bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron-Stimulated Desorption of Positive Ions from Methanol Adsorbed on a Solid Ar Substrate
Authors: Kawanowa H. , Hanatani K. , Gotoh Y. , Souda R.
Published: July 2003

Electron-stimulated desorption (ESD) of positive ions from weakly physisorbed molecules has been investigated. From methanol adsorbed on a solid Ar substrate, the protonated cluster ions of the type H+(CH3OH) n(n = 1 - 4) are emitted, together with the fragment ions such as [Formula: see text](n = 0 - 3), H3O+, CHO+, CH3O+, etc. The yields of these ions are markedly enhanced at the smallest coverage and decay steeply with increasing coverage. Coulomb explosion between valence holes confined in adsorbed nanoclusters is responsible for the enhanced ion yields. Very few ions except for H+ are emitted from a thick layer as well as nanoclusters adsorbed directly on a metal substrate due to the delocalization of valence holes.
Modulated Phases on the FCC(110) Surfaces with Adsorbate-Induced Reconstructions
Authors: Kang Min , Kaburagi Makoto
Published: July 2003

We theoretically investigate the fcc(110) surfaces with missing row reconstructions induced by adatoms using the Blume–Emmery–Griffith (BEG) model. In the model, Kij is introduced to denote interactions between surface atoms and Jij to describe interactions between dipoles. The investigation by the mean field approximation has predicted that there appear modulated phases on the surfaces as the next-nearest-neighbor (NNN) and the nearest-neighbor (NN) interactions along the [001] direction become competitive. In this study, Monte Carlo simulations are performed to confirm the prediction. A correlation function defined by concentration operators in wave vector q space is calculated. The results show that the concentration modulations appear. The temperature versus the ratio of the NNN interaction K2 to the NN interaction K1 phase diagram is obtained. The possible features of the modulated phases in experiments are discussed.
On Strategy and Relative Skill in Poker
Authors: Dreef Marcel , Borm Peter , van der Genugten Ben
Published: July 2003

This article presents a generalization of the equilibrium analysis for the simple two-player poker game with alternate bidding of Von Neumann and Morgenstern. It approximates optimal play for this game if it is played with a regular deck of 52 cards and it discusses some strategic insights. In addition, the paper studies the relative skill level of this game.
A REVIEW OF FINGERPRINT IMAGE ENHANCEMENT METHODS
Authors: AILISTO HEIKKI , LINDHOLM MIKKO , TIKKANEN PAULI
Published: June 2003

Automatic fingerprint identification methods have become the most widely used technology in rapidly growing bioidentification applications. In this paper, different image enhancement approaches presented in the scientific literature are reviewed. Fingerprint verification can be divided into image acquisition, enhancement, feature extraction and matching steps. The enhancement step is needed to improve image quality prior to feature extraction. By far the most common approach relies on the filtering of the fingerprint images with filters adapted to local ridge orientation, but alternative approaches based on Fourier domain processing, direct ridge following and global features also exist. Methods of comparing the performance of enhancement methods are discussed. An example of the performance of different methods is given. Conclusions are made regarding the importance of effective enhancement, especially for noisy or low quality images.
A REMOTE AUTHENTICATION SYSTEM USING FINGERPRINTS
Authors: TICO MARIUS , KUOSMANEN PAULI
Published: June 2003

We present the design and implementation of a fingerprint-based remote authentication system. In this system, the fingerprint features captured at a client terminal are transmitted over a communication channel to a central server location where the verification takes place. In order to overcome replay attacks, we propose an original approach to fingerprint matching that relies on different fingerprint features for every execution of the authentication protocol. The paper also introduces an efficient approach for fingerprint image enhancement that constitutes the core of the feature extraction module included in the proposed authentication system. A public domain collection of fingerprint images is used to evaluate the system performance. The experimental results reveal that the proposed system can achieve good matching performance on this data collection and, furthermore, is able to accurately reject replay attacks.
VERIFICATION SPEED IN FINGERPRINT-BASED BIOMETRIC SYSTEMS
Authors: KONVALINKA IRA
Published: June 2003

Issues with verification speed improvement to fingerprint systems are investigated in this paper. First, the impact of verification speed on the overall system performance is highlighted. Then a rather general speed enhancement procedure for algorithms is proposed, consisting of two or more pattern matching stages for refining the value of the discrimination function. Special attention is paid to the algorithm supporting the verification procedure used to determine the two verification thresholds. It is shown, and supported by numerical examples, that significant verification speed improvement can be achieved without sacrificing the system accuracy.
A SYSTEM FOR HUMAN FACE AND FACIAL FEATURE LOCATION
Authors: MIAO JUN , LIU HONG , GAO WEN , ZHANG HONGMING , DENG GANG , CHEN XILIN
Published: June 2003

This paper presents an implementation of a system designed for the location of human faces and facial features such as pupils, eyes, nose and mouth. The kernel of the system is an integration of several algorithms, such as the human face center-of-gravity template, illumination compensation, and so on. A false-face removal algorithm is proposed in this paper specially for the distinguishing of cartoon faces from true faces. The testing experiments of the system have produced quite good results, with the average detection accuracy rates for face detection and facial feature location being 97.8% and 87.5% respectively.
A MODEL-BASED APPROACH TO HAIR REGION SEGMENTATION
Authors: LIU ZHI-QIANG , GUO JESSICA Y.
Published: June 2003

Hair regions represent an important external feature in many tasks involving the processing of human faces. Currently, the task of locating the hair region in a facial image requires manual intervention. In this paper we examine the different aspects of the hair region segmentation problem and develop an automatic system for such a problem. The system incorporates the human knowledge on where the hair is usually located in a facial image. Segmentation is performed via the classification of image pixels and is based on both textural and geometrical features. Experiments have shown that the segmentation results are generally satisfactory and are at least comparable to the performance of manual extraction.
DISCRIMINATORY SPARSE CODING AND ITS APPLICATION TO FACE RECOGNITION
Authors: SUN JUN , WANG WENYUAN , ZHUO QING , MA CHENGYUAN
Published: June 2003

Feature extraction is very important in the subject of pattern recognition. Sparse coding is an approach for extracting the independent features of an image. The image features extracted by sparse coding have led to better recognition performance as compared to those from traditional PCA-based methods. A new discriminatory sparse coding (DSC) algorithm is proposed in this paper to further improve the classification performance. Based on reinforcement learning, DSC encodes the training samples by individual class rather than by individual image as in sparse coding. Having done that it will produce a set of features with large and small intraclass variations, which is very suitable for recognition tasks. Experiments are performed on face image feature extraction and recognition. Compared with the traditional PCA- and ICA-based methods, DSC shows a much better recognition performance.
USING THE BETA-BINOMIAL DISTRIBUTION TO ASSESS PERFORMANCE OF A BIOMETRIC IDENTIFICATION DEVICE
Authors: SCHUCKERS MICHAEL E.
Published: June 2003

This paper discusses the use of the Beta-binomial distribution to estimate the matching performance of a biometric identification device. Specifically, the Beta-binomial distribution can be used to assess the variability in estimates of the false match and the false non-match rates when multiple users are tested more than once. This method accounts for the extraneous variability in this scenario and allows for the creation of confidence intervals under certain regularity conditions. The Beta-binomial differs from the binomial in that it models the extra-variation that is due to a lack of marginal independence among the observations. The Beta-binomial also has the flexibility to model the correlation of observations by the same individual that the binomial does not possess. This paper discusses maximum likelihood methodology for estimating the parameters of the Beta-binomial distribution. Finally, examples are given for simulated data that explicate this methodology.
STUDIES OF ARTERIAL INPUT IMPEDANCE IN MODELS OF CAROTID ARTERY
Authors: KAŁUŻYŃSKI K. , POWAŁOWSKI T. , LEŚNIAK B. , TRAWIŃSKI Z. , PAŁKO T. , LIEPSCH D.
Published: June 2003

A non-invasive method of measurement and analysis of the arterial input impedance of the carotid artery was applied to silicone models of the normal and stenosed carotid bifurcation. The experimental setup enabled the simulation of in vivo conditions. The experimental results were compared with impedance computed for a lumped element electrical model and a model containing transmission line elements. The stenosis resulted in increased impedance moduli and phase values. Similar phenomena were observed for both computational results. However, the transmission line model yielded phase plots closer to the experimental ones. The method of measurement and analysis of the arterial input impedance appears to be an efficient tool for the assessment of the properties of the carotid bifurcation.
EXPRESSION AND LOCATION OF VASP IN HUMAN ENDOTHELIAL CELLS: EFFECT OF A LAMINAR SHEAR STRESS
Authors: MULLER SYLVAINE , WEI LEI , LIU YUNGMING , LI KE , WANG XIONG , WANG BAOHA , OUYANG JINGPING , STOLTZ JEAN-FRANÇOIS
Published: June 2003

Recent elucidation of the primary VASP (vasodilator-simulated phosphoprotein) and identity of VASP binding proteins suggests that VASP is an important component of focal contacts which links signal transduction pathways and elements controlling cell motility. The aim of our study was to evaluate shear-stress-induced changes of VASP expression and localization in ECs. We showed, by western blotting measurements, that the shear stress involve some modifications on the expression of phosphorilated (50 kD) and non phosphorilated (46kD) VASP. Moreover, a fluorescence double-labeling shows the location of VASP on the actin fibers. At rest, ECs showed an array of microfilament bundles of the actin fibers and VASP were along their entire length. After exposure to shear stress, the stress fibers appeared and were oriented along with the flow. There were a thicker expression of VASP than in control, targeted to the ends of stress fibres. This seems to be an adjustment of the cells towards the mechanical stresses. These results suggest that VASP is a potential important component which participates in the regulation of cell actin remodelling induced by shear flow. VASP were involved in the mechano-transduction pathways.
INVESTIGATION OF GEOMETRY AND ATHEROSCLEROSIS IN THE HUMAN CAROTID BIFURCATIONS
Authors: GOUBERGRITS LEONID , AFFELD KLAUS , FERNANDEZ-BRITTO JOSE , FALCON LEONEL
Published: June 2003

The common carotid artery bifurcation has attracted a special interest because atherosclerotic wall alterations are often found in this artery and, because of its unique shape, which influences the flow field and, hence, the location of wall alterations. However, current knowledge of its geometry is insufficient by a determination and quantification of the "geometric risk factors". At post mortem the 86 arteries from sixty-four autopsy subjects were excised and filled with a special resin at the proper transmural pressure. Eighty-six vessel casts of the carotid artery were fabricated and some etiologic factors such as age, sex and disease were collected. Furthermore, the arteries were processed according to the methods established by the World Health Organization in 1958 and the locations and level of the atherosclerotic lesions (fatty streaks, fibrous and severe plaques) were assessed. The following selected geometric parameters of these arteries were measured: the diameters of the main branches of the carotid bifurcation (common, external and internal carotid arteries), the angles between these main branches, the enlargement of the carotid sinus and the enlargement of the carotid bifurcation. Furthermore, 26 vessel casts were digitized and three-dimensional computer models were generated. These models were than used to assess other geometrical features such as curvature of the branches and non-planarity of the bifurcation. The analysis of the relationship between measured geometric parameters, etiologic factors and atherosclerotic lesions was performed. The geometric parameters vary considerably, presumably contributing to a corresponding variability in the distribution and level of the atherosclerotic lesions and local hemodynamic.
NEW INSIGHTS INTO STRUCTURAL CHANGES OF LENS PROTEINS
Authors: REGINI J. W.
Published: June 2003

X-ray scattering techniques were used to study the effects of heating on whole eye lens and α-crystallin gels. The temperature range used was from 20 to 70°C. The position of single X-ray reflection seen in whole lens was unchanged in the temperature range 20 to 45°C, with a continuous spacing of 152 Å. However, at 50°C the spacing increased from 152 Å to 165 Å. An interpretation of these results is that in eye lens, α-crystallin is protecting other lens proteins from super-aggregation up to 50°C. In α-crystallin gels a moderate increase in both the spacing and intensity of the reflection was observed from 20 to 45°C, followed by a dramatic increase from 45 to 70°C. Over the whole temperature range the spacing changed from 138 Å at 70°C to 195 Å at 70°. After eleven hours of cooling, this effect was found to be irreversible.
CORNEAL TRANSPLANTATION AND THE ARTIFICIAL CORNEA
Authors: ALBON JULIE
Published: June 2003

The clinical need for an alternative to donor corneal tissue has encouraged much interest in recent years. An artificial cornea whether it be bio-engineered or a synthetic keratoprosthesis must fulfill the functions of the cornea it replaces: transparent, refractive surface, protection, non-immunogenic. A wide range of implants and biomedical devices have been developed in an attempt to correct corneal blindness. Limitation of existing biomaterials are evident when reviewing keratoprosthesis surgery complications. These include infection, intraocular inflammation, retromembrane formation, inadequate interface seal thus epithelial downgrowth and glaucoma. Attempts to improve healing in such cases have involved using various polymers or tissues to surround the optic. The successes and failures of synthetic prostheses that have been implanted in humans is discussed. More recently, the idea of a bio-engineered cornea has arisen. Tissue-engineering involves the manipulation of cells using in vitro techniques to create a composite tissue, which could then be implanted in vivo. Corneal equivalents have been reconstructed from corneal cell lines. They already have their potential uses in the biomedical world: as replacements for animals in toxicology testing and pharmacological studies, as well as in basic research into cell-cell and cell-matrix interactions of corneal wound healing. Current research is ongoing to determine if the bio-engineered cornea will have a role in corneal transplant surgery.
NOT ALL OSCILLATIONS ARE RUBBISH: FORWARD SIMULATION OF QUICK-RELEASE EXPERIMENTS
Authors: SIEBERT TOBIAS , WAGNER HEIKO , BLICKHAN REINHARD
Published: June 2003

Quick-release experiments often produce noticeable oscillations on the measured force and length data in the first few milliseconds after the force release. We measured oscillations in experiments with several species (Rattus norvegicus, Galea musteloides, Rana pipiens) and different experimental setups. These oscillations are generally ignored as artifacts.

This study investigates the cause of the oscillations. A biomechanical model of the experimental setup was developed consisting of a geometric model describing the setup and a Hill-type muscle-tendon model including the force-length-velocity relation and a linear spring in series. Muscle properties of each muscle were determined by the ISOFIT method. Model calculations and forward simulations of quick-release experiments based on experimentally determined muscle properties reveal that the observed oscillations are not artifacts (instrument and control), but the result of interactions of muscle-tendon properties with the inertia of muscles, bones and lever system.
FINITE ELEMENT SIMULATION OF IN VIVO TOOTH MOBILITY IN COMPARISON WITH EXPERIMENTAL RESULTS
Authors: DOROW CHRISTINA , SCHNEIDER JUERGEN , SANDER FRANZ G.
Published: June 2003

The objective of this study was to characterize the material properties of the periodontal ligament (PDL). Since the PDL undergoes the largest deformations when a load is applied to the tooth crown, its material properties mainly govern the resulting tooth deflection. By comparing experiments on tooth mobility with a Finite Element simulation using individual and realistic geometry models of the measured teeth, information about the mechanical properties of the PDL can be obtained. To investigate in vivo tooth mobility, a special experimental setup has been developed. The experimental results showed highly non-linear and time dependent material properties of tooth deflection as they are known for other soft biological tissues.6 Since in vivo tooth deflection is not an uniaxial tensional experiment, it is not possible to determine material parameters of the PDL. For this reason, a geometry model of the measured tooth was generated using computer tomography data and in a Finite Element simulation tooth deflection under external forces was calculated. A comparison of the simulation with the experimental data lead to an optimized characterization of the PDL in view of its mechanical properties.
INDUSTRIAL POLLUTION, ENVIRONMENTAL SUFFERING AND POLICY MEASURES: AN INDEX OF ENVIRONMENTAL SENSITIVITY PERFORMANCE (IESP)
Authors: CAGATAY SELIM , MIHCI HAKAN
Published: June 2003

An index of environmental sensitivity performance (IESP) is constructed in order to measure and quantify the comparative environmental sensitivity of countries. The main emphasis of IESP is to obtain an overall measure of sensitiveness instead of focusing on various indicators designed for particular environmental issues. The sub-indices, however, can also be utilised for specific environmental concerns. IESP is built to analyse empirically certain economic relationships that appeared firstly in the emergence of environmental regulations in industrial nations and secondly, in the debate over recent international agreements.

The main findings of the IESP seem to be consistent with the disputes emphasising the growing sensitivity of the developed nations towards the industrial pollution relative to the developing nations. With a very few exceptions, developed countries appear to be stringent in the pursuit of the industrial environmental regulations. This general trend, which is consistent with the theoretical expectations, contributes to the value of the IESP as a quantitative instrument. Furthermore, the wider range of the countries' index values can be considered as promising in terms of utilising IESP in quantitative applications.
AUDITING STRATEGIC ENVIRONMENTAL ASSESSMENT PRACTICE IN CANADA
Authors: NOBLE BRAM F.
Published: June 2003

Strategic environmental assessment (SEA) is taking place in diverse forms, and SEA requirements vary considerably from one nation to the next. While the true measure of effectiveness of SEA is its influence on decision output and policy, plan and program (PPP) outcomes, an effective SEA requires a quality assessment process. This paper suggests that there is no generic set of audit criteria that is appropriate for evaluating the quality of all SEA applications. Auditing SEA quality performance requires criteria that reflect the guidelines and procedural requirements of the institutional arrangements within which SEA is practised. Based on a proposed set of SEA quality performance criteria for Canada, this paper presents the findings of an audit of five national-level Canadian SEA applications.
A VALUE-FOCUSED THINKING APPROACH FOR THE ENVIRONMENTAL MANAGEMENT OF BUILDINGS CONSTRUCTION
Authors: HASSAN OSAMA A. B.
Published: June 2003

This paper attempts to adapt the value-focused thinking approach to the decision problems in the field of environmental management of buildings construction. A qualitative value model based on the results of life cycle assessment is presented. The model is applied on a case study in which a decision should be made on three types of roof structures: wood, steel and concrete. It is found that the roof structure made of wood is the most compatible option with respect to the environmental requirements of buildings construction. Thus, the value-focused thinking model can be used in different situations to analyze what management actions will be most effective to maximise the fulfillment of the environmental requirements of building standards.
Spectral inclusions and stability results for strongly continuous semigroups
Authors: Elkoutri Abdelkader , Taoudi Mohamed Aziz
Published: July 2003

We prove some spectral inclusions for strongly continuous semigroups. Some stability results are also established.
Cm solutions of systems of finite difference equations
Authors: Liu Xinhe , Zhao Xiuli , Ma Jianmin
Published: July 2003

Let ℝ be the real number axis. Suppose that G, H are Cm maps from ℝ2n+3 to ℝ. In this note, we discuss the system of finite difference equations G(x, f(x), f(x + 1), …, f(x + n), g(x), g(x + 1), …, g(x + n)) + 0 and H(x, g(x), g(x + 1), …, g(x + n), f(x), f(x + 1), …, f(x + n)) = 0 for all x ∈ ℝ, and give some relatively weak conditions for the above system of equations to have unique Cm solutions (m ≥ 0).
On an equivalence of fuzzy subgroups III
Authors: Murali V. , Makamba B. B.
Published: July 2003

This paper is the third in a series of papers studying equivalence classes of fuzzy subgroups of a given group under a suitable equivalence relation. We introduce the notion of a pinned flag in order to study the operations sum, intersection and union, and their behavior with respect to the equivalence. Further, we investigate the extent to which a homomorphism preserves the equivalence. Whenever the equivalences are not preserved, we have provided suitable counterexamples.
The spectrum of a class of almost periodic operators
Authors: Riedel Norbert
Published: July 2003

For almost Mathieu operators, it is shown that the occurrence of Cantor spectrum and the existence, for every point in the spectrum and suitable phase parameters, of at least one localized
eigenfunction which decays exponentially are inconsistent properties.
The hull number of an oriented graph
Authors: Chartrand Gary , Fink John Frederick , Zhang Ping
Published: July 2003

We present characterizations of connected graphs G of order n ≥ 2 for which h+(G) = n. It is shown that for every two integers n and m with , there exists a connected graph G of order n and size m such that for each integer k with 2 ≤ k ≤ n, there exists an orientation of G with hull number G.
On the Fresnel sine integral and the convolution
Authors: Kılıçman Adem
Published: July 2003

The Fresnel sine integral S(x), the Fresnel cosine integral C(x), and the associated functions S+(x),  S−(x),  C+(x), and C−(x) are defined as locally summable functions on the real line. Some convolutions and neutrix convolutions of the Fresnel sine integral and its associated functions with are evaluated.
Estimates for the Green function and singular solutions for polyharmonic nonlinear equation
Authors: Bachar Imed , Màagli Habib , Masmoudi Syrine , Zribi Malek
Published: July 2003

We establish a new form of the 3G theorem for polyharmonic Green function on the unit ball of ℝn(n ≥ 2) corresponding to zero Dirichlet boundary conditions. This enables us to introduce a new class of functions Km,n containing properly the classical Kato class Kn. We exploit properties of functions belonging to Km,n to prove an infinite existence result of singular positive solutions for nonlinear elliptic equation of order 2m.
Feedback stabilization of semilinear heat equations
Authors: Barbu V. , Wang G.
Published: July 2003

This paper is concerned with the internal and boundary stabilization of the steady‐state solutions to quasilinear heat equations via internal linear feedback controllers provided by an LQ control problem associated with the linearized equation.
Approximation structures and applications to evolution equations
Authors: Duma Adrian , Vladimirescu Cristian
Published: July 2003

We discuss various properties of the nonlinear A‐proper operators as well as a generalized Leray‐Schauder principle. Also, a method of approximating arbitrary continuous operators by A‐proper mappings is described. We construct, via appropriate Browder‐Petryshyn approximation schemes, approximative solutions for linear evolution equations in Banach spaces.
Identifying generalized Fitzhugh‐Nagumo equation from a numerical solution of Hodgkin‐Huxley model
Authors: Georgiev Nikola V.
Published: July 2003

An analytic time series in the form of numerical solution (in an appropriate finite time interval) of the Hodgkin‐Huxley current clamped (HHCC) system of four differential equations, well known in the neurophysiology as an exact empirical model of excitation of a giant axon of Loligo, is presented. Then we search for a second‐order differential equation of generalized Fitzhugh‐Nagumo (GFN) type, having as a solution the given single component (action potential) of the numerical solution. The given time series is used as a basis for reconstructing orders, powers, and coefficients of the polynomial right‐hand sides of GFN equation approximately governing the process of action potential. For this purpose, a new geometrical method for determining phase space dimension of the unknown dynamical system (GFN equation) and a specific modification of least squares method for identifying unknown coefficients are developed and applied.
Large diffusivity finite‐dimensional asymptotic behaviour of a semilinear wave equation
Authors: Willie Robert
Published: July 2003

We study the effects of large diffusivity in all parts of the domain in a linearly damped wave equation subject to standard zero Robin‐type boundary conditions. In the linear case, we show
in a given sense that the asymptotic behaviour of solutions verifies a second‐order ordinary differential equation. In the semilinear case, under suitable dissipative assumptions on the nonlinear term, we prove the existence of a global attractor for fixed diffusion and that the limiting attractor for large diffusion is finite dimensional.
Variational analysis for simulating free‐surface flows in a porous medium
Authors: Ahmed Shabbir , Collins Charles
Published: July 2003

A variational formulation has been developed to solve a parabolic partial differential equation describing free‐surface flows in a porous medium. The variational finite element method
is used to obtain a discrete form of equations for a two‐dimensional domain. The matrix characteristics and the stability criteria have been investigated to develop a stable numerical algorithm for solving the governing equation. A computer programme has been written to solve a symmetric positive definite system obtained from the variational finite element analysis. The system of equations is solved using the conjugate gradient method. The solution generates time‐varying hydraulic heads in the subsurface. The interfacing free surface between the unsaturated and saturated zones in the variably saturated domain is located, based on the computed hydraulic heads. Example problems are investigated. The finite element solutions are compared with the exact solutions for the example problems. The numerical characteristics of the finite element solution method are also investigated using the example problems.
Aspirin Protects Endothelial Cells From Oxidant Damage Via the Nitric Oxide-cGMP Pathway
Authors: Grosser Nina , Schröder Henning
Published: July 2003

Objectives—

Aspirin is known to exert cytoprotection by presently unidentified mechanisms. This study investigates the involvement of nitric oxide (NO) in antioxidant cellular protection induced by aspirin.

Methods and Results—

A 24-hour incubation with hydrogen peroxide markedly reduced viability of cultured endothelial cells. Preincubation with aspirin (3 to 30 μmol/L) protected endothelial cells from hydrogen peroxide–mediated toxicity and increased viability in a concentration-dependent fashion by up to 95% of control. This effect was specific in that other nonsteroidal anti-inflammatory drugs, such as salicylate or indomethacin, did not alter hydrogen peroxide toxicity. Aspirin-induced endothelial protection was abrogated in the presence of the NO scavenger PTIO (30 μmol/L) and the inhibitor of soluble guanylyl cyclase ODQ (1 μmol/L). Moreover, the
l
-arginine antagonist L-NMMA (25 μmol/L), but not its D-enantiomer, led to complete inhibition of aspirin-dependent cytoprotection. Correspondingly, aspirin enhanced NO synthase activity (citrulline formation) and intracellular cyclic GMP accumulation in endothelial cells. Protein expression of endothelial NO synthase remained unaffected in the presence of aspirin.

Conclusions—

Our data suggest that endothelial NO synthase is a site of action of aspirin and that the NO/cyclic GMP system assumes a crucial function in mediating the cytoprotective action of aspirin.
Effect of Hyperhomocystinemia and Hypertension on Endothelial Function in Methylenetetrahydrofolate Reductase–Deficient Mice
Authors: Virdis Agostino , Iglarz Marc , Neves Mario Fritsch , Amiri Farhad , Touyz Rhian M. , Rozen Rima , Schiffrin Ernesto L.
Published: July 2003

Objective—

We evaluated the effect of hyperhomocystinemia and angiotensin (Ang) II on vascular function and structure in methylenetetrahydrofolate reductase knockout mice (
Mthfr
+/−
).

Methods and Results—

Mthfr
+/−
and controls (
Mthfr
+/+
) received Ang II (400 ng/kg per min SC) or saline (14 days). Blood pressure, similar in
Mthfr
+/−
and
Mthfr
+/+
, was increased by Ang II. Acetylcholine- and bradykinin-induced relaxations were impaired in mesenteric resistance arteries (pressurized myograph) in
Mthfr
+/−
and in Ang II–infused
Mthfr
+/+
mice and additionally blunted in Ang II–infused
Mthfr
+/−
mice. The inhibition by L-NAME on acetylcholine was reduced in
Mthfr
+/−
and in Ang II–
Mthfr
+/+
and absent in Ang II–
Mthfr
+/−
mice. In these groups, vitamin C improved the response to acetylcholine and restored the inhibition by L-NAME. The media to lumen ratio of small arteries, similar in
Mthfr
+/−
and
Mthfr
+/+
, was increased by Ang II. Vascular NADPH oxidase activity, similar in
Mthfr
+/−
and
Mthfr
+/+
, increased after Ang II infusion. Vascular xanthine oxidase activity was also similar in
Mthfr
+/−
and
Mthfr
+/+
. Superoxide production in the aorta was reduced by sepiapterin and by L-NAME, suggesting that reduced bioavailability of tetrahydrobiopterin and uncoupling of nitric oxide synthase were the origin of increased reactive oxygen species in this model.

Conclusions—

Mthfr
+/−
mice show endothelial dysfunction of mesenteric vessels probably attributable to a reduced nitric oxide bioavailability caused by oxidative excess due to uncoupling of nitric oxide synthase without vascular structural alterations. Concurrent Ang II–induced hypertension additionally reduced nitric oxide, increased NADPH oxidase activity, and induced structural alterations. Our findings suggest additive adverse effect of Ang II–dependent hypertension and hyperhomocystinemia on endothelial function.
Influence of Hypertension on Early Carotid Artery Remodeling
Authors: Chironi Gilles , Gariepy Jerome , Denarie Nicolas , Balice Maria , Megnien Jean-Louis , Levenson Jaime , Simon Alain
Published: July 2003

Objectives—

We aimed to analyze the influence of hypertension on early large artery remodeling.

Methods and Results—

Carotid intima-media thickness (IMT) and diameter were measured ultrasonographically in 394 normotensive subjects and 327 untreated and 528 treated hypertensive patients. IMT and diameter were increased in hypertensive groups, treated or untreated, compared with the normotensive group (
P
<0.001). Positive association existed between diameter and IMT in the overall study population (
P
<0.001), and this association interacted with the category of clinical groups (
P
<0.01). The slope of the diameter-IMT relationship was different between normotensive, untreated hypertensive, and treated hypertensive groups (
P
<0.01), with higher value in the treated hypertensive group than in untreated hypertensive and normotensive groups (
P
<0.05,
P
<0.01). Adjustment for blood pressure, lipid-lowering therapy, or multiple covariates (age, sex, systolic and diastolic blood pressures, body mass index, lipid-lowering therapy, smoking, and previous cardiovascular disease) did not abolish the diameter-IMT slope difference between clinical groups (
P
<0.01).

Conclusions—

The sensitivity of carotid artery enlargement in response to increase in wall thickness was unchanged in untreated hypertension but altered by antihypertensive therapy compared with the normotensive condition.
Scavenger Receptor Class B Type I–Mediated Protection Against Atherosclerosis in LDL Receptor–Negative Mice Involves Its Expression in Bone Marrow–Derived Cells
Authors: Covey Scott D. , Krieger Monty , Wang Wei , Penman Marsha , Trigatti Bernardo L.
Published: July 2003

Objective—

Scavenger receptor class B type I (SR-BI) is a cell-surface HDL receptor that is implicated in reverse cholesterol transport and protection against atherosclerosis. We have previously demonstrated that SR-BI/apolipoprotein E double-knockout mice develop severe occlusive coronary artery disease and myocardial infarction and die at ≈6 weeks of age. To determine if this is a general effect of a lack of SR-BI, we generated mice deficient in both SR-BI and the LDL receptor.

Methods and Results—

Complete ablation of SR-BI expression in LDL receptor knockout mice resulted in increased plasma cholesterol associated with HDL particles of abnormally large size and a 6-fold increase in diet-induced aortic atherosclerosis but no macroscopic evidence of early-onset coronary artery disease, cardiac pathology, or early death. Furthermore, selective elimination of SR-BI expression in bone marrow–derived cells resulted in increased diet-induced atherosclerosis in LDL receptor knockout mice without concomitant alterations in the distributions of plasma lipoprotein cholesterol.

Conclusions—

SR-BI expression protects against atherosclerosis in LDL receptor–deficient as well as apolipoprotein E–deficient mice, and its expression in bone marrow–derived cells contributes to this protection.
Reduced Expression of Endothelial Connexin37 and Connexin40 in Hyperlipidemic Mice
Authors: Yeh Hung-I , Lu Chi-Sheng , Wu Yih-Jer , Chen Chih-Chun , Hong Ray-Ching , Ko Yu-Shien , Shiao Ming-Shi , Severs Nicholas J. , Tsai Cheng-Ho
Published: July 2003

Objective—

We sought to clarify the response of endothelial connexins to hyperlipidemia and lipid-lowering therapy.

Methods and Results—

Aortic endothelial gap junctions were analyzed by en face immunoconfocal microscopy and electron microscopy in C57BL/6 mice subjected to the following regimens: (1) normal chow (NC) for 3 months (3 mo), (2) NC for 9 mo, (3) NC for 3 mo, followed by a cholesterol-enriched diet (CED) for 6 mo, (4) NC for 3 mo and CED for 6 mo, with simvastatin in the final week, and (5) (in apoprotein E [apoE]-deficient mice) NC and examined at 3 mo and 7 to 9 mo. In wild-type mice, connexin37 (Cx37) and Cx40 were markedly downregulated in the CED-fed animals compared with those fed NC (CED vs 9-mo NC, 77% reduction in Cx37 and 65% reduction in Cx40; both
P
<0.01). After simvastatin treatment, Cx40 remained depressed, but Cx37 recovered to 94% of the level found in non–cholesterol-fed animals (
P
<0.01). Electron microscopy demonstrated that gap junctions were smaller in animals fed the CED compared with those given simvastatin and with controls fed NC (
P
<0.01). Endothelial connexins were rare in the atherosclerotic plaques of apoE-deficient mice.

Conclusions—

Mouse aortic endothelial gap junctions and connexins are downregulated during long-term hyperlipidemia. Short-term treatment with simvastatin leads to recovery of Cx37 expression but not Cx40 expression.
Therapeutic Induction of Arteriogenesis in Hypoperfused Rat Brain Via Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Buschmann Ivo R. , Busch Hans-Jörg , Mies Günter , Hossmann Konstantin-Alexander
Published: July 2003

Background—

Colony-stimulating factors (CSFs) have been shown to effectively induce arteriogenesis in the hindlimb. Moreover, clinical trials demonstrated positive effects of CSFs on arteriogenesis in patients with coronary artery disease. However, patients with cerebrovascular disease have not yet profited from treatments aimed at the growth of brain vessels. Thus far, angiogenesis studies have failed to demonstrate improvement of stroke outcome. Arteriogenesis differs from angiogenesis in that it substitutes arterial collaterals for the occluded artery.

Methods and Results—

We tested in a novel brain arteriogenesis rat model (occlusion of vertebral plus left carotid artery [3-VO]) the application of CSFs or saline over 7 or 21 days. On 3-VO postmortem, latex perfusion demonstrated a time- and treatment-dependent arteriogenesis of the posterior cerebral artery (PCA). In saline-treated animals, the PCA diameter increased by 39%; in granulocyte-macrophage (GM)-CSF-treated animals, this increase was significantly faster (72% after 1 week). Functionally, saline-treated animals exhibited a decline of CO
2
reactivity (mm Hg) from 1.48% to 0.1% compared with GM-CSF–treated animals (1.43% arterial pC
o
2
change after 1 week). This difference remained significant after 3 weeks. This functional improvement correlated with increased numbers of CD68-positive macrophages in histological sections of the PCA in GM-CSF–treated animals and only a few macrophages in saline-treated animals.

Conclusions—

To the best of our knowledge, this is the first report of stimulation of arteriogenesis in the brain. The subcutaneous application of GM-CSF led to functional improvement of brain hemodynamic parameters.
Glycosyl Phosphatidylinositol Anchorage of Tissue Factor Pathway Inhibitor
Authors: Zhang Jing , Piro Orlando , Lu Lan , Broze George J.
Published: July 2003

Background—

The endothelium is a major source of tissue factor pathway inhibitor (TFPI), the endogenous regulator of TF-induced coagulation, and a significant proportion of the expressed TFPI remains associated with the endothelial surface.

Methods and Results—

Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment reduced TFPI at the surface of cultured endothelial cells by ≈80%, and at least a portion of the TFPI released by PI-PLC contained an intrinsic glycosylphosphatidylinositol (GPI) anchor that is recognized by anti-crossreactive determinant antibodies. Endothelial cells express both of the alternatively spliced forms of TFPI mRNA at a ratio of TFPIβ/TFPIα mRNA of ≈0.1 to 0.2. In Chinese hamster ovary (CHO) cells, TFPIα is predominantly secreted, whereas TFPIβ is a GPI-anchored membrane protein. Like TFPIβ, the small proportion of the TFPIα expressed by CHO cells that remains surface associated is also released by PI-PLC treatment, suggesting that it is bound to a separate GPI-anchored protein(s) at the surface of the cells.

Conclusions—

Both direct (TFPIβ) and indirect (TFPIα) GPI-mediated membrane anchorage is involved in localizing TFPI to the surface of cells.
Detection of Atherosclerotic Plaque With Gadofluorine-Enhanced Magnetic Resonance Imaging
Authors: Barkhausen Jörg , Ebert Wolfgang , Heyer Claudia , Debatin Jörg F. , Weinmann Hanns-Joachim
Published: July 2003

Background—

The purpose of this study was to visualize atherosclerotic plaques independently of luminal narrowing using T
1
-weighted contrast-enhanced MRI.

Methods and Results—

Eight Watanabe heritable hyperlipidemic (WHHL) rabbits, aged 9 to 18 months, and 8 age-matched controls (New Zealand White rabbits) underwent MRI of the aortic arch before and up to 48 hours after injection of 100 μmol/kg Gadofluorine (Schering AG). Additionally, 8 WHHL rabbits were examined with Magnevist (Schering AG). A half-Fourier acquisition single-shot turbo-spin-echo (HASTE) sequence and a T
1
-weighted inversion-recovery turbo fast, low-angle shot sequence were used for data acquisition. Immediately after the MR examination, the animals were killed, the aorta was stained with Sudan red, and ex vivo imaging of the stained aortic specimens was performed. Additionally, gadolinium concentrations in plaque (Sudan-positive) and normal (Sudan-negative) aortic wall segments were measured. Plain MR imaging revealed no plaques in the aortic arch in either animal group. Enhancement occurred in the aortic wall of all WHHL rabbits examined with Gadofluorine but not in the vessel wall of animals examined with Magnevist and the control group. Sudan red staining demonstrated multiple plaques in the aortic arch of all WHHL rabbits. Ex vivo imaging demonstrated that the area of hyperenhancement matched the area of plaques stained with Sudan red. The gadolinium concentration was 7±5 nmol/g for normal aortic wall of the control group and 368±30 nmol/g for aortic wall with plaque in WHHL.

Conclusions—

Gadofluorine enhances the imaging of atherosclerotic plaques and enables improved plaque detection of even nonstenotic lesions that are not visible on unenhanced MRI.
Mechanosensitive p27
Kip1
Regulation and Cell Cycle Entry in Vascular Smooth Muscle Cells
Authors: Sedding Daniel G. , Seay Ulrike , Fink Ludger , Heil Matthias , Kummer Wolfgang , Tillmanns Harald , Braun-Dullaeus Ruediger C.
Published: July 2003

Background—

Cyclic stretch plays an important role in the homeostasis of vessel structure. Increased forces might, however, contribute to remodeling processes, resulting in vascular proliferative diseases. The initial molecular events necessary for mechanosensitive cell cycle entry of quiescent smooth muscle cells are poorly understood.

Methods and Results—

In this study, we demonstrate that mechanical strain resulted in a rapid, integrin-dependent but mitogen-independent activation of phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt) in quiescent vascular smooth muscle cells. Subsequently, downstream ALL 1 fused gene from chromosome X (AFX)-like forkhead transcription factors were inactivated, leading to transcriptional downregulation of p27
Kip1
. This contrasted with the posttranscriptional protein reduction of p27
Kip1
in cells stimulated with serum mitogens. Stretch-mediated p27
Kip1
downregulation was accompanied by activation of cyclin-dependent kinase 2, hyperphosphorylation of retinoblastoma protein, and proliferation. Forkhead transcription factor inactivation and p27
Kip1
downregulation were prevented by the PI3-K inhibitors wortmannin and LY294002. Pharmacological blockade of other kinases, such as p42/44, p38, and protein kinase A or C, did not influence the mechanosensitive gene regulation. p27
Kip1
downregulation and cell cycle entry were, however, prevented by overexpression of a constitutively inactive form of Akt or constitutively active forms of forkhead transcription factors.

Conclusions—

Our data demonstrate that the earliest cell cycle events can occur in a solely mechanosensitive fashion. Vascular smooth muscle cells are, furthermore, able to use transcriptional or posttranscriptional mechanisms to regulate p27
Kip1
, depending on the stimulus to which they are exposed. This observation has novel implications for understanding of vascular proliferative diseases.
Surface Electrocardiographic Characteristics of Right and Left Atrial Flutter
Authors: Bochoeyer Andres , Yang Yanfei , Cheng Jie , Lee Randall J. , Keung Edmund C. , Marrouche Nassir F. , Natale Andrea , Scheinman Melvin M.
Published: July 2003

Background—

There is little information about the surface expression of non-cavotricuspid isthmus (CTI)-dependent right atrial (RA) or left atrial (LA) flutter circuits.

Methods and Results—

We retrospectively evaluated 32 episodes (in 26 patients) of atypical RA and 22 episodes (in 21 patients) of LA flutter. The surface ECG of 13 patients with lower-loop reentry was similar to that of their pattern during counterclockwise (CCW) CTI atrial flutter (AFL), except for decreased amplitude of the terminal forces in the inferior leads. In 11 of 24 episodes characterized by high or multiple breaks over the crista, the ECG showed changes that depended on the initial activation sequence of the LA. In 7 of 8 episodes of upper-loop reentry, the ECG pattern completely mimicked that for clockwise (CW) CTI AFL. All 11 patients with an LA septal circuit showed a typical ECG pattern characterized by prominent forces in lead V
1
with flat deflections in the other surface leads. Eleven patients with other LA circuits had a more variable pattern but showed decreased voltage in the inferior leads compared with that of a group with CCW-CTI AFL (1.6±1 vs 2.68±0.7 mV, respectively;
P
<0.05).

Conclusions—

The RA surface-ECG patterns different from those of CCW or CW-CTI could still be CTI dependent. In contrast, a typical CW-CTI surface pattern was always seen in patients with upper-loop reentry, which was non-CTI dependent. LA AFL circuits had either flat or low-amplitude forces in the inferior leads.
Hybrid Cell–Gene Therapy for Pulmonary Hypertension Based on Phagocytosing Action of Endothelial Progenitor Cells
Authors: Nagaya Noritoshi , Kangawa Kenji , Kanda Munetake , Uematsu Masaaki , Horio Takeshi , Fukuyama Naoto , Hino Jun , Harada-Shiba Mariko , Okumura Hiroyuki , Tabata Yasuhiko , Mochizuki Naoki , Chiba Yoshihide , Nishioka Keisuke , Miyatake Kunio , Asahara Takayuki , Hara Hiroshi , Mori Hidezo
Published: July 2003

Background—

Circulating endothelial progenitor cells (EPCs) migrate to injured vascular endothelium and differentiate into mature endothelial cells. We investigated whether transplantation of vasodilator gene-transduced EPCs ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats.

Methods and Results—

We obtained EPCs from cultured human umbilical cord blood mononuclear cells and constructed plasmid DNA of adrenomedullin (AM), a potent vasodilator peptide. We used cationic gelatin to produce ionically linked DNA-gelatin complexes. Interestingly, EPCs phagocytosed plasmid DNA-gelatin complexes, which allowed nonviral, highly efficient gene transfer into EPCs. Intravenously administered EPCs were incorporated into the pulmonary vasculature of immunodeficient nude rats given MCT. Transplantation of EPCs alone modestly attenuated MCT-induced pulmonary hypertension (16% decrease in pulmonary vascular resistance). Furthermore, transplantation of AM DNA-transduced EPCs markedly ameliorated pulmonary hypertension in MCT rats (39% decrease in pulmonary vascular resistance). MCT rats transplanted with AM-expressing EPCs had a significantly higher survival rate than those given culture medium or EPCs alone.

Conclusions—

Umbilical cord blood–derived EPCs had a phagocytosing action that allowed nonviral, highly efficient gene transfer into EPCs. Transplantation of AM gene-transduced EPCs caused significantly greater improvement in pulmonary hypertension in MCT rats than transplantation of EPCs alone. Thus, a novel hybrid cell–gene therapy based on the phagocytosing action of EPCs may be a new therapeutic strategy for the treatment of pulmonary hypertension.