bluuebunny/crossref_metadata_2025 huggingface dataset:
Λ-INFLATION AND CMB ANISOTROPY
Authors: LUKASH V. N. , MIKHEEVA E. V.
Published: August 2004

We explore a broad class of three-parameter inflationary models of the very early Universe, called the Λ-inflation, and its observational predictions: high abundance of cosmic gravitational waves consistent with the Harrison–Zel'dovich spectrum of primordial cosmological perturbations, the non-power-law winglike spectrum of matter density perturbations, and others. High efficiency of these models to meet observational tests is briefly discussed. We show that a parity contribution of the gravitational waves and adiabatic density perturbations into the large-scale temperature anisotropy, T/S~1, is a common feature of Λ-inflation; the maximum values of T/S (basically not larger than 10) are reached in models where (i) the local spectrum shape of density perturbations is flat or slightly red (nS≲1), and (ii) the residual potential energy of the inflaton is near the GUT scale [Formula: see text]. The conditions to get large T/S in the inflationary paradigm and the relation of T/S to the ratio of the power spectra, r, and to the inflationary γ and Hubble parameters, are discussed. We argue that a simple estimate, [Formula: see text], is valid for most known inflationary solutions and allows to relate straightforwardly the important parameters of observational and physical cosmology.
DIFFERENCE EQUATIONS FOR THE HIGHER RANK XXZ MODEL WITH A BOUNDARY
Authors: KOJIMA TAKEO , QUANO YAS-HIRO
Published: August 2004

The higher rank analog of the XXZ model with a boundary is considered on the basis of the vertex operator approach. We derive difference equations of the quantum Knizhnik–Zamolodchikov type for 2N-point correlations of the model. We present infinite product formulae of two point functions with free boundary condition by solving those difference equations with N=1.
THE MICROSCOPIC WORLD UNVEILED BY ELECTRON WAVES
Authors: TONOMURA AKIRA
Published: August 2004

Electron interference has been investigated at an industrial laboratory of Hitachi, Ltd. for the past 30 years thanks to the encouragement and support of C. N. Yang, who retired from the State University of New York in 1999. This paper reports here fundamentals and applications of electron interference experiments we have carried out including our relation to C. N. Yang, and is based on a talk made in honor of him at the "Symmetries and Reflections" Symposium held at Stony Brook in May 1999.
CLOSED N=2 STRINGS: PICTURE-CHANGING, HIDDEN SYMMETRIES AND SDG HIERARCHY
Authors: LECHTENFELD OLAF , POPOV ALEXANDER D.
Published: August 2004

We study the action of picture-changing and spectral flow operators on a ground ring of ghost number zero operators in the chiral BRST cohomology of the closed N=2 string and describe an infinite set of symmetry charges acting on physical states. The transformations of physical string states are compared with symmetries of self-dual gravity which is the effective field theory of the closed N=2 string. We derive all infinitesimal symmetries of the self-dual gravity equations in (2+2)-dimensional space–time and introduce an infinite hierarchy of commuting flows on the moduli space of self-dual metrics. The dependence on moduli parameters can be recovered by solving the equations of the SDG hierarchy associated with an infinite set of Abelian symmetries generated recursively from translations. These nonlocal Abelian symmetries are shown to coincide with the hidden Abelian string symmetries responsible for the vanishing of most scattering amplitudes. Therefore, N=2 string theory "predicts" not only self-dual gravity but also the SDG hierarchy.
R-VALUES FROM LOW ENERGY e+e-ANNIHILATION
Authors: ZHAO ZHENGGUO
Published: August 2004

The QED running coupling constant α(s) and the anomalous magnetic moment of muon aμare two fundamental quantities for the precision test of the Standard Model (SM). The current uncertainties on α(s) and aμare dominated by the contribution from the R-values measured about 20 years ago with an averaged uncertainty of 15% in the energy region below 5 GeV. This review article summarizes the recent measurements of R-values in low energy e+e-annihilation. The new experiments aimed at reducing the uncertainties in R-values and performed with the upgraded Beijing Spectrometer (BESII) at Beijing Electron Positron Collider (BEPC) in Beijing and with Cryogenic Magnetic Detector, CMD-2 and SND (Spherical Neutral Detector) at VEEP-2M in Novosibirsk are reviewed and discussed.
LOCAL SYMMETRIES AND THE NOETHER IDENTITIES IN THE HAMILTONIAN FRAMEWORK
Authors: DERIGLAZOV A. A. , EVDOKIMOV K. E.
Published: August 2004

We study in the Hamiltonian framework the local transformations [Formula: see text] which leave invariant the Lagrangian action: δεS= div . Manifest form of the symmetry and the corresponding Noether identities is obtained in the first order formalism as well as in the Hamiltonian one. The identities have very simple form and interpretation in the Hamiltonian framework. Part of them allows one to express the symmetry generators which correspond to the primarily expressible velocities through the remaining one. The other part of the identities allows one to select subsystem of constraints with a special structure from the complete constraint system. It means, in particular, that the above written symmetry implies an appearance of the Hamiltonian constraints up to at least ([k]+1) stage. It is proven also that the Hamiltonian symmetries can always be presented in the form of canonical transformation for the phase space variables. The manifest form of the resulting generating function is obtained.
QUANTUM VERTEX OPERATORS FOR THE SINE–GORDON MODEL
Authors: SAVELIEV M. V. , ZUEVSKY A. B.
Published: August 2004

On the basis of the second Drinfeld realization of [Formula: see text] we construct the quantum version of vertex operators for the sine–Gordon model which are responsible for the generation of soliton solutions in the classics. The quantum vertex operators satisfy relations of Zamolodchikov algebra and possess the quantum interaction function. We discuss also their possible role in the quantum soliton theory.
HIDDEN NONLINEAR SUPERSYMMETRIES IN PURE PARABOSONIC SYSTEMS
Authors: PLYUSHCHAY MIKHAIL
Published: August 2004

The existence of intimate relations between generalized statistics and supersymmetry is established by the observation of hidden supersymmetric structure in pure parabosonic systems. This structure is characterized generally by a nonlinear superalgebra. The nonlinear supersymmetry of parabosonic systems may be realized, in turn, by modifying appropriately the usual supersymmetric quantum mechanics. The relation of nonlinear parabosonic supersymmetry to the Calogero-like models with exchange interaction and to the spin chain models with inverse-square interaction is pointed out.
NEUTRINO OSCILLATION IN WEITZENBÖCK SPACE–TIME
Authors: ZHANG C. M.
Published: August 2004

In the framework of the teleparallel equivalent of general relativity, we obtain the evolution equation of the neutrino oscillation in vacuum. A comparison with the equivalent result of general relativity case, shows that the Dirac equation in Riemann and Weitzenböck space–times is equivalent in the spherical symmetric Schwarzschild space–time, but turns out to be different in the case of the axial symmetry.
LATTICE GAUGE THEORIES AND THE AdS/CFT CORRESPONDENCE
Authors: CASELLE M.
Published: August 2004

This review is devoted to a comparison between lattice gauge theories and AdS/CFT results for the nonperturbative behavior of nonsupersymmetric Yang–Mills theories. It is intended for readers who are assumed not to be experts in LGT. For this reason the first part is devoted to a pedagogical introduction to the Lattice regularization of QCD. In the second part we discuss some basic features of the AdS/CFT correspondence and compare the results obtained in the nonsupersymmetric limit with those obtained on the lattice. We discuss in particular the behavior of the string tension and of the glueball spectrum.
TOPOLOGICAL REVERBERATIONS IN FLAT SPACE–TIMES
Authors: GOMERO G. I. , REBOUÇAS M. J. , TEIXEIRA A. F. F. , BERNUI A.
Published: August 2004

We study the role played by multiply-connectedness in the time evolution of the energy E(t) of a radiating system that lies in static flat space–time manifolds ℳ4 whose t= const spacelike sections ℳ3 are compact in at least one spatial direction. The radiation reaction equation of the radiating source is derived for the case where ℳ3 has any nontrivial flat topology, and an exact solution is obtained. We show that the behavior of the radiating energy E(t) changes remarkably from exponential damping, when the system lies in ℛ3, to a reverberation pattern (with discontinuities in the derivative Ė(t) and a set of relative minima and maxima) followed by a growth of E(t), when ℳ3 is endowed with any one of the 17 multiply-connected flat topologies. It emerges from this result that the compactness in at least one spatial direction of Minkowski space–time is sufficient to induce this type of topological reverberation, making clear that topological fragilities can arise not only in the usual cosmological modelling, but also in ordinary flat space–time manifolds. An explicit solution of the radiation reaction equation for the case where [Formula: see text] is discussed in detail, and graphs which reveal how the energy varies with the time are presented and analyzed.
A UNIFIED APPROACH TO EXTERNAL AND INTERNAL SYMMETRIES
Authors: WISNIVESKY DANIEL
Published: August 2004

We present a new approach to the question of a unified theory of external and internal symmetries based on the assumption that the physical world is a group manifold. We choose the parameters of the group as the basic elements from which to build the external and internal space coordinates. We define the wave function equation for a nonrelativistic charged particle and obtain, among other results, the quantization of electric charge.
GRAVITATIONAL LENSING AS FOLDS IN THE SKY
Authors: MOLLERACH SILVIA , ROULET ESTEBAN
Published: August 2004

We revisit the gravitational lensing phenomenon using a new visualization technique. It consists in projecting the observers sky into the source plane, what gives rise to a folded and stretched surface. This provides a clear graphical tool to visualize some interesting well-known effects, such as the development of multiple images of a source, the structure of the caustic curves, the parity of the images and their magnification as a function of the source position.
ENCKE METHODS ADAPTED TO REGULARIZING VARIABLES
Authors: VIGO-AGUIAR JESÚS , FERRÁNDIZ JOSÉ M. , SIMOS THEODORE E.
Published: August 2004

In this paper formulations of Encke's type corresponding to the best known sets of linearizing coordinates KS and BF are presented. They are easier to derive than the usual formulation in Cartesian variables, since no numerical difficulties appear in the equations of motion. The experiments performed show a remarkably good behavior of the new methods for the numerical integration of satellite orbits, the performance of the classic version being clearly improved, at least in the analyzed cases corresponding to nearly circular low Earth orbits. Some questions concerning the possibility of increasing the accuracy by means of rectifications are briefly treated. Moreover our methods are proved to be able to compete with the corresponding methods in linear KS or BF elements.
FRACTONS AND FRACTAL STATISTICS
Authors: DA CRUZ WELLINGTON
Published: August 2004

Fractons are anyons classified into equivalence classes and they obey specific fractal statistics. The equivalence classes are labeled by a fractal parameter or Hausdorff dimension h. We consider this approach in the context of the fractional quantum Hall effect (FQHE) and the concept of duality between such classes, defined by [Formula: see text] shows us that the filling factors for which the FQHE were observed just appear into these classes. A connection between equivalence classes h and the modular group for the quantum phase transitions of the FQHE is also obtained. A β-function is defined for a complex conductivity which embodies the classes h. The thermodynamics is also considered for a gas of fractons (h,ν) with a constant density of states and an exact equation of state is obtained at low-temperature and low-density limits. We also prove that the Farey sequences for rational numbers can be expressed in terms of the equivalence classes h.
QUANTUM ALGEBRA OF THE PARTICLE MOVING ON THE q-DEFORMED MASS-HYPERBOLOID
Authors: MORARIU BOGDAN
Published: August 2004

I introduce a reality structure on the Heisenberg double of Fun q( SL (N,C)) for q phase, which for N=2 can be interpreted as the quantum phase space of the particle on the q-deformed mass-hyperboloid. This construction is closely related to the q-deformation of the symmetric top. Finally, I conjecture that the above real form describes zero modes of certain noncompact WZNZ-models.
WHITHAM DEFORMATIONS OF SEIBERG–WITTEN CURVES FOR CLASSICAL GAUGE GROUPS
Authors: TAKASAKI KANEHISA
Published: August 2004

Gorsky et al. presented an explicit construction of Whitham deformations of the Seiberg–Witten curve for the [Formula: see text] SUSY Yang–Mills theory. We extend their result to all classical gauge groups and some other cases such as the spectral curve of the [Formula: see text] affine Toda system. Our construction, too, uses fractional powers of the superpotential W(x) that characterizes the curve. We also consider the u-plane integral of topologically twisted theories on four-dimensional manifolds X with [Formula: see text] in the language of these explicitly constructed Whitham deformations and an integrable hierarchy of the KdV type hidden behind.
THE ISGUR–WISE FUNCTION IN A QCD INSPIRED QUARK MODEL
Authors: CHOUDHURY D. K. , BORDOLOI NAMITA SHARMA
Published: August 2004

We summarize the results of the Isgur–Wise function investigated within a QCD inspired quark model. We estimate the slope and the convexity parameter of the function.
NEUTRINO OSCILLATIONS IN A 3νL+3νR FRAMEWORK WITH FIVE LIGHT NEUTRINOS
Authors: SUEMATSU DAIJIRO
Published: August 2004

We propose a neutrino mass matrix model in which five neutrino species remain light through the seesaw mechanism within a supersymmetric 3νL+3νR framework. We construct such a model based on the nonrenormalizable terms in the superpotential constrained by the discrete symmetry which may be expected in the models at the high energy scale such as superstring. We study the possible oscillation phenomena by fixing mass parameters so as to explain the solar and atmospheric neutrino deficits and also include a candidate of the suitable dark matter. We also discuss the charged lepton mass matrix based on this neutrino model. LSND results may be consistently explained within this model.
A DESIGN METHOD OF BURSTING USING TWO-PARAMETER BIFURCATION DIAGRAMS IN FITZHUGH–NAGUMO MODEL
Authors: TSUJI SHIGEKI , UETA TETSUSHI , KAWAKAMI HIROSHI , AIHARA KAZUYUKI
Published: August 2004

Spiking and bursting observed in nerve membranes seem to be important when we investigate information representation model in the brain. Many topologically different bursting responses are observed in the mathematical models and their related bifurcation mechanisms have been clarified. In this paper, we propose a design method to generate bursting responses in FitzHugh–Nagumo model with a simple periodic external force based on bifurcation analysis. Some effective parameter perturbations for the amplitude of the external input are given from the two-parameter bifurcation diagram.
LIFTED DIGITAL REDESIGN OF PREDICTION-BASED DIGITAL CONTROLLER FOR HYBRID CHAOTIC SYSTEM
Authors: WANG HSUN-PANG , TSAI JASON SHENG-HONG , YI YONG-IL , SHIEH LEANG-SAN
Published: August 2004

Tracking a periodic orbit of a chaotic attractor has been a considerable challenge since it often encounters numerical sensitivity. In this paper, a lifted prediction-based low-gain digital controller obtained from a predesigned high-gain analog controller is developed and applied to the hybrid chaotic system. The new proposed digital tracker with a relatively longer sampling time is insensitive to numerical errors and performs better than the one developed via the existing prediction-based digital redesign method. The Chen and Chua attractors are used as illustrative examples to demonstrate the effectiveness of the proposed lifted digital redesign method.
THE FORMATION OF VORONOI DIAGRAMS IN CHEMICAL AND PHYSICAL SYSTEMS: EXPERIMENTAL FINDINGS AND THEORETICAL MODELS
Authors: DE LACY COSTELLO BEN , RATCLIFFE NORMAN , ADAMATZKY ANDREW , ZANIN ALEXEY L. , LIEHR ANDREAS W. , PURWINS HANS-GEORG
Published: August 2004

The work discusses the formation of Voronoi diagrams in spatially extended nonlinear systems taking experimental and theoretical results into account. Concerning experimental systems a number of chemical systems used previously as prototype chemical processors and a barrier gas-discharge system are investigated. Although the underlying microscopic processes are very different, both types of systems show self-organized Voronoi diagrams for suitable parameters. Indeed certain chemical systems exhibit Voronoi diagrams as an output state for two distinct sets of parameters one that corresponds to the interaction of stable forced trigger waves and the other that corresponds to the spontaneous initiation and interaction of waves due to point instabilities in the system. In the case of the chemical systems front initiation, propagation and interaction (annihilation) are the primary mechanisms for Voronoi diagram formation, in the case of the barrier gas-discharge system regions of vanishing electric field define the medial axes of the Voronoi diagram. On the basis of cellular automata models the general concept of the formation of Voronoi diagrams has been explained, and related mechanisms have been simulated. Another intuitive approach towards the understanding of self-organized Voronoi diagrams has been given on the basis of reaction–diffusion models explaining the formation of Voronoi diagrams as a result of the mutual interactions of trigger fronts. The variety of systems exhibiting Voronoi diagrams as stationary states indicates that Voronoi diagrams are a generic and natural pattern formation phenomenon.
PIECEWISE TWO-DIMENSIONAL MAPS AND APPLICATIONS TO CELLULAR NEURAL NETWORKS
Authors: CHANG HSIN-MEI , JUANG JONG
Published: August 2004

Of concern is a two-dimensional map T of the form T(x,y)=(y,F(y)-bx). Here F is a three-piece linear map. In this paper, we first prove a theorem which states that a semiconjugate condition for T implies the existence of Smale horseshoe. Second, the theorem is applied to show the spatial chaos of one-dimensional Cellular Neural Networks. We improve a result of Hsu [2000].
GLOBAL SYNCHRONIZATION OF COUPLED DELAYED NEURAL NETWORKS AND APPLICATIONS TO CHAOTIC CNN MODELS
Authors: CHEN GUANRONG , ZHOU JIN , LIU ZENGRONG
Published: August 2004

This paper formulates the model and then studies its dynamics of a system of linearly and diffusively coupled identical delayed neural networks (DNNs), which is generalization of delayed Hopfied neural networks (DHNNs) and delayed cellular neural networks (DCNNs). In particularly, a simple yet generic sufficient condition for global synchronization of such coupled DNNs is derived based on the Lyapunov functional methods and Hermitian matrix theory. It is shown that global synchronization of coupled DNNs is ensured by a suitable design of the coupling matrix and the inner linking matrix. Furthermore, the result is applied to some typical chaotic neural networks. Finally, numerical simulations are presented to demonstrate the effectiveness of the approach.
EXACT COMPUTATION OF THE BIFURCATION POINT B4 OF THE LOGISTIC MAP AND THE BAILEY–BROADHURST CONJECTURES
Authors: KOTSIREAS I. S. , KARAMANOS K.
Published: August 2004

We compute explicitly the irreducible polynomial corresponding to the bifurcation point B4 of the logistic map. This settles in the positive recent two conjectures by Bailey and Broadhurst.
ROBUST CHAOS IN POLYNOMIAL UNIMODAL MAPS
Authors: PÉREZ GABRIEL
Published: August 2004

Simple polynomial unimodal maps which show robust chaos, that is, a unique chaotic attractor and no periodic windows in their bifurcation diagrams, are constructed. Their invariant distributions and Lyapunov exponents are examined.
LOOP GAIN AND ITS RELATION TO NONLINEAR BEHAVIOR AND CHAOS IN A TRANSFORMER-COUPLED OSCILLATOR
Authors: ZHANG JIANXIN , CHEN XIAODONG , DAVIES ANTHONY C.
Published: August 2004

A relationship between the loop gain and nonlinear behavior of a transformer-coupled oscillator is established in this paper. With increase of the loop gain, the system undergoes a series of changes in its dynamical behavior, i.e. no oscillation, near-sinusoidal, period-doubling, chaotic and squegging oscillations. It is expected that the approach of loop gain analysis can be universally applied to investigating the nonlinear behavior, especially chaos, in other oscillators.
DYNAMICS OF PIECEWISE LINEAR DISCONTINUOUS MAPS
Authors: KOLLÁR LÁSZLÓ E. , STÉPÁN GÁBOR , TURI JÁNOS
Published: August 2004

In this paper, the dynamics of maps representing classes of controlled sampled systems with backlash are examined. First, a bilinear one-dimensional map is considered, and the analysis shows that, depending on the value of the control parameter, all orbits originating in an attractive set are either periodic or dense on the attractor. Moreover, the dense orbits have sensitive dependence on initial data, but behave rather regularly, i.e. they have quasiperiodic subsequences and the Lyapunov exponent of every orbit is zero. The inclusion of a second parameter, the processing delay, in the model leads to a piecewise linear two-dimensional map. The dynamics of this map are studied using numerical simulations which indicate similar behavior as in the one-dimensional case.
STRUCTURED PSYCHOSOCIAL STRESS AND THERAPEUTIC FAILURE
Authors: WALLACE RODRICK , WALLACE DEBORAH
Published: August 2004

Generalized language-of-thought arguments, appropriate, in the sense of Dretske, to interacting cognitive modules, permit exploration of how disease states interact with medical treatment, given an embedding context of structured psychosocial stress. The interpenetrating feedback between treatment and response creates a kind of idiotypic hall of mirrors generating a synergistic pattern of efficacy, treatment failure, adverse reactions, and patient noncompliance which, from a Rate Distortion perspective, embodies a distorted image of externally-imposed structured stress. For the US, accelerating spatial and social spread of such stress enmeshes both dominant and subordinate populations in a linked system of pathogenic social hierarchy which will express itself, not only in an increasingly unhealthy society, but in the diffusion of therapeutic failure, including, but not limited to, drug-based treatments.
REGIONS OF RELATIVE GC% UNIFORMITY ARE RECOMBINATIONAL ISOLATORS
Authors: FORSDYKE D. R.
Published: August 2004

Among species within a phylogenetic group, genomic GC% values can cover a wide range that is particularly evident at third codon positions. However, among genes within a genome, genic GC% values can also cover a wide range that is, again, particularly evident at third codon positions. Individual genes and genomes each have a "homostabilizing propensity" to adopt a relatively uniform GC%. Each gene (a "microisochore") occupies a discrete GC% niche of relatively uniform base composition amongst its fellow genes, which can collectively span a wide GC% range. Homostabilization serves to recombinationally isolate both genome sectors (facilitating gene duplication and differentiation) and genomes (facilitating genome duplication and differentiation; e.g., speciation). Although they may sometimes be in conflict, the individualities of genomes, and of genes within those genomes, are separately sustained by a common mechanism, uniformity of GC%. The protection against inadvertent recombination afforded by GC% differentiation is, in the general case, a prerequisite for phenotypic differentiation.
HIV-1 POPULATION DYNAMICSIN VIVO: IMPLICATIONS FOR PATHOGENESIS, EFFECT OF CYTOKINE AND THERAPY STRATEGY
Authors: LOU JIE , MA ZHIEN , LOU MEIZHI , SHAO YIMING
Published: August 2004

In this paper, we present a dynamical model to study the spread of HIV-1 in vivo. Our goal is to better understand the interaction between HIV-1 and the human immune system. Making use of the Hill function, we describe two kinds of processions occurring in the immune response: the activation interactions or inhibitory interactions occurring between different components in the immune response, and the autocatalytic maintenance of the CD4+ T cells and CD8+ T cells populations. We also consider the impact of the cytokine interleukin-2 (IL-2) and the CD8 antiviral factor (CAF) on HIV-1 infection. Through numerical simulations we get several results. First, we find that the effects of IL-2 and CAF in the treatment for the infected are limiting. Namely, the curative effect will not always increase along with the dose of IL-2 or CAF or both. The increasing trend will stagnate at a certain dose that we used. Second, we find some possible reasons for the collapse of the lymph system in HIV-1 infection — the loss of these restraining functions, and/or the genetic variability of the virus due to immune escape that enhances the virulence, which then bring the collapse of the immune system. In some conditions the system will produce a Hopf bifurcation. We also simulate the theoretical warrant of the feasibility of the combined chemotherapy strategies for the HIV-1 infected patient.
NONLINEAR PROBIT GENE CLASSIFICATION USING MUTUAL INFORMATION AND WAVELET-BASED FEATURE SELECTION
Authors: ZHOU XIAOBO , WANG XIAODONG , DOUGHERTY EDWARD R.
Published: August 2004

We consider the problem of cancer classification from gene expression data. We propose using a mutual information-based gene or feature selection method where features are wavelet-based. The bootstrap technique is employed to obtain an accurate estimate of the mutual information. We then develop a nonlinear probit Bayesian classifier consisting of a linear term plus a nonlinear term, the parameters of which are estimated using the Gibbs sampler. These new methods are applied to analyze breast-cancer data and leukemia data. The results indicate that the proposed gene and feature selection method is very accurate in breast-cancer and leukemia classifications.
MODELING TUMOR CELL POPULATION DYNAMICS BASED ON MOLECULAR ADHESION ASSUMPTIONS
Authors: GRYGIERZEC WIESLAW , DEUTSCH ANDREAS , SCHUBERT WALTER , FRIEDENBERGER MANUELA , PHILIPSEN LARS
Published: August 2004

A model of cell population dynamics based on molecular adhesion is explained and discussed in this paper. We consider cancer cells experiencing interactions due to adhesion forces. In the cells' membranes there are proteins directly involved in adhesion. These proteins in the membrane are assembled in complex patterns called Combinatorial Protein Patterns (CPP). The goal of this work is to understand the mechanisms governing the adhesion process — in particular distinguishing CPPs involved in interactions. On the basis of experimental observation we have constructed an asynchronous cellular automaton (CA) model that simulates protein network dynamics in a population of cells.
Macrophage inflammatory protein-2 mediates the bowel injury induced by platelet-activating factor
Authors: Han Xin-Bing , Liu Xueli , Hsueh Wei , De Plaen Isabelle G.
Published: August 2004

Platelet-activating factor (PAF) is a potent endogenous mediator of bowel inflammation. It activates neutrophils that are needed to initiate the inflammatory response. Macrophage inflammatory protein-2 (MIP-2), a critical C-X-C chemokine secreted by macrophages and epithelial cells, is a potent chemoattractant for neutrophils. Whereas MIP-2 has been previously shown to mediate the injury in various organs, its role in acute intestinal injury has never been assessed. In this study, we first investigated the effect of PAF on MIP-2 expression in the intestine. Anesthetized young adult male Sprague-Dawley rats were injected intravenously with either PAF (1.5 μg/kg) or saline. Sixty minutes later, ileal MIP-2 gene expression was determined by semiquantitative RT-PCR, and plasma and ileal MIP-2 protein was determined by ELISA. In a second step, we assessed the role of MIP-2 in PAF-induced bowel injury. Rats were pretreated with rabbit anti-rat MIP-2 antibodies or control IgG for 90 min and then injected intravenously with PAF (2.5 μg/kg) for 90 min. We found that, in the rat intestine, 1) MIP-2 mRNA was only minimally expressed constitutively in sham-operated animals; 2) MIP-2 mRNA was significantly upregulated in response to PAF; 3) MIP-2 protein plasma levels and local production of MIP-2 in the ileum were markedly induced by PAF; 4) the administration of anti-rat MIP-2 IgG, but not control rabbit IgG, markedly reduced PAF-induced bowel injury (injury scores of 0.19 ± 0.09 vs. 1.12 ± 0.43, P < 0.05), hypotension, and leukopenia but did not reduce PAF-induced hemoconcentration. Thus we conclude that MIP-2 mediates PAF-induced intestinal injury.
αL-Integrin I domain cyclic peptide antagonist selectively inhibits T cell adhesion to pancreatic islet microvascular endothelium
Authors: Huang Meng , Matthews Kametra , Siahaan Teruna J. , Kevil Christopher G.
Published: August 2004

Insulitis is a hallmark feature of autoimmune diabetes that ultimately results in islet β-cell destruction. We examined integrin requirements and specific inhibition of integrin structure in T cell and monocyte adhesion to pancreatic islet endothelium. Examination of cell surface integrin expression on WEHI 7.1 T cells revealed prominent expression of β-, β1-, αL-integrins, and low expression of αM-integrins; whereas WEHI 274.1 monocytes showed significant staining for β2-, β1-, αM-molecules and no expression of αL-molecules. Unstimulated islet endothelium showed constitutive levels of ICAM-1 counter-ligand expression with minimal VCAM-1 expression; however, TNF-α stimulation increased cell surface density of both molecules. TNF-α increased T cell and monocyte rolling and adhesion under hydrodynamic flow conditions. Administration of a cyclic peptide competitor for the αL-integrin I domain binding sites (cyclo1,12-PenITDGEATDSGC) blocked T cell adhesion without inhibiting monocyte adhesion. Examination of T cell rolling revealed that cLAB.L treatment increased the average rolling velocity on activated endothelium and significantly decreased the fraction of T cells rolling at ≤50 μm/s, suggesting that cLAB.L treatment interferes with signal activation events required for the conversion of T cell rolling to firm adhesion. These data demonstrate for the first time that cyclic peptide antagonists against αL-integrin I domain attenuate T cell recruitment to islet endothelium.
Pressure activates rat pancreatic stellate cells
Authors: Watanabe Shiro , Nagashio Yoshikuni , Asaumi Hiroshi , Nomiyama Yoko , Taguchi Masashi , Tashiro Mitsuo , Kihara Yasuyuki , Nakamura Hayato , Otsuki Makoto
Published: August 2004

Pancreatic stellate cells (PSCs) play a central role in development of pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of the normal pancreas. We here evaluate the effects of pressure on the activation of rat PSCs. PSCs were isolated from the pancreas of Wistar rat using collagenase digestion and centrifugation with Nycodenz gradient. Pressure was applied to cultured rat PSCs by adding compressed helium gas into the pressure-loading apparatus to raise the internal pressure. Cell proliferation rate was assessed by 5-bromo-2′-deoxyuridine (BrdU) incorporation. MAPK protein levels and α-smooth muscle actin (α-SMA) expression were evaluated by Western blot analysis. Concentration of activated transforming growth factor-β1 (TGF-β1) secreted from PSCs into culture medium was determined by ELISA. Collagen type I mRNA expression and collagen secretion were assessed by quantitative PCR and Sirius red dye binding assay, respectively. Application of pressure significantly increased BrdU incorporation and α-SMA expression. In addition, pressure rapidly increased the phosphorylation of p44/42 and p38 MAPK. Treatment of PSCs with an MEK inhibitor and p38 MAPK inhibitor suppressed pressure-induced cell proliferation and α-SMA expression, respectively. Moreover, pressure significantly promoted activated TGF-β1 secretion, collagen type I mRNA expression, and collagen secretion. Our results demonstrate that pressure itself activates rat PSCs and suggest that increased pancreatic tissue pressure may accelerate the development of pancreatic fibrosis in chronic pancreatitis.
Disruption of smooth muscle gap junctions attenuates myogenic vasoconstriction of mesenteric resistance arteries
Authors: Earley Scott , Resta Thomas C. , Walker Benjimen R.
Published: August 2004

Communication between vascular smooth muscle (VSM) cells via low-resistance gap junctions may facilitate vascular function by synchronizing the contractile state of individual cells within the vessel wall. We hypothesized that inhibition of gap junctional communication would impair constrictor responses of mesenteric resistance arteries. Immunohistochemical experiments revealed positive staining for connexin 37 (Cx37) in both endothelium and smooth muscle of rat mesenteric arterioles, whereas connexin 43 (Cx43) immunoreactivity was not detected in the mesenteric vasculature. Administration of the gap junction inhibitory peptide Gap27, which targets Cx37 and Cx43, significantly diminished myogenic vasoconstriction (8.6 ± 3.8% of passive diameter at 100 Torr) and changes in vessel wall intracellular [Ca2+] of mesenteric resistance arteries compared with vessels treated with either vehicle (physiological saline solution) (33.5 ± 6.1%) or a control peptide (32.1 ± 6.5%). Administration of 18α-glycyrrhetinic acid, structurally distinct from Gap27, also significantly attenuated myogenic constriction compared with its vehicle control (DMSO) (9.6 ± 3.2% vs. 23.8 ± 4.6%). In contrast, phenylephrine-induced vasoconstriction was not altered by gap junction blockers. Attenuated myogenic vasoconstriction resulting from inhibition of gap junctions persisted after disruption of the endothelium. In additional experiments, VSM cell membrane potential was recorded in mesenteric resistance arteries pressurized to 20 or 100 Torr. VSM membrane potential was depolarized at 100 Torr compared with 20 Torr. However, VSM cells in arteries treated with Gap27 were significantly hyperpolarized (−48.6 ± 1.4 mV) at the higher pressure compared with vehicle (−41.4 ± 1.5 mV) and Gap20-treated (−38.4 ± 0.7 mV) vessels. Our findings suggest that inhibition of smooth muscle gap junctions attenuates pressure-induced VSM cell depolarization and myogenic vasoconstriction.
Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction
Authors: Song Ji , Cottler Patrick S. , Klibanov Alexander L. , Kaul Sanjiv , Price Richard J.
Published: August 2004

We showed previously that microbubble destruction with pulsed 1-MHz ultrasound creates a bioeffect that stimulates arteriogenesis and a chronic increase in hyperemia blood flow in normal rat muscle. Here we tested whether ultrasonic microbubble destruction can be used to create a microvascular remodeling response that restores hyperemia blood flow to rat skeletal muscle affected by arterial occlusion. Pulsed ultrasound (1 MHz) was applied to gracilis muscles in which the lateral feed artery was occluded but the medial feed artery was left intact. Control muscles were similarly occluded but did not receive ultrasound, microbubbles, or both. Hyperemia blood flow and number of smooth muscle (SM) α-actin-positive vessels, >30-μm arterioles, and capillaries per fiber were determined 7, 14, and 28 days after treatment. In ultrasound-microbubble-treated muscles, lateral region hyperemia blood flow was increased at all time points and restored to normal at day 28. The number of SM α-actin vessels per fiber was increased over control in this region at days 7 and 14 but decreased by day 28, when larger-diameter arterioles became more prevalent in the medial region. The number of capillaries per fiber was increased over control only at day 7 in the lateral region and only at days 7 and 14 in the medial region, indicating that the angiogenesis response was transient and likely did not contribute significantly to flow restoration at day 28. We conclude that ultrasonic microbubble destruction can be tailored to stimulate an arteriogenesis response that restores hyperemia blood flow to skeletal muscle in a rat model of arterial occlusion.
Deficiency of iNOS does not attenuate severe congestive heart failure in mice
Authors: Jones Steven P. , Greer James J. M. , Ware Paul D. , Yang Jiang , Walsh Kenneth , Lefer David J.
Published: August 2004

Inducible nitric oxide synthase (iNOS) has been implicated in the pathophysiology of congestive heart failure (CHF). Given the extensive evidence supporting this concept, we hypothesized that iNOS deficiency (iNOS−/−) would attenuate the severity of CHF in mice. Mice were subjected to permanent occlusion [myocardial infarction (MI)] of the proximal left anterior descending coronary artery to produce CHF. Cardiac function was assessed in vivo using echocardiography and ultraminiature ventricular pressure catheters. Sham wild-type ( n = 17), sham iNOS−/− ( n = 8), MI wild-type ( n = 56), and MI iNOS−/− ( n = 48) mice were subjected to MI (or sham MI) and followed for 1 mo. Deficiency of iNOS did not alter survival during CHF compared with wild type (35% vs. 32%, P = not significant). Furthermore, fractional shortening and cardiac output were not significantly different between wild-type (9.6 ± 2.0% and 441 ± 20 μl·min−1·g−1) and iNOS−/− (9.8 ± 1.3% and 471 ± 26 μl·min−1·g−1) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNOS−/− mice. None of the indexes demonstrated any significant differences between iNOS−/− and wild-type mice subjected to MI. These findings indicate that deficiency of iNOS does not significantly affect severe CHF in mice after MI.
Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterin
Authors: Blackwell Katherine A. , Sorenson Joseph P. , Richardson Darcy M. , Smith Leslie A. , Suda Osamu , Nath Karl , Katusic Zvonimir S.
Published: August 2004

Oxidative stress has been implicated as an important mechanism of vascular endothelial dysfunction induced by aging. Previous studies suggested that tetrahydrobiopterin (BH4), an essential cofactor of endothelial NO synthase, could be a molecular target for oxidation. We tested the hypothesis that oxidative stress, in particular oxidation of BH4, may contribute to attenuation of endothelium-dependent relaxation in aged mice. Vasomotor function of isolated carotid arteries was studied using a video dimension analyzer. Vascular levels of BH4and its oxidation products were measured via HPLC. In aged mice (age, 95 ± 2 wk), endothelium-dependent relaxation to ACh (10−5to 10−9M) as well as endothelium-independent relaxation to the NO donor diethylammonium ( Z)-1-( N, N-diethylamino)diazen-1-ium -1,2-diolate (DEA-NONOate, 10−5to 10−9M) were significantly reduced compared with relaxation detected in young mice (age, 23 ± 0.5 wk). Incubation of aged mouse carotid arteries with the cell-permeable SOD mimetic Mn(III)tetra(4-benzoic acid)porphyrin chloride normalized relaxation to ACh and DEA-NONOate. Furthermore, production of superoxide anion in aorta and serum levels of amyloid P component, which is the murine analog of C-reactive protein, was increased in old mice. In aorta, neither the concentration of BH4nor the ratio of reduced BH4to the oxidation products were different between young and aged mice. Our results demonstrate that in mice, aging impairs relaxation mediated by NO most likely by increased formation of superoxide anion. Oxidation of BH4does not appear to be an important mechanism underlying vasomotor dysfunction in aged mouse arteries.
Nitric oxide and H2O2 contribute to reactive dilation of isolated coronary arterioles
Authors: Koller Akos , Bagi Zsolt
Published: August 2004

The role of metabolic factors derived from cardiac muscle in the development of reactive hyperemia after brief occlusions of the coronary circulation seems to be well established. However, the contribution of occlusion-induced changes in hemodynamic forces to eliciting reactive hyperemia is less known. We hypothesized that in isolated coronary arterioles changes in intraluminal pressure and flow, during and after release of occlusion (O/R), themselves via activating intrinsic mechanosensitive mechanisms, elicit release of vasoactive factors resulting in reactive dilations. Thus in isolated coronary arterioles (diameter: 88 ± 8 μm) changes in diameter to changes in pressure or pressure plus flow (P+F) during and after a brief period (30, 60, and 120 s) of O/R of cannulating tube were measured by videomicroscopy. In response to both types of O/R, diameter first decreased, then, subsequently increased during occlusions. When only pressure was changed (from 80-10-80 mmHg), after release of occlusion, peak dilations increased as a function of the duration of occlusions. After flow was established (30 μl/min), O/R elicited changes in both pressure and flow (from 80-10-80 mmHg and from 0 to 30 μl/min). In these conditions, after the release of occlusions, not only the peak but also the duration of reactive dilation increased significantly as a function of the length of occlusions. The dilations during, and peak dilations after occlusions both in pressure and P+F protocols were significantly reduced by the inhibition of NO synthase with Nω-nitro-l-arginine-methyl-ester (l-NAME) or by endothelium removal, whereas duration of postocclusion dilations were reduced by l-NAME or by endothelium removal only in P+F protocols. Furthermore, in both protocols, catalase significantly reduced the peak but not the duration of reactive dilations. Thus, mechanosensitive mechanisms that are sensitive to deformation, pressure, stretch, and wall shear stress elicit release of NO and H2O2, resulting in reactive dilation of isolated coronary arterioles.
Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock
Authors: Minneci Peter C. , Deans Katherine J. , Banks Steven M. , Costello Renee , Csako Gyorgy , Eichacker Peter Q. , Danner Robert L. , Natanson Charles , Solomon Steven B.
Published: August 2004

During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 μg·kg−1·min−1), norepinephrine (0.2, 1.0, or 2.0 μg·kg−1·min−1), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival ( P < 0.06), mean arterial pressure (MAP) ( P < 0.05), cardiac index (CI) ( P < 0.02), and ejection fraction (EF) ( P = 0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin ( P = 0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose ( P = 0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis.
Nitric oxide synthase-inhibition hypertension is associated with altered endothelial cyclooxygenase function
Authors: Bratz Ian N. , Kanagy Nancy L.
Published: August 2004

We reported previously that endothelium-intact superior mesenteric arteries (SMA) from Nω-nitro-l-arginine (l-NNA)-treated hypertensive rats (LHR) contract more to norepinephrine (NE) than SMA from control rats. Others have shown that nitric oxide (NO) synthase (NOS) inhibition increases cyclooxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS-induced dilation and increased COX product-induced constriction. We observed that the EC50 for NE is lower in LHR SMA compared with control SMA (control −6.37 ± 0.04, LHR −7.89 ± 0.09 log mol/l; P < 0.05). Endothelium removal lowered the EC50 (control −7.95 ± 0.11, LHR −8.44 ± 0.13 log mol/l; P < 0.05) and increased maximum tension in control (control 1,036 ± 38 vs. 893 ± 21 mg; P < 0.05) but not LHR (928 ± 30 vs. 1,066 ± 31 mg) SMA. Thus augmented NE sensitivity in LHR SMA depends largely on decreased endothelial dilation. NOS inhibition (l-NNA, 10−4 mol/l) increased maximum tension and EC50 in control arteries but not in LHR arteries. In contrast, COX inhibition decreased maximum tension in control arteries, suggesting that COX products augment contraction. Indomethacin did not affect NE-induced contraction in l-NNA-treated or denuded arteries. In control SMA loaded with the fluorescent NO indicator 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, indomethacin increased and l-NNA decreased NO release. Therefore, COX products appear to inhibit NO production to augment NE-induced contraction. With chronic NOS inhibition, this modulating influence is greatly diminished. Thus, in NOS-inhibition hypertension, decreased activity of both COX and NOS pathways profoundly disrupts endothelial modulation of contraction.