized excited STO are used by the STO-6G expansion method. The calculated transition energies agree well with the experimental values wherever available. Received 26 July 2000 and Received in final form 14 September 2000     

Self-interstitial configuration in molybdenum studied by modified analytical embedded atom method

The stability of various atomic configurations containing a self-interstitial atom (SIA) in a model representing Mo has been investigated using the modified analytical embedded atom method (MAEAM). The lattice relaxations are treated with the molecular dynamics (MD) simulation at absolute zero of temperature. Six relatively stable self-interstitial configurations and formation energies have been described and calculated. The results indicate that the [111] dumbbell interstitial S₁₁₁ has the lowest formation energy, and in ascending order, the sequence of the configurations is predicted to be S₁₁₁, C, S₁₁₀, T, S₀₀₁ and O. From relaxed displacement field up to the fifth-NN atoms of six configurations, we know that the relaxed displacements depend not only on separation distances of the NN atoms from the defect centre but also strongly on the direction of the connected line between the NN atoms and the defect centre. The equilibrium distances between two nearest atoms in the core of the S₁₁₁, C, S₁₁₀, T, S₀₀₁ and O configurations are 0.72a, 0.72a, 0.71a, 0.72a, 0.70a and 0.70a, respectively.      

Quantum Ergodicity for Graphs Related to Interval Maps

We prove quantum ergodicity for a family of graphs that are obtained from ergodic one-dimensional maps of an interval using a procedure introduced by Pakónski et al (J. Phys. A, 34, 9303-9317 (2001)). As observables we take the L ² functions on the interval. The proof is based on the periodic orbit expansion of a majorant of the quantum variance. Specifically, given a one-dimensional, Lebesgue-measure-preserving map of an interval, we consider an increasingly refined sequence of partitions of the interval. To this sequence we associate a sequence of graphs, whose directed edges correspond to elements of the partitions and on which the classical dynamics approximates the Perron-Frobenius operator corresponding to the map. We show that, except possibly for subsequences of density 0, the eigenstates of the quantum graphs equidistribute in the limit of large graphs. For a smaller class of observables we also show that the Egorov property, a correspondence between classical and quantum evolution in the semiclassical limit, holds for the quantum graphs in question.     

Chargino-neutralino production inp\bar p-collisions for the left-right supersymmetric model

An extension of the Supersymmetric Standard Model to the supersymmetricSU(2) _L×SU(2) _R×U(1) _B–L model is considered. The gauge group contains a bidoublet and triplet Higgs field. We investigate the possibility of detecting chargino and neutralino production in -collisions atCDF, namely . A numerical analysis is performed for , tan 1 and a lower bound on the lightest supersymmetric particle (LSP) mass, GeV. Using conservative assumptions ofM _WR300 GeV andgg _Lg _R, we find the cross sections are: , and pb, and thus _L 24 _L at TeV. Cross sections are also given for larger values of the center of mass energy up to those available at the SSC. The results are compared with the prompt-lepton background of theW _{L, R} ^– decays from . Both decays for bosons show Jacobian peaks for (p _T150 GeV forM _WR) at =90°. Furthermore the chargino signature unlike the promptlepton background is symmetric under the Jacobian peak. We also exhibit the dependence of the angular distribution of the chargino on the c.m. angle forp _T40 GeV, 150 GeV at TeV.     

Inner-shell ionization ofZ=25–32 elements by 5-48 MeV32S ions

TheK-shell ionization cross sections of Mn, Ni, Cu, Zn and Ge under³²S bombardment have been measured in the energy range from 5 to 48 MeV. The cross sections are compared with available theories based on a direct Coulomb ionization mechanism and with the predictions of theK-vacancy sharing process. This last process can reasonably account for the measured cross sections at high bombarding energies. The energy shifts of theK - andK -lines and theK /K -intensity ratios have also been measured. This information is used to deduce the defect configuration of the atoms. The mechanisms responsible for the multiple vacancy production are discussed.     

Isotopic dependence of the nuclear charge radii and binding energies in the relativistic Hartree-Fock formalism

Relativistic nonlinear models based on the Hartree and Hartree-Fock approximations, including the σ, ω, π, and ρ mesons, are worked out to explore the behavior of the nuclear charge radii and the binding energies of several isotopic chains. We find a correlation between the magnitude of the anomalous kink effect (KE) in the Pb isotopic family and the compressibility modulus (K) of nuclear matter. The KE appears to be sensitive, in particular, to the mechanisms which control the K value. The influence of the symmetry energy on the Ca isotopic chain is also studied. The behavior of the charge radii of single-particle states for some special cases and its repercussion on the nuclear charge radius is analyzed. The effect of pairing correlations on the models improves considerably the quality of the results in both binding energy and KE.     

Letter: On Tilted Perfect Fluid Bianchi Type VI0 Self-Similar Models

We show that the tilted perfect fluid Bianchi VI₀ family of self-similar models found by Rosquist and Jantzen [K. Rosquist and R. T. Jantzen, Exact power law solutions of the Einstein equations, 1985 Phys. Lett. 107A 29–32] is the most general class of tilted self-similar models but the state parameter lies in the interval (6/5, 3/2). The model has a four dimensional stable manifold indicating the possibility that it may be future attractor, at least for the subclass of tilted Bianchi VI₀ models satisfying n =0 in which it belongs. In addition the angle of tilt is asymptotically significant at late times suggesting that for the above subclasses of models the tilt is asymptotically extreme.