bluuebunny/crossref_metadata_2025 huggingface dataset:
Compensatory Functions of Two Alkyl Hydroperoxide Reductases in the Oxidative Defense System ofLegionella pneumophila
Authors: LeBlanc Jason J. , Davidson Ross J. , Hoffman Paul S.
Published: August 2006

Legionella pneumophilaexpresses two catalase-peroxidase enzymes that exhibit strong peroxidatic but weak catalatic activities, suggesting that other enzymes participate in decomposition of hydrogen peroxide (H2O2). Comparative genomics revealed thatL. pneumophilaand its close relativeCoxiella burnetiieach contain two peroxide-scavenging alkyl hydroperoxide reductase (AhpC) systems: AhpC1, which is similar to theHelicobacter pyloriAhpC system, and AhpC2 AhpD (AhpC2D), which is similar to the AhpC AhpD system ofMycobacterium tuberculosis. To establish a catalatic function for these two systems, we expressedL. pneumophila ahpC1orahpC2in a catalase/peroxidase mutant ofEscherichia coliand demonstrated restoration of H2O2resistance by a disk diffusion assay.ahpC1::Km andahpC2D::Km chromosomal deletion mutants were two- to eightfold more sensitive to H2O2,tert-butyl hydroperoxide, cumene hydroperoxide, and paraquat than the wild-typeL. pneumophila, a phenotype that could be restored bytrans-complementation. Reciprocal strategies to construct double mutants were unsuccessful. Mutant strains were not enfeebled for growth in vitro or in a U937 cell infection model. Green fluorescence protein reporter assays revealed expression to be dependent on the stage of growth, withahpC1appearing after the exponential phase andahpC2appearing during early exponential phase. Quantitative real-time PCR showed thatahpC1mRNA levels were ∼7- to 10-fold higher thanahpC2DmRNA levels. However, expression ofahpC2Dwas significantly increased in theahpC1mutant, whereasahpC1expression was unchanged in theahpC2Dmutant. These results indicate that AhpC1 or AhpC2D (or both) provide an essential hydrogen peroxide-scavenging function toL. pneumophilaand that the compensatory activity of theahpC2Dsystem is most likely induced in response to oxidative stress.
Sensor Domains Encoded in
Bacillus anthracis
Virulence Plasmids Prevent Sporulation by Hijacking a Sporulation Sensor Histidine Kinase
Authors: White Andrea K. , Hoch James A. , Grynberg Marcin , Godzik Adam , Perego Marta
Published: August 2006

Anthrax toxin and capsule, determinants for successful infection by
Bacillus anthracis
, are encoded on the virulence plasmids pXO1 and pXO2, respectively. Each of these plasmids also encodes proteins that are highly homologous to the signal sensor domain of a chromosomally encoded major sporulation sensor histidine kinase (BA2291) in this organism.
B. anthracis
Sterne overexpressing the plasmid pXO2-61-encoded signal sensor domain exhibited a significant decrease in sporulation that was suppressed by the deletion of the BA2291 gene. Expression of the sensor domains from the pXO1-118 and pXO2-61 genes in
Bacillus subtilis
strains carrying the
B. anthracis
sporulation sensor kinase BA2291 gene resulted in BA2291-dependent inhibition of sporulation. These results indicate that sporulation sensor kinase BA2291 is converted from an activator to an inhibitor of sporulation in its native host by the virulence plasmid-encoded signal sensor domains. We speculate that activation of these signal sensor domains contributes to the initiation of
B. anthracis
sporulation in the bloodstream of its infected host, a salient characteristic in the virulence of this organism, and provides an additional role for the virulence plasmids in anthrax pathogenesis.
Control of the
Streptomyces
Subtilisin Inhibitor Gene by AdpA in the A-Factor Regulatory Cascade in
Streptomyces griseus
Authors: Hirano Setsu , Kato Jun-ya , Ohnishi Yasuo , Horinouchi Sueharu
Published: August 2006

AdpA in the A-factor regulatory cascade in
Streptomyces griseus
activates a number of genes required for secondary metabolism and morphological differentiation, forming an AdpA regulon. The
Streptomyces
subtilisin inhibitor (SSI) gene,
sgiA
, in
S. griseus
was transcribed in response to AdpA, showing that
sgiA
is a member of the AdpA regulon. AdpA bound a single site upstream of the
sgiA
promoter at approximately position −70 with respect to its transcriptional start point. Mutational analysis of the AdpA-binding site showed that the AdpA-binding site was essential for transcriptional activation. Mutants in which
sgiA
was disrupted had higher trypsin, chymotrypsin, metalloendopeptidase, and total protease activities than the wild-type strain, which showed that SgiA modulated the activities of these extracellularly produced proteases. Because a number of genes encoding chymotrypsins, trypsins, and metalloendopeptidases, most of which are SSI-sensitive proteases, are also under the control of AdpA, the A-factor regulatory cascade was thought to play a crucial role in modulating the extracellular protease activities by triggering simultaneous production of the proteases and their inhibitor at a specific timing during growth. Mutants in which
sgiA
was disrupted grew normally and formed aerial hyphae and spores with the same time course as the wild-type strain. However, exogenous addition of purified SgiA to substrate mycelium grown on agar medium resulted in a delay in aerial mycelium formation, indicating that SgiA is involved in aerial hypha formation in conjunction with proteases.
Transposon Mutagenesis Identifies Genes Associated with
Mycoplasma pneumoniae
Gliding Motility
Authors: Hasselbring Benjamin M. , Page Clinton A. , Sheppard Edward S. , Krause Duncan C.
Published: August 2006

The wall-less prokaryote
Mycoplasma pneumoniae
, a common cause of chronic respiratory tract infections in humans, is considered to be among the smallest and simplest known cells capable of self-replication, yet it has a complex architecture with a novel cytoskeleton and a differentiated terminal organelle that function in adherence, cell division, and gliding motility. Recent findings have begun to elucidate the hierarchy of protein interactions required for terminal organelle assembly, but the engineering of its gliding machinery is largely unknown. In the current study, we assessed gliding in cytadherence mutants lacking terminal organelle proteins B, C, P1, and HMW1. Furthermore, we screened over 3,500
M. pneumoniae
transposon mutants individually to identify genes associated with gliding but dispensable for cytadherence. Forty-seven transformants having motility defects were characterized further, with transposon insertions mapping to 32 different open reading frames widely distributed throughout the
M. pneumoniae
genome; 30 of these were dispensable for cytadherence. We confirmed the clonality of selected transformants by Southern blot hybridization and PCR analysis and characterized satellite growth and gliding by microcinematography. For some mutants, satellite growth was absent or developed more slowly than that of the wild type. Others produced lawn-like growth largely devoid of typical microcolonies, while still others had a dull, asymmetrical leading edge or a filamentous appearance of colony spreading. All mutants exhibited substantially reduced gliding velocities and/or frequencies. These findings significantly expand our understanding of the complexity of
M. pneumoniae
gliding and the identity of possible elements of the gliding machinery, providing a foundation for a detailed analysis of the engineering and regulation of motility in this unusual prokaryote.
Crowding and Confinement Effects on Protein Diffusion In Vivo
Authors: Konopka Michael C. , Shkel Irina A. , Cayley Scott , Record M. Thomas , Weisshaar James C.
Published: August 2006

The first in vivo measurements of a protein diffusion coefficient versus cytoplasmic biopolymer volume fraction are presented. Fluorescence recovery after photobleaching yields the effective diffusion coefficient on a 1-μm-length scale of green fluorescent protein within the cytoplasm of
Escherichia coli
grown in rich medium. Resuspension into hyperosmotic buffer lacking K
+
and nutrients extracts cytoplasmic water, systematically increasing mean biopolymer volume fraction, <φ>, and thus the severity of possible crowding, binding, and confinement effects. For resuspension in isosmotic buffer (osmotic upshift, or Δ, of 0), the mean diffusion coefficient, <
D
>, in cytoplasm (6.1 ± 2.4 μm
2
s
−1
) is only 0.07 of the in vitro value (87 μm
2
s
−1
); the relative dispersion among cells, σ

D

/<
D
> (standard deviation, σ

D

, relative to the mean), is 0.39. Both <
D
> and σ

D

/<
D
> remain remarkably constant over the range of Δ values of 0 to 0.28 osmolal. For a Δ value of ≥0.28 osmolal, formation of visible plasmolysis spaces (VPSs) coincides with the onset of a rapid decrease in <
D
> by a factor of 380 over the range of Δ values of 0.28 to 0.70 osmolal and a substantial increase in σ

D

/<
D
>. Individual values of
D
vary by a factor of 9 × 10
4
but correlate well with
f
VPS
, the fractional change in cytoplasmic volume on VPS formation. The analysis reveals two levels of dispersion in
D
among cells: moderate dispersion at low Δ values for cells lacking a VPS, perhaps related to variation in φ or biopolymer organization during the cell cycle, and stronger dispersion at high Δ values related to variation in
f
VPS
. Crowding effects alone cannot explain the data, nor do these data alone distinguish crowding from possible binding or confinement effects within a cytoplasmic meshwork.
Preparation and Conformational Study of B-Ring Substituted Lupane Derivatives
Authors: Dračínský Martin , Hybelbauerová Simona , Sejbal Jan , Buděšínský Miloš
Published: August 2006

New lupane-type triterpenoids with 5(6) double bond were prepared using the method of partial demethylation on carbon C-4. Hydroboration of the double bond led to 6α-hydroxy derivative. By the oxidation and following reduction of 6α-hydroxy derivative the 6-oxo and 6β-hydroxy derivatives were prepared. A new method for selective oxidation of secondary hydroxy group in the presence of primary hydroxy group was performed. The conformation of ring A of new lupane-type 3-oxo derivatives with a substituent on ring B was elucidated on the bases of 1H and 13C NMR spectra and molecular modelling.
Synthesis and Structure Assignment of 2-(4-Methoxybenzyl)cyclohexyl β-D-Galactopyranoside Stereoisomers
Authors: Šaman David , Wimmerová Martina , Wimmer Zdeněk
Published: August 2006

Several promoters were used in the Koenigs-Knorr synthesis of the title alkyl β-D-galactopyranosides, both in their diastereoisomeric forms (5a/5b and 6a/6b), resulting from the synthesis performed with the respective racemic cis and trans isomers of 2-(4-methoxybenzyl)cyclohexan-1-ol, and in their enantiomerically pure forms 5a and 6a, starting only from the (1S,2S)- and (1S,2R)-enantiomers of 2-(4-methoxybenzyl)cyclohexan-1-ol. The aim of the study was to find convenient modification(s) of the Koenigs-Knorr synthesis of alkyl β-D-galactopyranosides from more hindered and more complex 2-substituted cycloalkanols. Separation of the diastereoisomeric compounds using HPLC on a chiral Nucleodex-β-OH column was used to obtain small quantities of all possibly existing enantiomerically pure products for unambiguous structure assignment by NMR analysis. The (1S,2S)- and (1S,2R)- enantiomers of 2-(4-methoxybenzyl)cyclohexan-1-ol (1a and 2a) were prepared by a reduction of 2-(4-methoxybenzyl)cyclohexan-1-one with Saccharomyces cerevisiae in enantiomeric purities: ee = 98.5% ((1S,2S)-enantiomer (1a)), and ee ≥ 99% ((1S,2R)-enantiomer (2a)).
A New Stereocontrolled Approach to a Key Intermediate in the Synthesis of (2S,3R)-Capreomycidine
Authors: Martinková Miroslava , Gonda Jozef , Džoganová Martina
Published: August 2006

A new stereocontrolled approach to the synthesis of advanced intermediate in the synthesis of nonproteinogenic amino acid (2S,3R)-capreomycidine via the novel domino reaction has been developed.
Polymeric Conjugates of 9-[2-(Phosphonomethoxy)ethyl]purine with Potential Antiviral and Cytostatic Activity
Authors: Pechar Michal , Braunová Alena , Šubr Vladimír , Ulbrich Karel , Holý Antonín
Published: August 2006

Syntheses and characterization of polymer conjugates of 9-[2-(phosphonomethoxy)ethyl] (PME) derivatives of adenine (PMEA), 2,6-diaminopurine (PMEDAP) and guanine (PMEG) are described. The phosphonate group of these acyclic nucleotide analogues was activated by reaction with triphenylphosphine and di(2-pyridyl) disulfide (TPP-PDS). The activated phosphonate reacted with a random copolymer containing N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-methacrylamidopropanoyl)ethane-1,2-diamine (Ma-AP-ED) units. The phosphonamide bond between the nucleotide and polymer carrier proved to be relatively stable at physiological pH 7.4 while at pH 5.0 (corresponding to endosomal or lysosomal compartments of cells) underwent slow hydrolysis. The rate of hydrolysis (drug release) was shown to depend on the detailed structure of the heterocyclic base. The polymer-drug conjugates described in the paper represent a new family of antiviral and cytostatic drugs with potentially improved pharmacokinetics, sustained drug release and diminished non-specific toxicity.
Reliable change assessment with practice effects in sport concussion research: a comment on Hinton-Bayre
Authors: Maassen G H , Bossema E R , Brand N
Published: August 2006

In his comments on our previous article, Hinton-Bayre advocates the use of the regression based approach in most cases of determining reliable change. This article comments on Hinton-Bayre’s argument, discusses cases where the regression method might not be the preferred method, and presents adjustments that make the method more generally preferable.
ENERGY DISTRIBUTION IN THE DYADOSPHERE OF A REISSNER–NORDSTRÖM BLACK HOLE IN MØLLER'S PRESCRIPTION
Authors: VAGENAS ELIAS C.
Published: August 2006

The energy and momentum distributions in the dyadosphere of a Reissner–Nordström black hole are evaluated. The Møller's energy-momentum complex is employed for this computation. The spacetime under study is modified due to the effects of vacuum fluctuations in the dyadosphere. Therefore, the corrected Reissner–Nordström black hole metric takes into account the first contribution of the weak field limit of one-loop QED. Furthermore, a comparison and a consequent connection between our results and those already existing in the literature is provided. We hypothesize that when the energy distribution is of specific form there is a relation that connects the coefficients in the Einstein's prescription with those in the Møller's prescription.
NEUTRINO MASS AND LEPTON NUMBER VIOLATION IN THE LITTLE HIGGS MODEL
Authors: GOYAL ASHOK
Published: August 2006

We study lepton number violation in little Higgs model and find that the choice of putting triplet Higgs vev equal to zero so as not to have any tree level neutrino Majorana mass is not natural in the sense that such a term is generated at the one-loop level. We investigate the contribution of exotic lepton number violating terms on neutrinoless double beta decay, K meson decay and on trilepton production in ν–N scattering.
FOCUS POINTS AND THE LIGHTEST HIGGS BOSON MASS IN THE MINIMAL SUPERSYMMETRIC STANDARD MODEL
Authors: JURČIŠINOVÁ E. , JURČIŠIN M.
Published: August 2006

We investigate the focus points of the renormalization group equations of the minimal supersymmetric standard model. We show that within this model the up- and down-type Higgs mass soft supersymmetry breaking parameters have focus point behavior at the electroweak scale simultaneously when appropriate conditions are fulfilled. The focus point scenario holds for large tan β. This two-focus-point scenario allows to fix the pole top-quark mass which is within the experimentally allowed interval. The main goal of this paper is the investigation of the influence of the existence of focus points on the determination of the mass of the lightest Higgs boson.
ISOLATED LEPTONS IN EVENTS WITH LARGE MISSING TRANSVERSE MOMENTUM AND THE SEARCH FOR SINGLE TOP PRODUCTION AT HERA
Authors: FERRANDO J.
Published: August 2006

Recent results in searches for high transverse momentum leptons in events with large missing transverse momentum in electron–proton collisions at HERA are reviewed. These searches have implications for searches for physics beyond the Standard Model. The most recent results on searches for single top production via Flavour Changing Neutral Currents are reviewed. The consistency of results from the H1 and ZEUS collaborations and prospects of discovering new physics during the final year of HERA running are discussed.
A SIMPLE TOY MODEL FOR EFFECTIVE RESTORATION OF CHIRAL SYMMETRY IN EXCITED HADRONS
Authors: COHEN THOMAS D. , GLOZMAN LEONID YA.
Published: August 2006

A simple solvable toy model exhibiting effective restoration of chiral symmetry in excited hadrons is constructed. A salient feature is that while physics of the low-lying states is crucially determined by the spontaneous breaking of chiral symmetry, in the high-lying states the effects of chiral symmetry breaking represent only a small correction. Asymptotically the states approach the regime where their properties are determined by the underlying unbroken chiral symmetry.
COHERENT SYNCHRONIZATION IN LINEARLY COUPLED NONLINEAR SYSTEMS
Authors: ZHOU TIANSHOU , CHEN GUANRONG
Published: August 2006

This paper presents a novel result on the effect of coupling through both analytical and numerical investigations on linearly coupled systems including chaotic and nonchaotic systems. It is found that when a single system has potential of oscillation but is currently in a "marginal" state to produce a limit cycle via Hopf bifurcation due to the change of a parameter, an appropriate coupling strength can excite the potential limit cycle such that the coupled system oscillates synchronously. Similarly, when a stable limit cycle is at the "margin" of a chaotic attractor in a single system, a certain coupling strength can induce the potential chaotic attractor such that the coupled system has a synchronous chaotic behavior. This excitation mechanism is different from the traditional function of coupling in that the latter mainly drives the coupled system to synchronize with the ongoing dynamics of a single system but does not recover its disappearing dynamics. This newly observed synchronization is called coherent synchronization to distinguish it from various common types of synchronization. Several numerical examples are presented for quantitative description of this interesting phenomenon.
REALIZATION OF BOOLEAN FUNCTIONS VIA CNN WITH VON NEUMANN NEIGHBORHOODS
Authors: CHEN FANGYUE , HE GUOLONG , CHEN GUANRONG
Published: August 2006

Recently, an effective method for realizing linearly separable Boolean functions via Cellular Neural Networks (CNN), called the threshold bifurcation method, was introduced, with a CNN gene bank of four variables established [Chen & Chen, 2005]. Based on this success, the present paper is to further explore the realization of all linearly separable Boolean functions of five variables via CNN with von Neumann neighborhoods. This paper provides: (i) important and essential relations among the genes (or templates) and the offsets of an uncoupled CNN as well as the basis of the binary input vectors set, (ii) a neat truth table of uncoupled CNN with five input variables, (iii) 94572 linearly separable Boolean functions (LSBF) in the family of 225 = 4.294967296 × 109 Boolean functions of five variables, realizable by a single CNN, and (iv) all 94572 CNN linearly separable Boolean genes (LSBG), which can be determined to form the CNN gene bank of five variables.
GENERATION OF SYMMETRICAL COLORED IMAGES VIA SOLUTION OF THE INVERSE PROBLEM OF CHEMICAL REACTIONS DISCRETE CHAOTIC DYNAMICS
Authors: GONTAR V. , GRECHKO O.
Published: August 2006

An automatic procedure for generating colored two-dimensional symmetrical images based on the chemical reactions discrete chaotic dynamics (CRDCD) is proposed. The inverse problem of derivation of symmetrical images from CRDCD mathematical models was formulated and solved using a special type of genetic algorithm. Different symmetrical images corresponding to the solutions of a CRDCD mathematical model for which the parameters were obtained automatically by the proposed method are presented.
SYNCHRONIZATION OF UNCERTAIN CHAOTIC SYSTEMS BASED ON THE FUZZY-MODEL-BASED APPROACH
Authors: LAM H. K. , LEUNG F. H. F.
Published: August 2006

This paper investigates the synchronization of chaotic systems subject to parameter uncertainties. Based on the fuzzy-model-based approach, a switching controller will be proposed to deal with the synchronization problem. The stability conditions will be derived based on the Lyapunov approach. The tracking performance and parameter design of the proposed switching controller will be formulated as a generalized eigenvalue minimization problem which can be solved numerically using some convex programming techniques. Simulation examples will be given to show the effectiveness of the proposed approach.
SYNCHRONIZATION OF CHAOTIC SYSTEMS WITH PARAMETRIC UNCERTAINTY AND MISMATCH
Authors: WEN C. Y. , JI Y. , SOH Y. C. , LI Z. G.
Published: August 2006

In this paper, we present two new schemes to synchronize a driven chaotic system with the driving chaotic system in the presence of parametric uncertainties and parametric mismatch between the two systems. A controller is designed for the driven system based on the bounds of the uncertainties. Sufficient conditions are derived to ensure synchronization of the two systems. Numerical results also show the robustness and effectiveness of the proposed schemes.
A NEWTON METHOD FOR LOCATING INVARIANT TORI OF MAPS
Authors: DANKOWICZ HARRY , THAKUR GUNJAN
Published: August 2006

This paper presents an iterative method for locating invariant tori of maps. Specifically, through the introduction of a shift function on the torus corresponding to the projection of the dynamics on the torus onto toral parameters, a discrete system of equations may be formulated whose solution approximates the spatial location of the torus. As invariant tori of continuous flows may be considered invariant under the application of the flow for a fixed time, or may correspond to invariant tori (of one less dimension) of suitably introduced Poincaré maps, the methodology applies to discrete and continuous dynamical systems alike. Moreover, the insensitivity of the method to the local stability characteristics of the invariant torus as well as to the precise nature of the flow on the torus imply, for example, that the method can be employed for the continuation of unstable invariant tori on which the dynamics are attracted to a periodic trajectory as long as the torus is sufficiently smooth. The proposed methodology as well as reduced formulations that result from a priori knowledge about the invariant torus are illustrated through some sample dynamical systems.
LOCALIZATION OF RESPONSE FUNCTIONS OF SPIRAL WAVES IN THE FITZHUGH–NAGUMO SYSTEM
Authors: BIKTASHEVA I. V. , HOLDEN A. V. , BIKTASHEV V. N.
Published: August 2006

Dynamics of spiral waves in perturbed, e.g. slightly inhomogeneous or subject to a small periodic external force, two-dimensional autowave media can be described asymptotically in terms of Aristotelean dynamics, so that the velocities of the spiral wave drift in space and time are proportional to the forces caused by the perturbation. The forces are defined as a convolution of the perturbation with the spirals Response Functions, which are eigenfunctions of the adjoint linearized problem. In this paper we find numerically the Response Functions of a spiral wave solution in the classic excitable FitzHugh–Nagumo model, and show that they are effectively localized in the vicinity of the spiral core.
PATTERNS OF EXACT SYNCHRONIZATION IN CHAINS OF FEEDBACK LOOPS WITH TWO CHARACTERISTIC TIME-LAGS
Authors: BURIĆ NIKOLA , TODOROVIĆ KRISTINA , VASOVIĆ NEBOJŠA
Published: August 2006

Synchronization patterns in chains of N bi-directionally delayed coupled systems with delayed feedback are studied. Each system is hyperchaotic when decoupled from the chain. It is shown that chains with odd or even number of cites N display different spatial patterns of stable exact synchronization. When N is odd the only stable pattern of exact synchronization is between all of the units. When N is even, next to the nearest neighbors could become exactly synchronized, with the dynamics of the nearest neighbors related in a more complicated way. Sufficiently strong coupling leads to the nearest neighbor synchronization also for even N. No other patterns have been observed.
CHAOS INDUCEMENT AND ENHANCEMENT IN TWO PARTICULAR NONLINEAR MAPS USING WEAK PERIODIC/QUASIPERIODIC PERTURBATIONS
Authors: ZHANG JIE , SMALL MICHAEL , ZHANG KAI
Published: August 2006

Weak periodic perturbation has long been used to suppress chaos in dynamical systems. In this paper, however, we demonstrate that weak periodic or quasiperiodic perturbation can also be used to induce chaos in nonchaotic parameter ranges of chaotic maps, or to enhance the already existing chaotic state. Two kinds of chaotic maps, the period doubling system and the Hopf bifurcation system, are employed as basic models to analyze and compare in detail the different mechanisms of inducing and enhancing chaos in them. In addition, a special kind of intermittency characterized by its periodicity is found for the first time in periodically perturbed Henon map, and reasonable speculations are presented to explain its complicated dynamics.
ON THE PERIODICITY OF AN IMPLICIT DIFFERENCE EQUATION WITH DISCONTINUITY: ANALYSIS AND SIMULATIONS
Authors: XU JIAN-XIN , PAN YA-JUN , YAN RUI , ZHANG WEINIAN
Published: August 2006

In this note we analyze the periodicity of an implicit nonlinear difference equation subject to perturbations and discontinuity. We prove the existence of multiple periodic solutions under certain conditions, and derive the periods which are functions of the sampling period and the period of the perturbation. In this work, we further present a simulation algorithm which enables the computation of the solution for the implicit difference equation in an iterative manner. The Van der Pol circuit is used as an illustrative example.
A NONLINEAR DYNAMICS PERSPECTIVE OF WOLFRAM'S NEW KIND OF SCIENCE PART VI: FROM TIME-REVERSIBLE ATTRACTORS TO THE ARROW OF TIME
Authors: CHUA LEON O. , SBITNEV VALERY I. , YOON SOOK
Published: August 2006

This paper proves, via an analytical approach, that 170 (out of 256) Boolean CA rules in a one-dimensional cellular automata (CA) are time-reversible in a generalized sense. The dynamics on each attractor of a time-reversible rule N is exactly mirrored, in both space and time, by its bilateral twin ruleN†. In particular, all 69 period-1 rules, 17 (out of 25) period-2 rules, and 84 (out of 112) Bernoulli rules are time-reversible.

The remaining 86 CA rules are time-irreversible in the sense that N and N† mirror their dynamics only in space, but not in time. In this case, each attractor of N defines a unique arrow of time.

A simple "time-reversal test" is given for testing whether an attractor of a CA rule is time-reversible or time-irreversible. For a time-reversible attractor of a CA rule N the past can be uniquely recovered from the future of N†, and vice versa. This remarkable property provides 170 concrete examples of CA time machines where time travel can be routinely achieved by merely hopping from one attractor to its bilateral twin attractor, and vice versa. Moreover, the time-reversal property of some local rules can be programmed to mimic the matter–antimatter "annihilation" or "pair-production" phenomenon from high-energy physics, as well as to mimic the "contraction" or "expansion" scenarios associated with the Big Bang from cosmology.

Unlike the conventional laws of physics, which are based on a unique universe, most CA rules have multiple universes (i.e. attractors), each blessed with its own laws. Moreover, some CA rules are endowed with both time-reversible attractors and time-irreversible attractors.

Using an analytical approach, the time-τ return map of each Bernoulli στ-shift attractor of all 112 Bernoulli rules are shown to obey an ultra-compact formula in closed form, namely,.

[Formula: see text]

or its inverse map.

These maps completely characterize the time-asymptotic (steady state) behavior of the nonlinear dynamics on the attractors. In-depth analysis of all but 18 global equivalence classes of CA rules have been derived, along with their basins of attraction, which characterize their transient regimes.

Above all, this paper provides a rigorous nonlinear dynamics foundation for a paradigm shift from an empirical-based approach à la Wolfram to an attractor-based analytical theory of cellular automata.
CONSERVATIVE AND NON-CONSERVATIVE BOLTZMANN-TYPE MODELS OF SEMICONDUCTOR THEORY
Authors: ARLOTTI L. , BANASIAK J. , CIAKE CIAKE F. L.
Published: August 2006

In this paper we analyze the linear Boltzmann equation of semiconductor theory with unbounded collision term modelling both elastic and inelastic scattering of electrons on the crystalline lattice (corresponding to scattering on impurities and optical phonons), in both bounded and unbounded domains. We prove the existence of a substochastic semigroup solving this problem and, for a large class of scattering cross-sections, we also characterize the generator of this semigroup as the closure of the formal right-hand side operator showing thus that the semigroup is conservative (stochastic) in this case. On the other hand, we provide an example of a cross-section growing at an exponential rate for which the semigroup is not conservative.
EULER EQUATIONS WITH SEVERAL INDEPENDENT PRESSURE LAWS AND ENTROPY SATISFYING EXPLICIT PROJECTION SCHEMES
Authors: CHALONS CHRISTOPHE , COQUEL FRÉDÉRIC
Published: August 2006

This work aims at numerically approximating the entropy weak solutions of Euler-like systems asymptotically recovered from the multi-pressure Navier–Stokes equations in the regime of an infinite Reynolds number. The nonconservation form of the limit PDE model makes the shock solutions to be sensitive with respect to the underlying small scales. Here we propose to model these small scale effects via a set of generalized jump conditions expressed in terms of the independent internal energies. The interest in considering internal energies stems from the presence of solely first-order nonconservative products by contrast to other variables. These nonconservative products are defined in the now classical sense proposed by Dal Maso, LeFloch and Murat. We show how to enforce the generalized jump conditions at the discrete level with a fairly simple numerical procedure. This method is proved to satisfy a full set of stability estimates and to produce approximate solutions in good agreement with exact Riemann solutions.
L1 STABILITY FOR THE VLASOV–POISSON–BOLTZMANN SYSTEM AROUND VACUUM
Authors: DUAN RENJUN , ZHANG MEI , ZHU CHANGJIANG
Published: August 2006

Based on the global existence theory of the Vlasov–Poisson–Boltzmann system around vacuum in the N-dimensional phase space, in this paper, we prove the uniform L1 stability of classical solutions for small initial data when N ≥ 4. In particular, we show that the stability can be established directly for the soft potentials, while for the hard potentials and hard sphere model it is obtained through the construction of some nonlinear functionals. These functionals thus generalize those constructed by Ha for the case without force to capture the effect of the force term on the time evolution of solutions. In addition, the local-in-time L1 stability is also obtained for the case of N = 3.
ON THE CONTINUITY OF THE RESPONSE MAP AND AN ALTERNATIVE SHOOTING METHOD FOR THE HALF-SPACE GINZBURG–LANDAU MODEL
Authors: BOLLEY CATHERINE , HELFFER BERNARD
Published: August 2006

As a consequence of a rather complete analysis of the qualitative properties of the solutions of the Ginzburg–Landau equations, we prove, in this paper, both the continuity of a fundamental map σ, called response map in the physical literature on superconductors, and the convergence of an efficient algorithm for the computation of the graph of σ. The response map σ gives the intensity h of the external magnetic field for which the Ginzburg–Landau equations (in a half-space) have a solution such that the parameter order has a prescribed value at the boundary of the sample. Our study involves a shooting method on either one or the other unknown of the system; our algorithm has been introduced in Bolley–Helffer for small values of the Ginzburg–Landau parameter κ and extended in Bolley to any value of κ. Our preceding mathematical studies were not sufficient to prove the convergence, but a recent result (in Ref. 3) on the monotonicity of the solutions with respect to h, combined with a more extensive use of the properties of the solutions of the Ginzburg–Landau system, allow us to complete the proof and to get, as a by-product, the continuity of σ.
Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes
Authors: Okuno Masaaki , Minami Kohtaro , Okumachi Akinori , Miyawaki Kazumasa , Yokoi Norihide , Toyokuni Shinya , Seino Susumu
Published: August 2006

We recently found that pancreatic acinar cells isolated from normal adult mouse can transdifferentiate into insulin-secreting cells in vitro. Using two different animal models of type 1 diabetes, we show here that insulin-secreting cells can also be generated from pancreatic acinar cells of rodents in the diabetic state with absolute insulin deficiency. When pancreatic acinar cells of streptozotocin-treated mice were cultured in suspension in the presence of epidermal growth factor and nicotinamide under low-serum condition, expressions of insulin genes gradually increased. In addition, expressions of other pancreatic hormones, including glucagon, somatostatin, and pancreatic polypeptide, were also induced. Analysis by the Cre/loxP-based direct cell lineage tracing system revealed that these newly made cells originated from amylase-expressing pancreatic acinar cells. Insulin secretion from the newly made cells was significantly stimulated by high glucose and other secretagogues. In addition, insulin-secreting cells were generated from pancreatic acinar cells of Komeda diabetes-prone rats, another animal model of type 1 diabetes. The present study demonstrates that insulin-secreting cells can be generated by transdifferentiation from pancreatic acinar cells of rodents in the diabetic state and further suggests that pancreatic acinar cells represent a potential source of autologous transplantable insulin-secreting cells for treatment of type 1 diabetes.
Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene
Authors: Kang Jung-Hoon , Kim Myung-Jun , Jang Hwa-In , Koh Kyung-Hee , Yum Keun-Sang , Rhie Duck-Joo , Yoon Shin Hee , Hahn Sang June , Kim Myung-Suk , Jo Yang-Hyeok
Published: August 2006

Glucagon-like peptide-1 and its potent agonist exendin-4 induce several immediate early response genes (IEGs) that code for transcription factors implicated in cell proliferation, differentiation, and apoptosis. We recently observed that early growth response factor-1 (EGR-1), an IEG product, was required for transcriptional activation of Ccnd1 ( cyclin D1) gene by exendin-4. Herein, the regulatory mechanism whereby exendin-4 activates the transcription of EGR-1 gene was investigated in the pancreatic β-cell line INS-1. Deletion analysis of rat EGR-1 promoter identified a critical region between −73 and −46 for the activation of EGR-1 in response to exendin-4. Mutation of the proximal putative cAMP response element (CRE, 5′-GTACGTCA-3′) located at −69 resulted in a significant decrease in the EGR-1 transcription, whereas the mutation of the distal putative CRE at −139 was without such an effect. In immune supershift assays using exendin-4-treated cells, binding of cAMP response element-binding protein (CREB) phosphorylated on Ser133 to the proximal CRE was increased. Employment of a CREB mutant containing Ala substitution at Ser133 or a dominant negative CREB mutant that inhibits the binding of endogenous CREB to DNA significantly decreased the exendin-4-induced EGR-1 transcription. In experiments using specific protein kinase inhibitors, the effect of H-89 was more prominent than PD-98059, indicating the predominance of the PKA signaling over the MEK/ERK in induction of EGR-1. Therefore, it appears that the proximal CRE site is critical and the binding with CREB phosphorylated on Ser133 is necessary for induction of the EGR-1 transcription by exendin-4.
T222P mutation of the insulin-like 3 hormone receptor LGR8 is associated with testicular maldescent and hinders receptor expression on the cell surface membrane
Authors: Bogatcheva Natalia V. , Ferlin Alberto , Feng Shu , Truong Anne , Gianesello Lisa , Foresta Carlo , Agoulnik Alexander I.
Published: August 2006

Insulin-like 3 (INSL3) hormone plays a crucial role in testicular descent during embryonic development. Genetic ablation of Insl3 or its G protein-coupled receptor (GPCR) Lgr8 causes cryptorchidism in mice. Previously, we identified a nonfunctional T222P mutation of LGR8 in several human patients with testicular maldescent. Using a large population of patients and healthy controls from Italy, we have demonstrated that T222P LGR8 mutation is present only in affected patients (19 T222P/+ of 598 vs. 0/450, P < 0.0001). We have also identified a novel allele of LGR8 (R223K) found in one patient with retractile testes. Both mutations are located in the leucine-rich repeats (LRRs) of GPCR ectodomain. The expression analysis of T222P mutant receptor transfected into 293T cells revealed that the mutation severely compromised GPCR cell membrane expression. The substitution of Thr222 with the neutral Ser or Ala, or the R223K mutation, did not alter receptor cell membrane expression or ligand-induced cAMP increase. Additional mutations, affecting first leucine in a signature LxxLxLxxN/CxL stretch of LRR (L283F), or the amino acid residues, forming the disulfide bond or coordinating calcium ion in the LDLa module (C71Y and D70Y), also rendered proteins with reduced cell surface expression. The structural alterations of both LRRs and LDLa of the ligand-binding part of LGR8 cause the inability of receptor to express on the cell surface membrane and might be responsible for the abnormal testicular phenotype in patients.
The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise
Authors: Sahlin K. , Mogensen M. , Bagger M. , Fernström M. , Pedersen P. K.
Published: August 2006

The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (V̇o2 peak60.7 ± 1.6, n = 8) and untrained subjects (39.5 ± 2.0 ml·min−1·kg−1, n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49–93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I ( r = 0.62, P = 0.03), but was not different between trained (62 ± 5%) and untrained subjects (72 ± 2%). MFO was correlated to RER during submaximal exercise at 80 ( r = −0.62, P = 0.02) and 120 W ( r = −0.71, P = 0.007) and interpolated 35% V̇o2 peak( r = −0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.
Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins
Authors: Lumeng Carey N. , Deyoung Stephanie M. , Saltiel Alan R.
Published: August 2006

Obesity leads to a proinflammatory state with immune responses that include infiltration of adipose tissue with macrophages. These macrophages are believed to alter insulin sensitivity in adipocytes, but the mechanisms that underlie this effect have not been characterized. We have explored the interaction between macrophages and adipocytes in the context of both indirect and direct coculture. Macrophage-secreted factors blocked insulin action in adipocytes via downregulation of GLUT4 and IRS-1, leading to a decrease in Akt phosphorylation and impaired insulin-stimulated GLUT4 translocation to the plasma membrane. GLUT1 was upregulated with a concomitant increase in basal glucose uptake. These changes recapitulate those seen in adipose tissue from insulin-resistant humans and animal models. TNF-α-neutralizing antibodies partially reversed the insulin resistance produced by macrophage-conditioned media. Peritoneal macrophages and macrophage-enriched stromal vascular cells from adipose tissue also attenuated responsiveness to insulin in a manner correlating with inflammatory cytokine secretion. Adipose tissue macrophages from obese mice have an F4/80+CD11b+CD68+CD14− phenotype and form long cellular extensions in culture. Peritoneal macrophages take on similar characteristics in direct coculture with adipocytes and induce proinflammatory cytokines, suggesting that macrophage activation state is influenced by contact with adipocytes. Thus both indirect/secreted and direct/cell contact-mediated factors derived from macrophages influence insulin sensitivity in adipocytes.
Cellular colocalization and coregulation between hypothalamic pro-TRH and prohormone convertases in hypothyroidism
Authors: Espinosa Veronica Paez , Ferrini Monica , Shen Xiaoxiong , Lutfy Kabirullah , Nillni Eduardo A. , Friedman Theodore C.
Published: August 2006

The prohormone convertases (PCs), PC1/3 and PC2, are involved in the tissue-specific endoproteolytic posttranslational processing of many hormonal precursors within the secretory pathway. One important prohormone, pro-thyrotropin-releasing hormone (TRH), is expressed in both hypophysiotropic (where it regulates the secretion of thyroid-stimulating hormone) and nonhypophysiotropic regions of the brain. Pro-TRH is processed at specific sites in the secretory pathway, primarily by PC1/3 followed by PC2. We hypothesized that thyroid hormone status in specific nuclei of the brain would alter pro-TRH processing by inducing changes in PC1/3 and PC2 expression. Therefore, we examined pro-TRH, PC1/3, and PC2 coexpression and coregulation in the paraventricular nucleus (PVN), lateral hypothalamus (LH), and ventromedial nucleus (VMN) of hypothyroid and euthyroid rats. Our results show that 6- n-propyl-2-thiouracil (PTU) treatment producing hypothyroidism induced a significant increase in the expression of PC1/3, PC2, and pro-TRH in the PVN and LH, but not VMN. When confocal studies were performed, an increase in colocalization of PC1/3 or PC2 in pro-TRH was observed only in PVN, a response that was especially prominent in the ventral and medial areas of the PVN. PTU did not regulate colocalization in the VMH or LH. Regulation of colocalization of processing enzyme and prohormone expression is a novel mechanism to alter hormonal biosynthesis.
Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice
Authors: Thomson D. M. , Porter B. B. , Tall J. H. , Kim H-J. , Barrow J. R. , Winder W. W.
Published: August 2006

LKB1 has been identified as a component of the major upstream kinase of AMP-activated protein kinase (AMPK) in skeletal muscle. To investigate the roles of LKB1 in skeletal muscle, we used muscle-specific LKB1 knockout (MLKB1KO) mice that exhibit low expression of LKB1 in heart and skeletal muscle, but not in other tissues. The importance of LKB1 in muscle physiology was demonstrated by the observation that electrical stimulation of the muscle in situ increased AMPK phosphorylation and activity in the wild-type (WT) but not in the muscle-specific LKB1KO mice. Likewise, phosphorylation of acetyl-CoA carboxylase (ACC) was markedly attenuated in the KO mice. The LKB1KO mice had difficulty running on the treadmill and exhibited marked reduction in distance run in voluntary running wheels over a 3-wk period (5.9 ± 0.9 km/day for WT vs. 1.7 ± 0.7 km/day for MLKB1KO mice). The MLKB1KO mice anesthetized at rest exhibited significantly decreased phospho-AMPK and phospho-ACC compared with WT mice. KO mice exhibited lower levels of mitochondrial protein expression in the red and white regions of the quadriceps. These observations, along with previous observations from other laboratories, clearly demonstrate that LKB1 is the major upstream kinase in skeletal muscle and that it is essential for maintaining mitochondrial marker proteins in skeletal muscle. These data provide evidence for a critical role of LKB1 in muscle physiology, one of which is maintaining basal levels of mitochondrial oxidative enzymes. Capacity for voluntary running is compromised with muscle and heart LKB1 deficiency.
Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/Pi IIa transporter to thetrans-Golgi
Authors: Lanaspa Miguel A. , Giral Héctor , Breusegem Sophia Y. , Halaihel Nabil , Baile Goretti , Catalán Julia , Carrodeguas José A. , Barry Nicholas P. , Levi Moshe , Sorribas Víctor
Published: August 2006

The function of the NaPiIIa renal sodium-phosphate transporter is regulated through a complex network of interacting proteins. Several PDZ domain-containing proteins interact with its COOH terminus while the small membrane protein MAP17 interacts with its NH2end. To elucidate the function of MAP17, we identified its interacting proteins using both bacterial and mammalian two-hybrid systems. Several PDZ domain-containing proteins, including the four NHERF proteins, as well as NaPiIIa and NHE3, were found to bind to MAP17. The interactions of MAP17 with the NHERF proteins and with NaPiIIa were further analyzed in opossum kidney (OK) cells. Expression of MAP17 alone had no effect on the NaPiIIa apical membrane distribution, but coexpression of MAP17 and NHERF3 or NHERF4 induced internalization of NaPiIIa, MAP17, and the PDZ protein to the trans-Golgi network (TGN). This effect was not observed when MAP17 was cotransfected with NHERF1/2 proteins. Inhibition of protein kinase C (PKC) prevented expression of the three proteins in the TGN. Activation of PKC in OK cells transfected only with MAP17 induced complete degradation of MAP17 and NaPiIIa. When lysosomal degradation was prevented, both proteins accumulated in the TGN. When the dopamine D1-like receptor was activated with fenoldopam, both NaPiIIa and MAP17 also accumulated in the TGN. Finally, cotransfection of MAP17 and NHERF3 prevented the adaptive upregulation of phosphate transport activity in OK cells in response to low extracellular phosphate. Therefore, the interaction between MAP17, NHERF3/4, and NaPiIIa in the TGN could be an important intermediate or alternate path in the internalization of NaPiIIa.