bluuebunny/crossref_metadata_2025 huggingface dataset:
ASYMMETRICAL QUANTUM KEY DISTRIBUTION PROTOCOL
Authors: LI XIAOYU
Published: April 2003

We provide an asymmetrical quantum key distribution protocol based on the correlations of EPR pairs. It is a variant of the modified Lo–Chau protocol where the EPR pair is not in the state Φ+ but is in one of the four states {Φ±, Ψ±}. The two sides communicating with each other are not equal in the process of establishing the key. A public key system can be built on the protocol. It differs from classical public key system in that there are three keys: the public key, the secret key and the real key.
COEXISTENCE OF OPPOSITE GLOBAL SOCIAL FEELINGS: THE CASE OF PERCOLATION DRIVEN INSECURITY
Authors: PAJOT STÉPHANE , GALAM SERGE
Published: April 2003

A model of the dynamics of appearance of a new collective feeling, in addition and opposite to an existing one, is presented. Using percolation theory, the collective feeling of insecurity is shown to be able to coexist with the opposite collective feeling of safety. Indeed this coexistence of contradictory social feelings result from the simultaneous percolation of two infinite clusters of people who are respectively experiencing a safe and unsafe local environment. Therefore opposing claims on national debates over insecurity are shown to be possibly both valid.
A GUIDED MONTE CARLO METHOD FOR OPTIMIZATION PROBLEMS
Authors: LI S. P.
Published: April 2003

We introduce a new Monte Carlo algorithm which incorporates a guiding function to the conventional Monte Carlo method. In this way, the efficiency of Monte Carlo methods is drastically improved. Two more ingredients, namely, the elimination of irrelevant degrees of freedom and the concept of optimal temperature are also introduced which can further speed up the search process. We use this algorithm to search for the optimal path of the traveling salesman problem and the ground state energy of the Anderson–Edwards spin glass model and demonstrate that its performance is comparable with more elaborate and heuristic methods.
TEACHING SCIENCE USING A MOBILE PHONE
Authors: HEERMANN DIETER W.
Published: April 2003

Mobile phones are very useful devices. One can phone with them and one can also use them to reach and teach students in high schools as well as in universities. To this end, with an example, the feasibility of the approach was demonstrated. A science simulation using the processing power of the phone was also shown.
EVIDENCE FOR SHARPER THAN EXPECTED TRANSITION BETWEEN METASTABLE AND UNSTABLE STATES
Authors: HEERMANN DIETER W. , CORDEIRO CLAUDETTE E.
Published: April 2003

We have analyzed the lifetimes of states by considering the relaxation trajectories following a quench. The average lifetimes, as a function of the quench depth into the two-phase region, shows a very sharp drop defining a limit of stability for metastable states. Using the limit of stability we define a line similar to a spinodal in the two-phase region.
CP VIOLATION IN SUPERSYMMETRIC THEORIES
Authors: KHALIL SHAABAN
Published: April 2003

We review the present status of the CP violating problem in supersymmetric extensions of the standard model. We analyze the constraints imposed by the experimental limits of the electron, neutron, and mercury electric dipole moments on the supersymmetric CP phases and show that only the scenarios with flavour-off-diagonal CP violation remain attractive. These scenarios require Hermitian Yukawa matrices which naturally arise in models with left–right symmetry or a SU(3) flavour symmetry. In this case, εK and ε′/ε can be saturated by a small non-universality of the soft scalar masses through the gluino and chargino contributions respectively. The model also predicts a strong correlation between A CP (b → sγ) and the neutron electric dipole moment. In this framework, the standard model gives a the leading contribution to the CP asymmetry in B → ψKS decay, while the dominant chargino contribution to this asymmetry is < 0.2. Thus, no constraint is set on the non-universality of this model by the recent BaBar and Belle measurements.
DBI ACTION FROM CLOSED STRINGS AND D-BRANE SECOND QUANTIZATION
Authors: KOGAN IAN I. , POLYAKOV DIMITRI
Published: April 2003

Brane-like vertex operators play an important role in a world-sheet formulation of D-branes and M theory. In this paper we derive the DBI D-brane action from closed NSR string with brane-like states. We also show that these operators carry RR charges and define D-brane wave functions in a second quantized formalism.
THE SIGMA MODEL FORMULATION OF TYPE II STRING THEORY IN THE AdS5 × S5 BACKGROUNDS WITH RAMOND–RAMOND FLUX
Authors: NAIK SATCHIDANANDA
Published: April 2003

A sigma model action is constructed for the type II string in the AdS 5 × S5 backgrounds with Ramond–Ramond flux.
A NOTE ON NONCOMMUTATIVE STRING THEORY AND ITS LOW ENERGY LIMIT
Authors: PAL SHESANSU SEKHAR
Published: April 2003

The noncommutative string theory is described by embedding open string theory in a constant second rank antisymmetric Bμν field and the noncommutative gauge theory is defined by a deformed ⋆ product. As a check, the study of various scattering amplitudes in both noncommutative string and noncommutative gauge theory confirms that in the α′ → 0 limit, the noncommutative string theoretic amplitude goes over to the noncommutative gauge theoretic amplitude and the couplings are related as [Formula: see text]. Furthermore, we show that in this limit there will not be any correction to the gauge theoretic action because of the absence of massive modes. We get sin/cos factors in the scattering amplitudes depending on the odd/even number of external photons.
SPIN PHYSICS EXPERIMENTS AT SLAC
Authors:   for the E155/E155x Collaborations, Supported by the National Science Foundation and the Department of Energy contract DE–AC03–76SF00515., BOSTED P.
Published: April 2003

Some recent results on the g1 and g2 spin structure functions of the proton and neutron are presented. New data on the inclusive photoproduction of negative hadrons from transversely polarized protons and deuterons are shown for the first time. Plans for future experiments using polarized photon beams are discussed.
TRANSVERSE Λ POLARIZATION IN INCLUSIVE PROCESSES
Authors: ANSELMINO M. , BOER D. , D'ALESIO U. , MURGIA F.
Published: April 2003

A formalism proposed to study transverse Λ polarization in unpolarized hadronic processes, based on a generalized pQCD factorization theorem, is extended to semi-inclusive DIS. Analytical expressions and examples of numerical estimates are given.
TRANSVERSITY AND LAMBDA PHYSICS AT HERMES
Authors:   for the HERMES Collaboration, SCHNELL G.
Published: April 2003

Spin physics is the main part of the HERMES physics program. In five years of data taking with longitudinally polarized targets HERMES, among many other things, measured for the first time single-spin azimuthal asymmetries in semi-inclusive pion lepto-production. HERMES will now run with a transversely polarized target, the main goal being the first measurement of the u-quark transversity distribution. HERMES will also continue its Λ polarization measurements. Preliminary results from the 1996-2000 data taking period will be presented on the longitudinal spin transfer in semi-inclusive Λ production as well as on the transverse polarization of Λ hyperons produced in quasi-real photo-production.
THE PUZZLE OF THE BOTTOM QUARK PRODUCTION CROSS SECTION
Authors: BERGER EDMOND L.
Published: April 2003

The production rate of bottom quarks at hadron colliders exceeds the expectations of next-to-leading order perturbative quantum chromodynamics. An additional contribution from pair-production of light gluinos, of mass 12 to 16 GeV, with two-body decays into bottom quarks and light bottom squarks, yields a differential cross section for bottom quarks in better agreement with data. The masses of the gluino and bottom squark are restricted further by the ratio of like-sign to opposite-sign leptons at hadron colliders. Restrictions on this scenario from other data are summarized, and predictions are made for other processes such as Upsilon decay into a pair of bottom squarks.
FLAVOR-SPIN SYMMETRY AND THE TENSOR CHARGE
Authors: GAMBERG LEONARD , GOLDSTEIN GARY R.
Published: April 2003

Exploiting an approximate phenomenological symmetry of the JPC = 1+- light axial vector mesons and using pole dominance, we calculate the flavor contributions to the nucleon tensor charge. The result depends on the decay constants of the axial vector mesons and their couplings to the nucleons.
SPIN AND OTHER ASPECTS OF GENERALIZED PARTON DISTRIBUTIONS
Authors: DIEHL MARKUS
Published: April 2003

I discuss how generalized parton distribution probe various aspects of QCD bound states. Topics include the interplay between transverse and longitudinal structure, quantum mechanical interference, orbital angular momentum, helicity flip, and higher-spin targets.
FINAL-STATE INTERACTIONS AND SINGLE-SPIN ASYMMETRIES IN SEMI-INCLUSIVE DEEP INELASTIC SCATTERING
Authors: BRODSKY STANLEY J. , HWANG DAE SUNG , SCHMIDT IVAN
Published: April 2003

Recent measurements from the HERMES and SMC collaborations show a remarkably large azimuthal single-spin asymmetries AUL and AUT of the proton in semi-inclusive pion leptoproduction γ*(q) p → π X. We show that final-state interactions from gluon exchange between the outgoing quark and the target spectator system leads to single-spin asymmetries in deep inelastic lepton-proton scattering at leading twist in perturbative QCD; i.e., the rescattering corrections are not power-law suppressed at large photon virtuality q2 at fixed xbj. The existence of such single-spin asymmetries requires a phase difference between two amplitudes coupling the proton target with [Formula: see text] to the same final-state, the same amplitudes which are necessary to produce a nonzero proton anomalous magnetic moment. We show that the exchange of gauge particles between the outgoing quark and the proton spectators produces a Coulomb-like complex phase which depends on the angular momentum Lz of the proton's constituents and thus is distinct for different proton spin amplitudes. The single-spin asymmetry which arises from such final-state interactions does not factorize into a product of structure function and fragmentation function, and it is not related to the transversity distribution δq(x,Q) which correlates transversely polarized quarks with the spin of the transversely polarized target nucleon.
SPIN PHYSICS WITH STAR
Authors:   for the STAR Collaboration, KIRYLUK JOANNA
Published: April 2003

The STAR collaboration aims to study polarized proton-proton collisions at RHIC. The emphasis of the spin run this year is on transverse single spin asymmetries. Beyond 2001, we aim to determine directly and precisely the gluon polarization, as well as the polarizations of the u, [Formula: see text], d and [Formula: see text] quarks in the proton by measuring in addition longitudinal and double spin asymmetries. Furthermore, we aim to measure for the first time the quark transversity distributions. These measurements will improve substantially the knowledge and understanding of the spin structure of the nucleon.
CONNECTING STRUCTURE FUNCTIONS ON THE LATTICE WITH PHENOMENOLOGY
Authors: DETMOLD W. , MELNITCHOUK W. , THOMAS A. W.
Published: April 2003

We examine the extraction of moments of parton distributions from lattice data, focusing in particular on the chiral extrapolation as a function of the quark mass. Inclusion of the correct chiral behavior of the spin-averaged isovector distribution resolves a long-standing discrepancy between the lattice moments and experiment. We extract the x-dependence of the valence u - d distribution from the lowest few lattice moments, and discuss the implications for the quark mass dependence of meson masses lying on the a2 Regge trajectory. The role of chiral symmetry in spin-dependent distributions, and in particular the lattice axial vector charge, gA, is also highlighted.
SPIN ALIGNMENT OF HEAVY MESON REVISITED
Authors: MA J. P.
Published: April 2003

Using heavy quark effective theory a factorized form for inclusive production rate of a heavy meson can be obtained, in which the nonperturbative effect related to the heavy meson can be characterized by matrix elements defined in the heavy quark effective theory. Using this factorization, predictions for the full spin density matrix of a spin-1 and spin-2 meson can be obtained and they are characterized only by one coefficient representing the nonperturbative effect. Predictions for spin-1 heavy meson are compared with experiment performed at e+e- colliders in the energy range from [Formula: see text] to [Formula: see text], a complete agreement is found for D*- and B*-meson. There are distinct differences from the existing approach and they are discussed.
ORIGINS OF SINGLE TRANSVERSE SPIN ASYMMETRIES
Authors: ANSELMINO M. , BOGLIONE M. , D'ALESIO U. , MURGIA F.
Published: April 2003

Single transverse spin asymmetries in pp → πX and ℓp → ℓπX processes have been observed; their possible origins and connections are investigated. A phenomenological description within a pQCD generalized factorization scheme is discussed.
DOUBLE SPIN ASYMMETRY IN SEMI-INCLUSIVE DEEP INELASTIC SCATTERING
Authors: DI SALVO ELVIO
Published: April 2003

We shortly review the various methods suggested for determining the transversity function. Among such methods, we consider especially those based on semi-inclusive deep inelastic scattering. In the framework of this kind of reactions, we propose to measure a double spin asymmetry, using a transversely polarized proton target and a longitudinally polarized lepton beam, and fixing the direction of the final pion. Under particular conditions, the asymmetry is sensitive to the transversity function.
TRANSVERSITY AND AZIMUTHAL SPIN ASYMMETRY OF PION ELECTROPRODUCTION
Authors: MA BO-QIANG
Published: April 2003

The quark transversity distributions are discussed in a light-cone SU(6) quark-diquark model and in a perturbative QCD based analysis. The azimuthal spin asymmetries, both for charged and neutral pion production in semi-inclusive deep inelastic scattering of unpolarized charged lepton beams on longitudinally and transversely polarized nucleon targets, are analyzed. It is found that different approaches to the distribution and fragmentation functions may lead to quite different predictions. It is also found that the unfavored quark to pion fragmentation functions should be taken into account for π- production from a proton target.
CALCULATING SPIN-DEPENDENT PARTON DISTRIBUTIONS IN THE BAG MODEL
Authors: SIGNAL A. I.
Published: April 2003

Model calculations of parton distributions are an important way to connect our knowledge of physics at high energy scales with physics at lower energy scales typical of nuclear physics. Earlier work on the spin-independent valence quark distributions has shown that DIS data support a bag radius around 0.8 fm, and highlighted the importance of chiral symmetry and the role of the pion cloud in nucleon structure. Here, that work is extended to the spin-dependent parton distributions. We calculate these distributions in the model and compare with experimental data.
SPIN STRUCTURE FUNCTIONS AND INTRINSIC MOTION OF THE CONSTITUENTS
Authors: ZÁVADA PETR
Published: April 2003

The spin structure functions of the system of quasifree fermions on mass shell are studied in a consistently covariant approach. Comparison with the basic formulas following from the quark-parton model reveals the importance of the fermion motion inside the target for the correct evaluation of the spin structure functions. In particular it is shown, that regarding the moment Γ1, both the approaches are equivalent for the static fermions, but differ by the factor 1/3 in the limit of massles fermions (m ≪ p0, in target rest frame). Some other sum rules are discussed as well.
TWIST-3 EFFECTS IN POLARIZED PHOTON STRUCTURE
Authors: BABA HIDESHI , SASAKI KEN , UEMATSU TSUNEO
Published: April 2003

The polarized photon structure is described by two spin structure functions [Formula: see text] and [Formula: see text] which can be studied in the future polarized ep or e+e- colliders. Here we investigate the QCD twist-3 effects in [Formula: see text] to the leading order in QCD.
B → K* ℓ+ ℓ- DECAYS WITH POLARIZED K*
Authors: CHEN C. H. , GENG C. Q.
Published: April 2003

We study the exclusive decays of B → K* ℓ+ ℓ- within the framework of the PQCD. We obtain the form factors for the B → K* transition in the large recoil region, where the PQCD for heavy B meson decays is reliable. We find that the form factors at q2 = 0 are consistent with those from the large energy effective theory combined with the heavy quark effective theory and the experiment of B → K*γ. Via the decay chain of B → K* (Kπ) ℓ+ ℓ-, we can study many physical observables which are related to the different helicity combinations of B → K* ℓ+ ℓ-, such as the forward-backward asymmetries (FBAs). In particular, we can study the T violating effect which is small in the standard model but can be up to 10% in models with new physics.
POLARIZED s-QUARK DISTRIBUTION IN CHARMED HADRON LEPTOPRODUCTION
Authors: SUDOH KAZUTAKA
Published: April 2003

In order to extract the polarized strange quark density in proton, we studied the semi–inclusive [Formula: see text] leptoproduction in charged current DIS at THERA energies. We indicate that measurements of the spin correlation between the incident proton and the produced [Formula: see text] baryon gives us information about the polarized strange quark distribution.
CHARMED HADRON PRODUCTION AT RHIC
Authors: OHKUMA KAZUMASA , MORII TOSHIYUKI , OYAMA SATOSHI
Published: April 2003

To extract information about polarized gluon distribution in the proton, charmed hadron, actually [Formula: see text], productions at RHIC experiment are studied. We found that the spin correlation asymmetry between the initial proton and the produced [Formula: see text] is enable us to distinguish parameterization models of polarized gluons.
SPIN ALIGNMENT OF VECTOR MESON IN HIGH ENERGY REACTIONS
Authors: XU QING-HUA , LIU CHUN-XIU , LIANG ZUO-TANG
Published: April 2003

The recent data on the polarization of vector meson at LEP show that the vector mesons favor the helicity zero state. We calculate the helicity density matrix of vector meson which contains a polarized fragmenting quark by adding the spin of the fragmenting quark and that of the antiquark created in the fragmentation. The data at LEP imply a significant polarization for the antiquark in the opposite direction as that of the fragmenting quark. We extend the calculations to other reactions and make predictions for vector mesons in deeply inelastic lepton-nucleon scatterings and polarized pp collisions.
STATUS OF SPIN PHYSICS: EXPERIMENTAL SUMMARY
Authors: PENG JEN-CHIEH
Published: April 2003

The current status of spin physics experiments, based on talks presented at the Third Circum-Pan-Pacific Symposium on High Energy Spin Physics held in Beijing, 2001, is summarized in this article. Highlights of recent experimental results at SLAC, JLab, and DESY, as well as future plans at these facilities and at RHIC-spin are discussed.
HADRON SPIN DYNAMICS
Authors: BRODSKY STANLEY J.
Published: April 2003

Spin effects in exclusive and inclusive reactions provide an essential new dimension for testing QCD and unraveling hadron structure. Remarkable new experiments from SLAC, HERMES (DESY), and Jefferson Lab present many challenges to theory, including measurements at HERMES and SMC of the single spin asymmetries in ep → e′ π X where the proton is polarized normal to the scattering plane. This type of single spin asymmetry may be due to the effects of rescattering of the outgoing quark on the spectators of the target proton, an effect usually neglected in conventional QCD analyses. Many aspects of spin, such as single-spin asymmetries and baryon magnetic moments are sensitive to the dynamics of hadrons at the amplitude level, rather than probability distributions. I will illustrate the novel features of spin dynamics for relativistic systems by examining the explicit form of the light-front wavefunctions for the two-particle Fock state of the electron in QED, thus connecting the Schwinger anomalous magnetic moment to the spin and orbital momentum carried by its Fock state constituents and providing a transparent basis for understanding the structure of relativistic composite systems and their matrix elements in hadronic physics. I also present a survey of outstanding spin puzzles in QCD, particularly ANN in elastic pp scattering, the J/ψ → ρπ puzzle, and J/ψ polarization at the Tevatron.
LEAKAGE CURRENT IN DEEP-SUBMICRON CMOS CIRCUITS
Authors: ROY KAUSHIK , MUKHOPADHYAY SAIBAL , MAHMOODI-MEIMAND HAMID
Published: April 2003

The high leakage current in deep submicron regimes is becoming a significant contributor to the power dissipation of CMOS circuits as the threshold voltage, channel length, and gate oxide thickness are reduced. Consequently, the identification and modeling of different leakage components is very important for the estimation and reduction of leakage power, especially in the low power applications. This paper explores the various transistor intrinsic leakage mechanisms including the weak inversion, the drain-induced barrier lowering, the gate-induced drain leakage, and the gate oxide tunneling.
POWER ESTIMATION AND POWER OPTIMAL COMMUNICATION IN DEEP SUBMICRON BUSES: ANALYTICAL MODELS AND STATISTICAL MEASURES
Authors: SOTIRIADIS PAUL P. , CHANDRAKASAN ANANTHA
Published: April 2003

Reduction of power dissipation in digital circuits is a subject of research in industry and academia. A major component of power dissipation in modern microprocessors is due to their large interconnect networks which are responsible for the distribution of power and clocks as well as for the intra-chip communication. Communication is realized by data and address buses. In this paper we (i) discuss an analytical model for energy estimation in deep submicron buses, (ii) present statistical energy measures based on the analytical model, (iii) derive the energy limits of communication through buses, (iv) and introduce energy efficiency measures of communication.
LEAKAGE CURRENT REDUCTION IN VLSI SYSTEMS
Authors: BLAAUW DAVID , MARTIN STEVE , MUDGE TREVOR , FLAUTNER KRISZTIAN
Published: April 2003

There is a growing need to analyze and optimize the stand-by component of power in digital circuits designed for portable and battery-powered applications. Since these circuits remain in stand-by (or sleep) mode significantly longer than in active mode, their stand-by current, and not their active switching current, determines their battery life. Hence, stringent specifications are being placed on the stand-by (or leakage) current drawn by such devices. As the power supply voltage is reduced, the threshold voltage of transistors is scaled down to maintain a constant switching speed. Since reducing the threshold voltage increases the leakage of a device exponentially, leakage current has become a dominant factor in the design of VLSI circuits. In this paper, we describe a method that uses simultaneous dynamic voltage scaling (DVS) and adaptive body biasing (ABB) to reduce the total power consumption of a processor under dynamic computational workloads. Analytical models of the leakage current, dynamic power, and frequency as a function of supply voltage and body bias are derived and verified with SPICE simulation. Given these models, we show how to derive an analytical expression for the optimal trade-off between supply voltage and body bias, given a required clock frequency and duration of operation. The proposed method is then applied to a processor and is compared with DVS alone for workloads obtained using real-time monitoring of processor utilization for four typical applications.
INTEGRATED PERFORMANCE, POWER, AND THERMAL MODELING
Authors: CAI GEORGE , DHODAPKAR ASHUTOSH S. , SMITH JAMES E.
Published: April 2003

In current microprocessor designs, power dissipation has become a first class design constraint alongside performance and total chip cost. In order to design power efficient microprocessors, it is essential for architects to estimate the power/energy consumption and study thermal effects early on in the design process. This paper describes a method that can be used to study power/performance tradeoffs during the microarchitecture definition phase. The modeling and simulation methods provide an integrated framework for evaluating the effects of microarchitectural parameters on performance, power and thermal behavior. The method also provides a flexible interface for supporting several power and thermal models of varying degrees of detail. The paper introduces a tool based on this method that can be used to systematically study new architectures, designs and optimize them for power and/or performance. The tool also has a flexible interface which is to be easily extended for future power/performance analysis and optimization techniques.
Association Between Complement Factor H and Proteoglycans in Early Human Coronary Atherosclerotic Lesions
Authors: Oksjoki Riina , Jarva Hanna , Kovanen Petri T. , Laine Petri , Meri Seppo , Pentikäinen Markku O.
Published: April 2003

Objective—Complement activation has been suggested to play a role in atherogenesis. To study the regulation of complement activation in human coronary atherosclerotic lesions, we examined the spatial relationships between the major complement inhibitor, factor H, and the complement activation products C3d and C5b-9.

Methods and Results—In early lesions (American Heart Association types II and III), factor H was immunohistochemically found in the superficial proteoglycan-rich layer in association with numerous macrophages and C3d, whereas C5b-9 was found deeper in the intima, where factor H was virtually absent. In vitro experiments involving surface plasmon resonance and affinity chromatography analyses demonstrated that isolated human arterial proteoglycans bind factor H, and functional complement assays showed that glycosaminoglycans inhibit the complement activation induced by modified low density lipoprotein or by a foreign surface.

Conclusions—The present observations raise the possibility that proteoglycans, because of their ability to bind the major complement inhibitor factor H, may inhibit complement activation in the superficial layer of the arterial intima. In contrast, deeper in the intima, where factor H and proteoglycans are absent, complement may be activated and proceed to C5b-9. Thus, the superficial and the deep layers of the human coronary artery appear to differ in their ability to regulate complement activation.
Noninvasive Assessment of Arterial Stiffness and Risk of Atherosclerotic Events
Authors: Oliver James J. , Webb David J.
Published: April 2003

Investigation of arterial stiffness, especially of the large arteries, has gathered pace in recent years with the development of readily available noninvasive assessment techniques. These include the measurement of pulse wave velocity, the use of ultrasound to relate the change in diameter or area of an artery to distending pressure, and analysis of arterial waveforms obtained by applanation tonometry. Here, we describe each of these techniques and their limitations and discuss how the measured parameters relate to established cardiovascular risk factors and clinical outcome. We also consider which techniques might be most appropriate for wider clinical application. Finally, the effects of current and future cardiovascular drugs on arterial stiffness are also discussed, as is the relationship between arterial elasticity and endothelial function.
Oncostatin M, an Interleukin-6 Family Cytokine, Upregulates Matrix Metalloproteinase-9 Through the Mitogen-Activated Protein Kinase Kinase-Extracellular Signal-Regulated Kinase Pathway in Cultured Smooth Muscle Cells
Authors: Nagata Tsuyoshi , Kai Hisashi , Shibata Rei , Koga Mitsuhisa , Yoshimura Akihiko , Imaizumi Tsutomu
Published: April 2003

Objectives—Matrix metalloproteinase (MMP)-9 is implicated in extracellular matrix (ECM) degradation of atherosclerotic lesions. Oncostatin M (OSM) regulates ECM metabolism in various kinds of cells. Thus, we sought to investigate whether OSM regulates MMP-9 expression in cultured rat aortic smooth muscle cells (SMCs) and, if so, to determine the signaling pathway for MMP-9 induction by OSM.

Methods and Results—Competitive reverse transcriptase polymerase chain reaction showed that OSM upregulated MMP-9 mRNA expression, peaking at 4 hours and returning to unstimulated levels by 24 hours. Gelatin zymography revealed that MMP-9 activity was increased in the conditioned medium after the 24-hour OSM treatment. Immunoblot analysis demonstrated that OSM transiently induced extracellular signal-regulated kinase (ERK)1/2 and STAT3 phosphorylations with a peak at 15 and 5 minutes, respectively. A MEK1 inhibitor, PD98059, not only blocked ERK1/2 phosphorylation but also abolished the OSM-induced MMP-9 upregulation, whereas the MMP-9 induction was not affected by overexpressing dominant-negative STAT3. In addition, OSM slightly upregulated MMP-2 and downregulated tissue inhibitors of MMP-1 and -3 through different mechanisms from that in case of MMP-9.

Conclusions—OSM upregulates MMP-9 expression in SMCs through the MEK-ERK but not STAT3 pathway.
TWEAK Is an Endothelial Cell Growth and Chemotactic Factor That Also Potentiates FGF-2 and VEGF-A Mitogenic Activity
Authors: Donohue Patrick J. , Richards Christine M. , Brown Sharron A.N. , Hanscom Heather N. , Buschman John , Thangada Shobha , Hla Timothy , Williams Mark S. , Winkles Jeffrey A.
Published: April 2003

Objective—

TWEAK, a member of the tumor necrosis factor superfamily, binds to the Fn14 receptor and stimulates angiogenesis in vivo. In this study, we investigated Fn14 gene expression in human endothelial cells (ECs) and examined the effect of TWEAK, added either alone or in combination with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor-A (VEGF-A), on EC proliferation, migration, and survival in vitro. We also determined whether a soluble Fn14-Fc fusion protein could inhibit TWEAK biologic activity on ECs and investigated TWEAK signal transduction in ECs.

Methods and Results—

We found that both FGF-2 and VEGF-A could induce Fn14 mRNA expression in ECs. TWEAK was a mitogen for ECs, and this proliferative activity could be inhibited by an Fn14-Fc decoy receptor. Furthermore, TWEAK treatment activated several intracellular signaling pathways in ECs and potentiated FGF-2– and VEGF-A–stimulated EC proliferation. TWEAK also had EC chemotactic activity, but it did not promote EC survival.

Conclusions—

These results indicate that TWEAK is an EC growth and migration factor but not a survival factor. TWEAK can also enhance both FGF-2 and VEGF-A mitogenic activity on ECs. Thus, TWEAK may act alone as well as in combination with FGF-2 or VEGF-A to regulate pathological angiogenesis.
Enzymatically Modified LDL Induces Cathepsin H in Human Monocytes
Authors: Han Shan-Rui , Momeni Arash , Strach Katharina , Suriyaphol Prapat , Fenske Dominic , Paprotka Kerstin , Hashimoto Shin Ichi , Torzewski Michael , Bhakdi Sucharit , Husmann Matthias
Published: April 2003

Objective—Modification with proteases and cholesterylesterase transforms LDL to a moiety that resembles lipoproteins isolated from atherosclerotic lesions and possesses atherogenic properties. To identify changes in monocyte-derived foam cells laden with enzymatically modified LDL (E-LDL), we compared patterns of the most abundant transcripts in these cells after incubation with LDL or E-LDL.

Methods and Results—Serial analyses of gene expression (SAGE) libraries were constructed from human monocytes after treatment with LDL or E-LDL. Several tags were differentially expressed in LDL-treated versus E-LDL–treated cells, whereby marked selective induction by E-LDL of cathepsin H was conspicuous. We show that cathepsin H is expressed in atherosclerotic lesions in colocalization with E-LDL. Furthermore, we demonstrate that LDL modified with cathepsin H and cholesterylesterase can confer onto LDL the capacity to induce macrophage foam cell formation and to induce cathepsin H.

Conclusions—Cathepsin H could contribute to the transformation of LDL to an atherogenic moiety; the process might involve a self-sustaining amplifying circle.
Elastogenesis in Human Arterial Disease
Authors: Krettek Alexandra , Sukhova Galina K. , Libby Peter
Published: April 2003

Objective—

Elastin, an extracellular matrix protein, constitutes about 30% of the dry weight of the arteries. Elastolysis induced by inflammatory processes is active in chronic arterial diseases. However, elastogenesis in arterial diseases has received little attention. In this work we hypothesized that disordered elastogenesis is active in matrix remodeling in atheroma and abdominal aortic aneurysm (AAA).

Methods and Results—

Human AAA and atheroma have 4- to 6-fold more tropoelastin protein than nondiseased arteries. The smooth muscle cell–containing media and fibrous cap of atherosclerotic arteries contain ordered mature elastin, whereas macrophage (MΦ)-rich regions often have disorganized elastic fibers. Surprisingly, in addition to smooth muscle cells, MΦs in diseased arteries also produce the elastin precursor tropoelastin, as shown by double immunostaining, in situ hybridization, and reverse transcription–polymerase chain reaction for tropoelastin mRNA. Cultured monocyte-derived MΦs can express the elastin gene. AAA have 9-fold but atheroma only 1.6-fold lower levels of desmosine, a marker for mature cross-linked elastin, than normal arteries.

Conclusions—

This study demonstrates ongoing but often ineffective elastogenesis in arterial disease and establishes human macrophages as a novel source for this important matrix protein. These results have considerable import for understanding mechanisms of extracellular matrix remodeling in arterial diseases.
Lack of Interleukin-1β Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice
Authors: Kirii Hirokazu , Niwa Tamikazu , Yamada Yasuhiro , Wada Hisayasu , Saito Kuniaki , Iwakura Yoichiro , Asano Masahide , Moriwaki Hisataka , Seishima Mitsuru
Published: April 2003

Objective—

Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1β (IL-1β), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis.

Methods and Results—

We generated mice lacking both apoE and IL-1β. The sizes of atherosclerotic lesions at the aortic sinus in apoE−/−/IL-1β−/−mice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoE−/−/IL-1β
+/+
mice, and the percentage of the atherosclerotic area to total area of apoE−/−/IL-1β−/− at 24 weeks of age also showed a significant decrease of about 30% compared with apoE−/−/IL-1β
+/+
. The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoE−/−/IL-1β−/− aorta were significantly reduced compared with the apoE−/−/IL-1β
+/+
. Furthermore, VCAM-1 was also reduced at the protein level in apoE−/−/IL-1β−/− aorta compared with apoE−/−/IL-1β
+/+
.

Conclusions—

The lack of IL-1β decreases the severity of atherosclerosis in apoE deficient mice, possibly through increased expressions of VCAM-1 and monocyte chemotactic protein-1 in the aorta.
Low Density Lipoproteins Interact With Acidic Fibroblast Growth Factor and Modify Its Function
Authors: Ananyeva Natalya , Tjurmin Alexey , Saenko Evgueni , Haudenschild Christian
Published: April 2003

Objective—

Oxidized LDL (oxLDL) was shown to trigger the release of acidic fibroblast growth factor (FGF-1). Because these components are likely to be present simultaneously in the atherosclerotic milieu, we investigated whether oxLDL interacts with FGF-1 and whether this interaction affects FGF-1 functioning.

Methods and Results—

Using molecular sieve and electrophoretic mobility shift assays, we found that FGF-1 forms a complex with oxLDL in vitro, in contrast to its low affinity for nonatherogenic, native LDL. The FGF-1/oxLDL complex had a dramatically decreased ability to bind heparin and was nonmitogenic on cultured smooth muscle cells. In human atherosclerotic lesions, the highest FGF-1 immunoreactivity was found in macrophages. With respect to oxLDL accumulation, 2 patterns were distinguished: (1) moderate, intracellular in matrix-rich regions containing viable cells and (2) massive, both cell-associated and extracellular oxLDL deposits in foam cell–rich regions with necrotic areas. The proliferating cell nuclear antigen readings for proliferating cells reflected that the mitogenic activity of FGF-1 was confined to the regions where oxLDL was strictly intracellular and was inhibited in the regions with extracellular oxLDL deposition.

Conclusions—

oxLDL, besides being a bulky component of the atherosclerotic lesion, possibly manifests its pathogenicity by complexing FGF-1 and inhibiting its growth-promoting function during atherogenesis.
Nebivolol Prevents Vascular NOS III Uncoupling in Experimental Hyperlipidemia and Inhibits NADPH Oxidase Activity in Inflammatory Cells
Authors: Mollnau Hanke , Schulz Eberhard , Daiber Andreas , Baldus Stephan , Oelze Matthias , August Michael , Wendt Maria , Walter Ulrich , Geiger Carolin , Agrawal Rahul , Kleschyov Andrei L. , Meinertz Thomas , Münzel Thomas
Published: April 2003

Objectives—

Nebivolol, in contrast to other selective β
1
-adrenergic receptor antagonists like atenolol, improves endothelial function in patients with oxidative stress within vascular tissue. With the present studies we sought to determine whether β receptor blockade with nebivolol may improve endothelial function in hyperlipidemia and whether this is attributable to reductions in vascular oxidative stress.

Methods and Results—

Watanabe heritable hyperlipidemic rabbits (WHHL) were treated with nebivolol (10 mg/kg per day for 8 weeks). New Zealand white rabbits (NZWR) served as controls. Nebivolol improved endothelial function, reduced vascular superoxide and vascular macrophage infiltration, and prevented NO synthase uncoupling in WHHL. Nebivolol treatment did not modify the expression of sGC or cGK-I but improved cGK-I activity (assessed by the phosphorylation state of the VAsodilator Stimulated Phosphoprotein at serine
239
, P-VASP). NAD(P)H oxidase activity in whole blood and isolated neutrophils was dose-dependently inhibited by nebivolol, whereas atenolol, metoprolol, and carvedilol were markedly less effective.

Conclusions—

Nebivolol therapy effectively prevents NO synthase III uncoupling and prevents activation of the neutrophil NAD(P)H oxidase and infiltration of inflammatory cells. These novel antioxidative stress actions of this compound may explain partly the beneficial effects on endothelial function in patients with enhanced vascular oxidative stress.
Cardiac Allograft Vasculopathy and Dysregulation of the NO Synthase Pathway
Authors: Weis Michael , Cooke John P.
Published: April 2003

Cardiac allograft vasculopathy is the most aggressive form of atherosclerosis in humans and is the leading cause of death after the first year of heart transplantation. Endothelial dysfunction is a major contributing factor to the acceleration of coronary vascular disease in these individuals. A reflection of this endothelial dysfunction is the severe impairment in endothelium-dependent vasodilation that occurs early after transplantation. The etiology of this allograft endothelial alteration is multifactorial and may include preexisting atherosclerosis of the graft vessels, reperfusion injury during transplantation, denervation, disruption of the lymphatic system, and acute and chronic immune injury, as well as traditional risk factors for coronary artery disease (hyperlipidemia, diabetes, hypertension, or hyperhomocysteinemia) and pathogens, such as cytomegalovirus. The alteration in endothelial function affects vasomotor tone of the coronary arteries. Evidence indicates that there may be an impairment of endothelial production and/or activity of NO. Because NO is a potent vasodilator, its deficiency would explain the abnormal vasomotor tone in these individuals. In addition, because NO inhibits key processes in vascular inflammation and atherosclerosis, its absence may contribute to the acceleration of transplant vascular disease. Recent studies from our group and others have shed light on the mechanisms of endothelial dysfunction and its importance in cardiac allograft vasculopathy. In addition, the alteration in endothelial function contributes to vascular inflammation and progression of the disease.
Circadian Variation of Cardiac K
+
Channel Gene Expression
Authors: Yamashita Takeshi , Sekiguchi Akiko , Iwasaki Yu-ki , Sagara Kouichi , Iinuma Hiroyuki , Hatano Seiji , Fu Long-Tai , Watanabe Hiroshi
Published: April 2003

Background—

Many cardiac arrhythmias have their own characteristic circadian variations. Because the expression of many genes, including clock genes, is regulated variably during a day, circadian variations of ion channel gene expression, if any, could contribute to the fluctuating alterations of cardiac electrophysiological characteristics and subsequent arrhythmogenesis.

Methods and Results—

To examine whether cardiac K
+
channel gene expression shows a circadian rhythm, we analyzed the mRNA levels of 8 Kv and 6 Kir channels in rat hearts every 3 hours throughout 1 day. Among these channels, Kv1.5 and Kv4.2 genes showed significant circadian variations in their transcripts: ≈2-fold increase of Kv1.5 mRNA from trough at Zeitgeber time (ZT) 6 to peak at ZT18 and a completely reverse pattern in Kv4.2 mRNA (≈2-fold increase from trough at ZT18 to peak at ZT6). Actually, along with the variations in the immunoreactive proteins, the density of the transient outward and steady-state currents in isolated myocytes and the responses of atrial and ventricular refractoriness to 4-aminopyridine in isolated-perfused hearts showed differences between ZT6 and ZT18, a circadian pattern comparable to that of Kv1.5 and Kv4.2 gene expression. Reversal of light stimulation almost inverted these circadian rhythms, although pharmacological autonomic blockade only partially attenuated the rhythm of Kv1.5 but not of Kv4.2 transcripts.

Conclusions—

Among all the cardiac K
+
channels, Kv1.5 and 4.2 channels are unique in showing characteristic circadian patterns in their gene expression, with Kv1.5 increase during the dark period partially dependent on β-adrenergic activities and Kv4.2 increase during the light period independent of the autonomic nervous function.
Asymmetric Dimethylarginine, Blood Pressure, and Renal Perfusion in Elderly Subjects
Authors: Kielstein Jan T. , Bode-Böger Stefanie M. , Frölich Jürgen C. , Ritz Eberhard , Haller Hermann , Fliser Danilo
Published: April 2003

Background—

Reduced availability of nitric oxide (NO) is thought to contribute to the age-associated increase of renovascular tone and blood pressure. We assessed blood concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal hemodynamics, comparing young (n=24, 13 men, 25±1 years) and elderly (n=24, 13 men, 69±2 years) healthy subjects and elderly subjects with essential hypertension (n=24, 13 men, 70±2 years).

Methods and Results—

Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (
P
<0.05) and effective renal plasma flow (ERPF) significantly lower (
P
<0.05) in elderly (2.77±0.20 μmol/L, 125±10 mm Hg/mL per minute, 487±26 mL/min per 1.73 m
2
) than in young healthy subjects (1.30±0.11, 77±3, 654±18). Both ADMA levels and RVR were higher and ERPF lower in the hypertensive elderly subjects (3.53±0.23, 163±11, 427±19;
P
<0.05 versus both groups). In contrast, plasma concentrations of the biologically inactive stereoisomer symmetric dimethylarginine,
l
-arginine, and homocysteine were similar in the 3 groups studied. In the logistic regression analysis only ADMA was an independent determinant of both ERPF (
P
<0.001;
r
2
=0.80) and RVR (
P
<0.002;
r
2
=0.86). In addition, ADMA (
P
<0.002) and serum glucose (
P
<0.036) were independently related (
r
2
=0.67) to the level of blood pressure.

Conclusions—

These results are compatible with the notion that accumulation of the endogenous NO synthase inhibitor ADMA in senescent individuals is involved in the decrease of renal perfusion and increase of blood pressure.
Transcutaneous Oxygen Pressure Measurements on the Buttocks During Exercise to Detect Proximal Arterial Ischemia
Authors: Abraham Pierre , Picquet Jean , Vielle Bruno , Sigaudo-Roussel Dominique , Paisant-Thouveny Francine , Enon Bernard , Saumet Jean-Louis
Published: April 2003

Background—

We sought to identify whether transcutaneous oxygen tension (tcP
o
2
) measurements could be used to noninvasively detect lesions in the arterial network supplying blood flow to the hypogastric circulation.

Methods and Results—

A study was undertaken in vascular patients with suspected (PC, n=43) and not with suspected (NPC, n=34) proximal ischemia. TcP
o
2
was measured on both buttocks and with a chest reference electrode. Arteriography on the right or left side was positive for stenoses (≥75%) or occlusion of one or more of the following arteries: the aorta, the common iliac arteries, or the internal iliac arteries. The arteriography was compared with the resting tcP
o
2
values (REST) and with the minimal value (MIN) and maximal change from rest normalized to eventual chest changes (DROP) recorded during or after a treadmill test. REST, MIN, and DROP were, respectively, as follows in positive versus negative arteriograms (mean±SD; in mm Hg): 80.2±10.9 versus 78.6±11.5 (
P
>0.05), 55.2±20.0 versus 69.9±15.8 (
P
<0.001), and −31.8±17.6 versus −9.5±6.4 (
P
<0.0001) in PC and 78.9±14.0 versus 80.5±14.3 (
P
>0.05), 64.4±21.0 versus 75.1±14.6 (
P
<0.02), and −24.1±13.5 versus −8.7±4.8 (
P
<0.0001) in NPC. In PC and NPC respectively, with a cutoff point of −16 and −15 mm Hg, DROP showed, respectively, 83%/82% and 79%/86% sensitivity/specificity in the diagnosis of positive arteriograms.

Conclusions—

Proximal ischemia is a frequent finding in vascular patients. TcP
o
2
measurement on the buttocks during exercise is a sensitive and specific indicator for lesions in the arterial tree toward the hypogastric circulation. Potentially it could objectively assess the response to endovascular or surgical approaches to iliac lesions.
What Induces the Warm-Up Ischemia/Angina Phenomenon: Exercise or Myocardial Ischemia?
Authors: Bogaty Peter , Poirier Paul , Boyer Luce , Jobin Jean , Dagenais Gilles R.
Published: April 2003

Background—

The relation of the warm-up ischemia phenomenon to the presence and intensity of initial myocardial ischemia is unclear. We sought to determine whether the warm-up ischemia phenomenon requires initial myocardial ischemia or can be induced by exercise without ischemia and whether there is a relation between the intensity of initial ischemia and the attenuation of ischemia on reexercise.

Methods and Results—

Twelve subjects with exertional myocardial ischemia performed 2 exercise ECG tests (1 and 2) at a ±10-minute interval on 3 occasions (A, B, C) 1 month apart. A1 and A2 were symptom-limited. B1 was kept as long as A1, but its intensity was held under the ischemic threshold (heart rate×systolic pressure at 1-mm ST depression [STD]) noted at A1. B2 was symptom-limited. C1 was also kept as long as A1 but with an intensity adjusted to maintain one-half maximum STD of A1. C2 was symptom-limited. Exercise duration of A2, B2, and C2 increased similarly compared with A1 (
P
=0.009). However, the ischemic threshold (×10
−3
) increased at A2 (23.5±6.0) compared with A1 (20.3±4.8;
P
<0.0001) but not at B2 (19.8±5.0) or C2 (21.5±5.8). Similarly, maximum STD adjusted to the highest heart rate–systolic pressure product common to A1, A2, B2, and C2 decreased at A2 (1.4±0.7 mm) compared with A1 (2.5±0.9 mm;
P
<0.0001) but not at B2 (2.7±0.9 mm) or C2 (2.3±0.9 mm).

Conclusions—

Exercises under the ischemic threshold and of intermediate ischemic intensity increase short-term exercise capacity, but myocardial ischemia of more than moderate intensity is needed to induce the warm-up ischemia phenomenon.