bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting Middle School Mathematics to Computer Vision and Pattern Recognition
Authors: Tanimoto Steven L.
Published: July 2003

The subject matter of computer vision and pattern recognition can play a useful role in the education of mathematics for students in middle school. New standards in education call for new content relevant to students' lives, and new pedagogical methods involving construction, group work, discovery, and the use of new technology. The project "Mathematics Experiences Through Image Processing" at the University of Washington has developed software and learning activities that enable middle school and high school students to use mathematical tools and concepts to explore some exciting ideas of image processing. This paper describes these materials and discusses how the ideas of computer vision and pattern recognition can be integrated into the curriculum. Not only do we use 2D topics such as digital geometry and edge detection, but also 3D topics such as surface construction and stereogram generation.
Integrating Image Computation in Undergraduate Level Data-Structure Education
Authors: Sarkar Sudeep , Goldgof Dmitry
Published: July 2003

There is a growing need for expertise both in image analysis and in software engineering. To date, these two areas have been taught separately in an undergraduate computer and information science curriculum. However, we have found that introduction to image analysis can be easily integrated in data-structure courses without detracting from the original goal of teaching data structures. Some of the image processing tasks offer a natural way to introduce basic data structures such as arrays, queues, stacks, trees and hash tables. Not only does this integrated strategy expose the students to image related manipulations at an early stage of the curriculum but it also imparts cohesiveness to the data-structure assignments and brings them closer to real life. In this paper we present a set of programming assignments that integrates undergraduate data-structure education with image processing tasks. These assignments can be incorporated in existing data-structure courses with low time and software overheads. We have used these assignment sets thrice: once in a 10-week duration data-structure course at the University of California, Santa Barbara and the other two times in 15-week duration courses at the University of South Florida, Tampa.
Interactive Textbooks; Embedding Image Processing Operator Demonstrations in Text
Authors: Fisher Robert B. , Koryllos Konstantinos
Published: July 2003

Traditional image processing teaching has used materials where the theory and drill are separated into textbooks and image processing packages. HTML and JAVA might allow easier construction of an integrated teaching resource. Such a resource would have widespread, platform-independent accessibility. This paper reports our assessment of this potential, which is explored through extensions of the HIPR teaching materials. Our conclusions are that the approach is feasible and attractive to students, that a few standard programming protocols reduce development time, and that use of compiled JAVA is essential.
Augmenting Platform-Based Design with Synthesis Tools
Authors: Xie Yuan , Xu Jiang , Wolf Wayne
Published: July 2003

Platform-based design faces an essential tension: it wants to reuse previous designs to leverage IP; but new designs must necessarily include work that is not complete or well-characterized. Synthesis and analysis methods are therefore important elements in platform-based design methodologies. This paper describes two aspects of this problem. First, we consider the first-generation dilemma, in which we must use additional analysis in order to create the first generation of a platform. Second, we describe a synthesis method that creates accelerators for platforms whose clock periods have been optimized for the system characteristics.
Some Aspects of the Test Generation Problem for an Application-Oriented Test of SRAM-Based FPGAs
Authors: Renovell M.
Published: July 2003

This paper presents a structural approach for testing SRAM-based FPGAs taking into account the configurability of such flexible devices. When SRAM-based FPGA testing is considered, different situations have first to be identified: namely the Application-Oriented Test situation and the Manufacturing-Oriented Test situation. This paper concentrates on Test Pattern Generation and DFT for an Application-Oriented test of SRAM-based FPGAs.
A Low-Power Design for Reed–Solomon Decoders
Authors: Chang Hsie-Chia , Lee Chen-Yi
Published: July 2003

In this paper, a low-power design for the Reed–Solomon (RS) decoder is presented. Our approach includes a novel two-stage syndrome calculator that reduces the syndrome computations by one-half, a modified Berlekamp–Massey algorithm in the key equation solver and a terminated mechanism in the Chien search circuit. The test chip for (255,239) and (208,192) RS decoders are implemented by 0.25 μm CMOS 1P5M and 0.35 μm CMOS SPQM standard cells, respectively. Simulation results show our approach can work successfully and achieved large reduction of power consumption on the average.
Simulink-Based Codesign and Cosimulation of a Common Rail™ Injector Test Bench
Authors: Reyneri L. M. , Bellei E. , Bussolino E. , Gregoretti F. , Mari L. , Renga F.
Published: July 2003

This paper describes how a complete test bench for a Common Rail™ injection system has been built by means of hardware/software codesign techniques. The test bench is made up of two main components: a HW component running mainly on a FPGA device, interacting directly with the electromechanical components (namely, a high pressure pump, six electrical injectors, an electrical discharge valve, two pressure sensors), for high speed signal acquisition and generation, and for closed loop control; and a SW component, written in Visual Basic™, running on a PC, including a graphical user interface for parameters setting and system characterization. An additional signal acquisition board is also used for monitoring six load cells and for temperature control. The two components communicate through the standard PC's parallel port operated in Enhanced Parallel Port mode. The test bench is totally designed, simulated and implemented under the CodeSimulink hardware/software codesign environment, which runs as a plug-in of The Mathworks™ Simulink™ design tool. A few other commercial HW/SW codesign tools have also been considered, but none of them offered either enough performance or flexibility or, more importantly, ease of use and compatibility with existing Simulink simulation models of the various components of the test bench.
A Hardware–Software System for Tomographic Reconstruction
Authors: Müller Jan , Fimmel Dirk , Merker Renate , Schaffer Rainer
Published: July 2003

We present the design of a hardware–software system for the reconstruction of tomographic images. In a systematic approach we developed the parallel processor array, a reconfigurable hardware controller and processing kernel, and the software control up to the integration into a graphical user interface. The processor array acting as a hardware accelerator, is constructed using theoretical results and methods of application-specific hardware design. The reconfigurability of the system allows one to utilize a much wider realm of algorithms than the three reconstruction algorithms implemented so far. In the paper we discuss the system design at different levels from algorithm transformations to board development.
Computation of Periodic Solutions of Conservative Systems with Application to the 3-Body Problem
Authors: Doedel E. J. , Paffenroth R. C. , Keller H. B. , Dichmann D. J. , Galán-Vioque J. , Vanderbauwhede A.
Published: July 2003

We show how to compute families of periodic solutions of conservative systems with two-point boundary value problem continuation software. The computations include detection of bifurcations and corresponding branch switching. A simple example is used to illustrate the main idea. Thereafter we compute families of periodic solutions of the circular restricted 3-body problem. We also continue the figure-8 orbit recently discovered by Chenciner and Montgomery, and numerically computed by Simó, as the mass of one of the bodies is allowed to vary. In particular, we show how the invariances (phase-shift, scaling law, and x, y, z translations and rotations) can be dealt with. Our numerical results show, among other things, that there exists a continuous path of periodic solutions from the figure-8 orbit to a periodic solution of the restricted 3-body problem.
Recent Developments in Chaotic Time Series Analysis
Authors: Lai Ying-Cheng , Ye Nong
Published: July 2003

In this paper, two issues are addressed: (1) the applicability of the delay-coordinate embedding method to transient chaotic time series analysis, and (2) the Hilbert transform methodology for chaotic signal processing.

A common practice in chaotic time series analysis has been to reconstruct the phase space by utilizing the delay-coordinate embedding technique, and then to compute dynamical invariant quantities of interest such as unstable periodic orbits, the fractal dimension of the underlying chaotic set, and its Lyapunov spectrum. As a large body of literature exists on applying the technique to time series from chaotic attractors, a relatively unexplored issue is its applicability to dynamical systems that exhibit transient chaos. Our focus will be on the analysis of transient chaotic time series. We will argue and provide numerical support that the current delay-coordinate embedding techniques for extracting unstable periodic orbits, for estimating the fractal dimension, and for computing the Lyapunov exponents can be readily adapted to transient chaotic time series.

A technique that is gaining an increasing attention is the Hilbert transform method for signal processing in nonlinear systems. The general goal of the Hilbert method is to assess the spectrum of the instantaneous frequency associated with the underlying dynamical process. To obtain physically meaningful results, it is necessary for the signal to possess a proper rotational structure in the complex plane of the analytic signal constructed by the original signal and its Hilbert transform. We will describe a recent decomposition procedure for this task and apply the technique to chaotic signals. We will also provide an example to demonstrate that the methodology can be useful for addressing some fundamental problems in chaotic dynamics.
Lebesgue Ergodic Rational Maps in Parameter Space
Authors: Hawkins Jane
Published: July 2003

We study a family of quadratic rational maps and discuss dynamical and ergodic theoretic properties associated to various parameters. We prove results about the location of ergodic parameters in parameter space and show computer output illustrating the results. We show that the computer algorithm used to produce Julia sets in this setting is valid for all rational maps.
Existence and Computation of Hyperbolic Trajectories of Aperiodically Time Dependent Vector Fields and Their Approximations
Authors: Ju Ning , Small Des , Wiggins Stephen
Published: July 2003

In this paper we give sufficient conditions for the existence of hyperbolic trajectories in aperiodically time dependent vector fields. These conditions do not require the a priori introduction of hyperbolicity into the dynamics of the vector field or assumptions of "time scale separation". The hyperbolic trajectory is obtained as a solution of an integral equation over an infinite time interval. We give an expression for the error obtained when the solution is approximated over a finite time interval. Finally, we show how the method can be numerically implemented in a specific example.
Transient Chaos in Coupled Oscillators with Shape Deformable Potential
Authors: Yamgoué Serge Bruno , Kofané Timoléon Crépin
Published: July 2003

The dynamics of a perturbed system consisting of a particle embedded in a strongly nonlinear potential V(ϕ; r, η) whose shape can be varied continuously as a function of r in the range -1 < r < 1, and coupled to an harmonic oscillator is analyzed. The perturbations are made of the coupling and damping forces. When they are removed, the subsystem formed by the anharmonic oscillator contains saddle points connected by homoclinic loops. Thus, the whole unperturbed system has saddle-centre points whose stable and unstable manifolds coincide in three-dimensional manifold. We concentrate our analysis of the perturbed system in the regions near these saddle-centre points. First, the Melnikov theory is used to investigate the presence of horseshoes chaos in the dynamics. Due to some discrepancies of the Melnikov theory, we next rederive the boundary between the regions of regular and irregular motions in the parameters space by using regular perturbation expansion. It is found here that for small values of the natural pulsation ω of the linear oscillator, complicated behavior intensifies in the system as the absolute value of the shape parameter r approaches zero. On the contrary, chaotic motion intensifies according as r decreases from values close to 1 to values close to -1, for large ω. The numerical analysis, which includes computation of maximal Lyapunov exponent, bifurcation diagrams and Poincaré sections, shows that the system exhibits transient stochastic behavior, but ultimately settles down on a simple set which is either a fixed point or a limit cycle. The dependence of this transient behavior on the system parameters agrees qualitatively well with the analytical predictions.
Experiments on Direct Chaotic Communications in Microwave Band
Authors: Dmitriev Alexander S. , Kyarginsky Boris Ye. , Panas Andrey I. , Starkov Sergey O.
Published: July 2003

We discuss a concept of Direct Chaotic Communications (DCC) that is based on the following ideas: (1) chaotic oscillator generates signals directly in a specified microwave band; (2) information component is put in the chaotic signal by means of formation of an appropriate stream of chaotic radio pulses; (3) envelope detection is used. The principle of communications is confirmed experimentally in microwave band. Transmission rates up to 100 Mbps are demonstrated.
A Comparative Study on Realization of Chua's Circuit: Hybrid Realizations of Chua's Circuit Combining the Circuit Topologies Proposed for Chua's Diode and Inductor Elements
Authors: Kiliç Recai
Published: July 2003

Several realizations of Chua's circuit have been proposed in the literature. The methodologies used in these realizations can be divided into two basic categories. In the first approach, a variety of circuit topologies have been considered for realizing the nonlinear resistor, NR in Chua's circuit. The main idea in the second approach related to the implementation of the circuit is an inductorless realization of Chua's circuit. For this purpose, several circuit topologies serving as a synthetic inductor, i.e. inductance simulator, are used instead of the inductor element in Chua's circuit. In this study, after comparing the circuit topologies proposed for Chua's diode and the inductor element in the circuit, we will present six alternative hybrid realizations of Chua's circuit combining circuit topologies proposed for the nonlinear resistor and the inductor element in the literature. The PSpice simulation experiments confirm that the six alternative hybrid realizations of the circuit exhibit the original chaotic behavior of Chua's circuit.
A Nonlocal Eigenvalue Problem and the Stability of Spikes for Reaction–Diffusion Systems with Fractional Reaction Rates
Authors: Wei Juncheng , Winter Matthias
Published: July 2003

We consider a nonlocal eigenvalue problem which arises in the study of stability of spike solutions for reaction–diffusion systems with fractional reaction rates such as the Sel'kov model, the Gray–Scott system, the hypercycle of Eigen and Schuster, angiogenesis, and the generalized Gierer–Meinhardt system. We give some sufficient and explicit conditions for stability by studying the corresponding nonlocal eigenvalue problem in a new range of parameters.
Hopf Bifurcations of Bi-Parameter Ordinary Differential Systems
Authors: Zhang R. , Wei J. , Huang Q.
Published: July 2003

This paper considers Hopf bifurcations of the ordinary differential systems with two parameters. The results obtained here are substantial generalizations of the well-known Hopf Bifurcation Theorem, from the case of a single parameter to the case of multiple parameters.
Constructive Chemical Processors — Experimental Evidence that Shows this Class of Programmable Pattern Forming Reactions Exist at the Edge of a Highly Nonlinear Region
Authors: de Lacy Costello B. P. J.
Published: July 2003

An adapted chemical processor for the computation of a mixed cell Voronoi diagram has been fabricated. A novel copper ferrocyanide based system was combined with a ferric ferrocyanide based system. At higher substrate loading the predictable (programmable) pattern forming structure is lost as the copper system is subject to a chemical instability. The unstable copper system and analogous systems constitute a new class of pattern forming reactions.
A Note on Hopf Bifurcation in Chen's System
Authors: Li Changpin , Chen Guanrong
Published: July 2003

In this technical note, the Hopf bifurcation in Chen's system is studied. Some corresponding dynamics are also discussed briefly.
Isochronous Foci for Analytic Differential Systems
Authors: Giné Jaume
Published: July 2003

Consider the two-dimensional autonomous systems of differential equations of the form [Formula: see text] where P(x, y) and Q(x, y) are analytic functions. The origin is a strong focus of this system if λ ≠ 0 and is either a weak focus or its center if λ = 0. In this work we provide some sufficient conditions to have an isochronous focus at the origin.
Exact Compact-Like Traveling Kinks and Pulses: Another Way for High Flow Communications
Authors: Comte J. C.
Published: July 2003

We show that by suitably choosing the analytical form of a solitary wave solution of discrete ϕ4 models, it is possible to calculate the potential parameters which allow the propagation of compact (kink and pulses) solutions. Our numerical simulations show that narrow kinks and pulses with finite extent can propagate freely. Moveover, our numerical simulations reveal that the two successive pulses at a relative distance of two lattice spacings propagate freely, i.e. without interaction, which presents considerable interest in the data transmission field. Finally an experimental electronic device holding the propagation of such entities is proposed.
Modding Out a Continuous Rotation Symmetry for Disentangling a Laser Dynamics
Authors: Letellier Christophe
Published: July 2003

When a laser system is studied, the time evolution of the light intensity emitted by the laser cavity is recorded. The phase portrait reconstructed from that time series never presents symmetry although the amplitude equations always generate phase portraits with symmetry properties. It is shown that the detuning between the normalized steady-state laser frequency and the molecular resonance frequency induces a continuous rotation symmetry. This equivariant dynamics is linked with the dynamics underlying the experimental observations of the light intensity through a system for which the symmetry properties are modded out.
The Impact of Noise and Sampling Frequency on the Control of Peak-to-Peak Dynamics
Authors: Piccardi Carlo , Rinaldi Sergio
Published: July 2003

A chaotic system with a nearly two-dimensional attractor can be modeled by means of its Peak-to-Peak Dynamics (PPD). Such a compact modeling, which is only based on the availability of output time series, is the starting point for designing effective controllers. In previous papers, it has been shown that the method works very well in an ideal situation, namely when the system is not affected by noise and the output can be continuously measured. In this paper, we consider a realistic environment, where the system is affected by process and measurement noise and the output is sampled at a predefined frequency. It will be shown that, in most cases, simple filtering and peak-detection techniques allow one to reconstruct the PPD, and thus to derive effective controllers. This proves that chaos control based on PPD is sufficiently robust with respect to noise and sampling.
On Optimal Detection of Noncoherent Chaos-Shift-Keying Signals in a Noisy Environment
Authors: Lau Francis C. M. , Tse Chi K.
Published: July 2003

Recently, an optimal noncoherent detection technique for chaos-shift-keying digital communication system has been proposed. It has been stated that computational intensity showed increases that were exponential with the spreading factor. In this Letter, we show that the implementation of the optimal detector can be made independent of the chaotic maps used, and that the computational intensity will increase almost linearly with the spreading factor. In particular, we use a tent map as an example to illustrate the decoding algorithm. The bit error performance of the system is then evaluated by computer simulations for a range of spreading factors. Further, we extend the optimal decoding algorithm for maps of higher dimension. The bit error performance for the case of simple 2-D maps are compared with that obtained using the tent map. Finally, the effect of increasing spreading factor on the bit error performance is studied for the case of 2-D maps.
Calcium Dynamics and Generation of Propagating Waves in a Coupled Ensemble of Neurons with Random Connection Strengths
Authors: Bondarenko Vladimir E. , Chay Teresa Ree
Published: July 2003

Recent experimental investigations of the brain show that excitatory α-amino-3-hydroxy-5-methyl-4-isoxazdepropionic acid (AMPA) secreting neurons, inhibitory γ-aminobutyric acid (GABA) secreting neurons, and intracellular calcium play important roles in neural network activities. Specifically, they influence the synchronization and desynchronization of neural ensembles, calcium dynamics in neurons, the generation of waves which propagate along the network. To simulate these types of activities a neural network model is developed which takes into account AMPA and GABA synapses, intracellular calcium, and calcium stores. It is found that the neural network model produces different types of activities, synchronization and desynchronization of neural cells, and propagating waves which are observed in the experiments. The type of activity depends on the type of synapses, connection strengths, values of injected current, and calcium release rate from intracellular calcium store. A mechanism of propagating wave generation based on the reduced connectivity between neurons is proposed.
Decoding Digital Information from the Cascaded Heterogeneous Chaotic Systems
Authors: Tao Chao , Du Gonghuan , Zhang Yu
Published: July 2003

In this paper, we propose a new approach to breaking down chaotic communication scheme by attacking its encryption keys. A remarkable advancement is that it can decode the hidden message exactly. This makes it become possible to break down some cascaded chaotic communication systems. We also decode digital information from the cascaded heterogeneous chaotic communication system and give the simulation results.
COLONY OF THE FUNGUS Aspergillus oryzae AND SELF-AFFINE FRACTAL GEOMETRY OF GROWTH FRONTS
Authors: MATSUURA SHU , MIYAZIMA SASUKE
Published: July 2003

A variety of colony shapes of the fungus Aspergillus oryzae under varying environmental conditions such as the nutrient concentration, medium stiffness and incubation temperature are obtained, ranging from a homogeneous Eden-like to a ramified DLA-like pattern. The roughness σ(l, h) of the growth front of the band-shaped colony, where h is the mean front height within l of the horizontal range, satisfies the self-affine fractal relation under favorable environmental conditions. In the most favorable condition of our experiments, its characteristic exponent is found to be a little larger than that of the 2-dimensional Eden model.
SELF-AFFINE RUPTURE LINES IN PAPER SHEETS
Authors: KERTÉSZ JÁNOS , HORVÁTH VIKTOR K. , WEBER FERENC
Published: July 2003

Experiments were carried out using a tensile testing machine to study the morphology of rupture lines in paper. Constant velocity strain was applied until the breaking process separated the sample into two pieces. The resulting quasi one-dimensional patterns show scaling correlations usually over two orders of magnitudes. The measured values of the Hurst exponent ζ are in the range 0.63 < ζ < 0.72. The relevance of models of statistical physics in the interpretation of the results is discussed.
A series‐type multistage production system with random demand
Authors: Chen Ying-Chieh
Published: July 2003

We propose a mathematical model which considers the
series‐type product structure with n − 1 predecessors. Our objective is to obtain the optimal production functions, in the planning horizon [0, T], based on the assumptions (1) that the cost of production unit is a linear function of production quantity in a time unit, (2) that sales of finished goods occur at the end of planning horizon, and (3) that product demand is a random variable. Then the phenomenon of optimal solution is discussed.
On common fixed points of pairs of a single and a multivaluedcoincidentally commuting mappings in D‐metric spaces
Authors: Dhage B. C. , Asha A. Jennifer , Kang S. M.
Published: July 2003

The present paper studies some common fixed‐point theorems for
pairs of a single‐valued and a multivalued coincidentally commuting mappings in D‐metric spaces satisfying a certain generalized contraction condition. Our result generalizes more than a dozen known fixed‐point theorems in D‐metric spaces including those of Dhage (2000) and Rhoades (1996).
Platelet Activation Induces Cell-Surface Immunoreactive Tissue Factor Expression, Which Is Modulated Differently by Antiplatelet Drugs
Authors: Camera Marina , Frigerio Marta , Toschi Vincenzo , Brambilla Marta , Rossi Francesca , Cottell David C. , Maderna Paola , Parolari Alessandro , Bonzi Roberto , De Vincenti Ombretta , Tremoli Elena
Published: July 2003

Objective—

Tissue factor (TF) is the main activator of the coagulation cascade occurring in physiologic and pathologic conditions. Recent data suggest that human platelets might contain TF that is possibly derived from leukocytes. In this study, we investigated whether intraplatelet TF can be exposed on the membrane by platelet agonists. The modulation of this process by antiplatelet drugs has been evaluated as well.

Methods and Results—

Flow cytometric analysis of unstimulated platelets showed a small amount of membrane-associated immunoreactive TF (irTF) in whole blood, platelet-rich plasma, and washed platelets isolated from healthy subjects. ADP, thrombin receptor-activating peptide, and epinephrine significantly increased functionally active, membrane-associated irTF. ADP induced irTF exposure in a concentration- and time-dependent fashion. Agonist-induced irTF expression was completely inhibited by iloprost but not by aspirin. Interestingly, glycoprotein IIb/IIIa antagonists did not inhibit but rather potentiated the stimulatory effect of ADP on platelet irTF expression. Real-time polymerase chain reaction experiments showed detectable amounts of TF mRNA in unstimulated platelets.

Conclusions—

These findings indicate that platelet agonists and antiplatelet drugs might modulate platelet-associated irTF expression. Regulated TF expression establishes the potential for a previously unrecognized role for platelets in sustaining thrombus formation and growth via coagulation-mediated mechanisms.
Endothelial Cell Glycocalyx Modulates Immobilization of Leukocytes at the Endothelial Surface
Authors: Constantinescu Alina A. , Vink Hans , Spaan Jos A.E.
Published: July 2003

Objective—

A thick endothelial glycocalyx provides the endothelial surface with a nonadherent shield. Oxidized LDL (Ox-LDL) degrades the endothelial glycocalyx. We hypothesized that glycocalyx degradation stimulates leukocyte-endothelial cell adhesion, whereas intravascular supplementation with sulfated polysaccharides reconstitutes the endothelial glycocalyx and attenuates Ox-LDL-induced leukocyte-endothelial cell adhesion.

Methods and Results—

Degradation of the endothelial glycocalyx by local microinjection of heparitinase (10 to 50 U/mL) into mouse cremaster venules dose-dependently increased the number of adherent leukocytes. Systemic administration of Ox-LDL (0.4 mg/100 g body weight) induced 10.1±0.9 adherent leukocytes/100 μm at 60 minutes. In the venules perfused with 500-kDa dextran sulfate (1 mg/mL), the number of adherent leukocytes at 60 minutes after Ox-LDL bolus application was not influenced (9.2±1.0 leukocytes/100 μm). However, the venules locally perfused with heparan sulfate (10 mg/mL) or heparin (1 mg/mL) displayed a significantly lower number of adherent leukocytes induced by Ox-LDL: 5.1±0.7 and 5.4±0.9 leukocytes/100 μm, respectively (
P
<0.05). Fluorescently labeled heparan sulfate and heparin, but not dextran sulfate, attached to the venule luminal surface after Ox-LDL administration.

Conclusions—

Endothelial glycocalyx degradation stimulates leukocyte immobilization at the endothelial surface. Circulating heparan sulfate and heparin attach to the venule wall and attenuate Ox-LDL-induced leukocyte immobilization.
Aortic Dissection Precedes Formation of Aneurysms and Atherosclerosis in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice
Authors: Saraff Kiran , Babamusta Fjoralba , Cassis Lisa A. , Daugherty Alan
Published: July 2003

Objective—

We sought to define the temporal characteristics of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and to provide mechanistic insight into the development of this vascular pathology in apolipoprotein E-deficient (apoE-/-) mice.

Methods and Results—

Male apoE-/- mice were infused with AngII for 1 to 56 days. Suprarenal arteries were sequentially sectioned, and cellular features were defined by histologic and immunocytochemical techniques. The initial identified event was medial accumulation of macrophages in regions of elastin degradation. Subsequent medial dissection was associated with luminal dilation and thrombus formation. Thrombi were usually constrained by adventitial tissue, although ≈10% of mice died due to rupture. Thrombi led to profound inflammation that was characterized by infiltration of macrophages and T and B lymphocytes. Remodeling of the tissues was associated with regeneration of elastin fibers and reendothelialization of the dilated luminal surface. Aneurysmal tissue underwent profound neovascularization. Atherosclerotic lesions were only detected after development of the aneurysms.

Conclusions—

The initial event in AngII-induced AAA is a focal dissection in the suprarenal region. The progression of AAA precedes the development of overt atherosclerotic lesions.
Administration of Tyrosyl Radical–Oxidized HDL Inhibits the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Macdonald Dawn L. , Terry Timothy L. , Agellon Luis B. , Nation Patrick N. , Francis Gordon A.
Published: July 2003

Objective—

Tyrosyl radical–oxidized HDL (tyrHDL) increases the ability of cells to donate cholesterol to apolipoprotein (apo) A-I for HDL particle formation. We tested whether treatment with tyrHDL raises endogenous HDL cholesterol levels and decreases atherosclerosis development in apoE-deficient mice.

Methods and Results—

Tyrosyl radical oxidation of mouse HDL induced formation of apoAI-AII heterodimers and enhanced the ability of mouse HDL to deplete cultured fibroblasts of their regulatory pool of cholesterol.
125
I-labeled HDL and tyrHDL delivered intraperitoneally were cleared at similar rates from plasma of chow-fed apoE-deficient mice. ApoE-deficient mice injected intraperitoneally twice weekly with 150 μg tyrHDL from age 10 to 18 weeks showed a maximum 2.3-fold increase in endogenous HDL cholesterol levels, which fell toward the end of the treatment period. tyrHDL treatment resulted in 37% less aortic lesion development than in control HDL-treated mice (
P
<0.001) and 67% less than in saline-injected animals (
P
<0.001).

Conclusions—

Administration of tyrHDL for 8 weeks resulted in significantly less atherosclerosis development in apoE-deficient mice than injection of HDL or saline. Molecules increasing mobilization of cellular cholesterol to apoAI for HDL particle formation would be expected to decrease atherosclerosis without necessarily causing sustained increases in circulating HDL cholesterol levels.
Increased Atherosclerotic Lesions in ApoE Mice With Plasma Phospholipid Transfer Protein Overexpression
Authors: Yang Xiao Ping , Yan Daoguang , Qiao Chunping , Liu Rui Jie , Chen Jer-Gin , Li Juan , Schneider Martina , Lagrost Laurent , Xiao Xiao , Jiang Xian-Cheng
Published: July 2003

Objective—

Plasma phospholipid transfer protein (PLTP) is involved in the metabolism of HDL and apolipoprotein B (apoB)-containing lipoproteins. Atherosclerosis susceptibility is decreased in mice with PLTP deficiency that is associated with decreased liver production of apoB-containing lipoproteins and increase in their antioxidant. To investigate additionally the effect of PLTP on the development of atherosclerosis, we overexpressed PLTP in mice.

Methods and Results—

PLTP was overexpressed in apoE knockout mice using an adenovirus-associated virus (AAV)-mediated system. Plasma PLTP activity was 1.3- to 2-fold higher in mice injected with AAV-PLTP than in mice injected with control AAV-GFP, and PLTP levels were sustained during the experiment period (4 months). We show that 2-fold increased PLTP activity results in (1) a decrease in HDL cholesterol, HDL phospholipid, and apoAI levels; (2) a decrease in vitamin E contents in total plasma and in individual lipoprotein fractions; (3) an increase in lipoprotein oxidizability as assessed by copper-induced formation of conjugated dienes; (4) an increase in autoantibodies against oxidized apoB-containing particles; and (5) an increase in atherosclerosis lesions in proximal aorta.

Conclusions—

These observations indicate that elevated plasma PLTP levels constitute a novel, long-term risk factor for atherosclerosis.
17β-Estradiol Attenuates Development of Angiotensin II–Induced Aortic Abdominal Aneurysm in Apolipoprotein E–Deficient Mice
Authors: Martin-McNulty Baby , Tham Doris M. , da Cunha Valdeci , Ho Jerrick J. , Wilson Dennis W. , Rutledge John C. , Deng Gary G. , Vergona Ronald , Sullivan Mark E. , Wang Yi-Xin
Published: July 2003

Objectives—

Angiotensin II (Ang II) promotes vascular inflammation, accelerates atherosclerosis, and induces abdominal aortic aneurysm (AAA). These changes were associated with activation of nuclear factor (NF)-κB–mediated induction of proinflammatory genes. The incidence of AAA in this model was higher in male than in female mice, and the vascular effects of estrogen may be associated with anti-inflammatory actions. The present study was undertaken to test the hypothesis that estrogen can attenuate Ang II–induced AAA in apolipoprotein E–deficient mice via its anti-inflammatory mechanism.

Methods and Results—

Infusion of Ang II (1.44 mg/kg per d for 1 month) induced AAA in 90% of the animals (n=20) with an expansion of the suprarenal aorta (diameter 1.9±0.14 mm versus <1 mm in normal mice). In mice treated with 17β-estradiol (E2, 0.25-mg subcutaneous pellets), Ang II induced AAA only in 42% of the animals (n=19) with a significant reduction of average diameters of the suprarenal aorta (1.5±0.14 mm). E2 also decreased the expressions of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, E-selectin, monocyte chemotactic protein-1, and macrophage-colony stimulating factor in the aorta.

Conclusions—

These data suggest that attenuation of AAA by E2 is associated with inhibition of proinflammatory gene expression.
Variability of Phase Shift Between Blood Pressure and Heart Rate Fluctuations
Authors: Halámek Josef , Kára Tomáš , Jurák Pavel , Souček Miroslav , Francis Darrel P. , Davies L. Ceri , Shen Win K. , Coats Andrew J.S. , Novák Miroslav , Nováková Zuzana , Panovský Roman , Toman Jiří , Šumbera Josef , Somers Virend K.
Published: July 2003

Background—

We postulated that the variability of the phase shift between blood pressure and heart rate fluctuation near the frequency of 0.10 Hz might be useful in assessing autonomic circulatory control.

Methods and Results—

We tested this hypothesis in 4 groups of subjects: 28 young, healthy individuals; 13 elderly healthy individuals; 25 patients with coronary heart disease; and 19 patients with a planned or implanted cardioverter-defibrillator (ICD recipients). Data from 5 minutes of free breathing and at 2 different, controlled breathing frequencies (0.10 and 0.33 Hz) were used. Clear differences (
P
<0.001) in variability of phase were evident between the ICD recipients and all other groups. Furthermore, at a breathing frequency of 0.10 Hz, differences in baroreflex sensitivity (
P
<0.01) also became evident, even though these differences were not apparent at the 0.33-Hz breathing frequency.

Conclusions—

The frequency of 0.10 Hz represents a useful and potentially important one for controlled breathing, at which differences in blood pressure–RR interactions become evident. These interactions, whether computed as a variability of phase to define stability of the blood pressure–heart rate interaction or defined as the baroreflex sensitivity to define the gain in heart rate response to blood pressure changes, are significantly different in patients at risk for sudden arrhythmic death. In young versus older healthy individuals, only baroreflex gain is different, with the variability of phase being similar in both groups. These measurements of short-term circulatory control might help in risk stratification for sudden cardiac death.
Postnatal Recapitulation of Embryonic Hedgehog Pathway in Response to Skeletal Muscle Ischemia
Authors: Pola Roberto , Ling Leona E. , Aprahamian Tamar R. , Barban Elena , Bosch-Marce Marta , Curry Cynthia , Corbley Michael , Kearney Marianne , Isner Jeffrey M. , Losordo Douglas W.
Published: July 2003

Background—

Hedgehog (Hh) proteins are morphogens regulating epithelial–mesenchymal signaling during several crucial processes of embryonic development, including muscle patterning. Sonic (Shh), Indian (Ihh), and Desert (Dhh) hedgehog constitute the repertoire of Hh genes in humans. The activities of all 3 are transduced via the Patched (Ptc1) receptor. Recent observations indicate that exogenous administration of Shh induces angiogenesis. Here, we studied whether the endogenous Hh pathway, in addition to its functions during embryogenesis, plays a physiological role in muscle regeneration after ischemia in adults.

Methods and Results—

We found that skeletal muscle ischemia induces strong local upregulation of Shh mRNA and protein. In addition, the Ptc1 receptor is activated in interstitial mesenchymal cells within the ischemic area, indicating that these cells respond to Shh and that the Shh pathway is functional. We also found that Shh-responding cells produce vascular endothelial growth factor under ischemic conditions and that systemic treatment with a Shh-blocking antibody inhibits the local angiogenic response and the upregulation of vascular endothelial growth factor.

Conclusions—

Our study shows that the Hh signaling may be recapitulated postnatally in adult and fully differentiated muscular tissues and has a regulatory role on angiogenesis during muscle regeneration after ischemia. These findings demonstrate a novel biological activity for the Hh pathway with both fundamental and potential therapeutic implications.
Paradoxical Upregulation of Tumor Suppressor Protein p53 in Serum-Stimulated Vascular Smooth Muscle Cells
Authors: Mnjoyan Zakar H. , Dutta Ranjan , Zhang Di , Teng Ba-Bie , Fujise Ken
Published: July 2003

Background—

The proliferative response of vascular smooth muscle cells (VSMCs) to various growth stimuli is critical for atherosclerosis and postangioplasty restenosis. Although tumor suppressor protein p53 plays a critical role in the elimination of cancerous cells, recent genetic studies have indicated that it also protects against atherosclerosis and restenosis.

Methods and Results—

We examined the levels of p53 protein in normal VSMCs before and after serum stimulation. The p53 protein levels increased robustly on stimulation. Upregulated p53 protein was capable of binding to the p53 consensus sequence, as shown by electrophoretic mobility shift assay. In addition, p53 upregulation was associated with increases in the transcript and protein levels of p21
WAF1/CIP1
and Bax, as shown by real-time reverse transcriptase–polymerase chain reaction and Western blot analysis, respectively. Furthermore, the upregulation of p21
WAF1/CIP1
and Bax was followed by cell-cycle arrest and apoptosis induction, as shown by 5-bromo-2′-dUTP incorporation assay and terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling staining, respectively. Finally, double-staining analyses showed that the majority of p53-expressing cells also expressed p21
WAF1/CIP1
and Bax proteins.

Conclusions—

p53 protein expression in quiescent VSMCs is paradoxically increased by application of a growth stimulus. Through the mediation of p21
WAF1/CIP1
and Bax, the induced p53 protein negatively regulates the growth of dividing VSMCs, thereby minimizing the inappropriate accumulation of VSMCs. Therefore, p53 may be a negative regulator of VSMC growth.
Diabetes-Induced Oxidative Stress and Low-Grade Inflammation in Porcine Coronary Arteries
Authors: Zhang LiFeng , Zalewski Andrew , Liu Yuchuan , Mazurek Tomasz , Cowan Scott , Martin Jack L. , Hofmann Susanna M. , Vlassara Helen , Shi Yi
Published: July 2003

Background—

Multiple pathways contribute to accelerated coronary atherosclerosis in diabetics, including increased oxidative stress and inflammatory burden. Accordingly, the mechanisms of abnormal formation of reactive oxygen species and the changes in inflammatory gene expression were examined in diabetic coronary arteries.

Methods and Results—

In pigs with streptozotocin-induced diabetes, superoxide formation was augmented in coronary media and adventitia because of increased NAD(P)H oxidase activity (3 months) accompanied by upregulated expression of its cytosolic subunit, p22
phox
. Diabetes-induced oxidative stress resulted in the inflammatory response in the adventitia (increased expression of interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, vascular cell adhesion molecule-1 [VCAM-1]) and in the media (VCAM-1). To examine the mechanisms of these changes, studies with isolated coronary fibroblasts were undertaken. Advanced glycation end products (AGEs), rather than glucose itself, upregulated expression of interleukin-6, VCAM-1, and monocyte chemotactic protein-1 mRNAs. These results were paralleled by increased interleukin-6 secretion (
P
<0.01) and augmented leukocyte adhesion to AGE-stimulated coronary cells (
P
<0.001). AGEs increased expression of phosphorylated forms of mitogen-activated protein kinases in coronary cells (ERK1/2 and JNK) and resulted in redox-sensitive expression of inflammatory genes that was inhibited by several inhibitors of oxidative pathways [NAD(P)H oxidase inhibitors,
N
-acetylcysteine, and pyrrolidine dithiocarbamate].

Conclusions—

Diabetes increased NAD(P)H oxidase activity and oxidative stress, producing inflammatory responses in porcine coronary media and adventitia. AGEs activated ERK1/2 and JNK signaling pathways and induced the expression of several inflammatory genes in coronary cells in a redox-sensitive manner. These results suggest the involvement of AGEs in the development of accelerated coronary atherosclerosis in diabetes.
Influence of Anterior Mitral Leaflet Second-Order Chordae Tendineae on Left Ventricular Systolic Function
Authors: Nielsen Sten Lyager , Timek Tomasz A. , Green G. Randall , Dagum Paul , Daughters George T. , Hasenkam J. Michael , Bolger Ann F. , Ingels Neil B. , Miller D. Craig
Published: July 2003

Background—

The contribution of anterior mitral leaflet second-order (“strut”) chordae tendineae to left ventricular (LV) systolic mechanics is debated; we measured the in vivo contribution of anterior chordae tendineae (ACT) and posterior chordae tendineae (PCT) to regional and global LV contractile function.

Methods and Results—

Eight sheep had radiopaque markers implanted in the LV epicardium, partitioning the ventricle into 12 regions. Microminiature force transducers and snares were sutured to anterior leaflet “strut” chordae originating from ACT and PCT papillary muscles. Chordal tension, marker images, and hemodynamic data were acquired before and after (CUT) severing ACT and PCT. Fractional area shrinkage and slope of the regional end-diastolic area–regional stroke work relation (r-PRSW) were computed for each LV region. CUT did not affect global LV systolic function but reduced FAS in LV segments near the PCT insertion site: equatorial posterior lateral (19±2% versus 16±2%,
P
<0.05), apical posterior lateral (23±4% versus 19±4%,
P
<0.05), and posterior medial LV segments (16±2% versus 13±2%,
P
<0.05). r-PRSW fell near both the ACT (equatorial anterior medial [84±8 versus 62±11 mm Hg,
P
<0.05] and lateral [73±7 versus 53±9 mm Hg,
P
<0.05]) and PCT (apical posterior medial [91±12 versus 67±17 mm Hg,
P
<0.05] and lateral [72±8 versus 59±9 mm Hg,
P
<0.05]) LV insertion sites. Maximum tension in PCT was higher than in ACT (0.81±0.1 versus 0.52±0.08
N
,
P
<0.01).

Conclusions—

Dividing anterior leaflet strut chordae in sheep was associated acutely with regional LV systolic dysfunction near the chordal insertion sites. Caution is necessary when embarking on procedures that cut second-order chordae to treat ischemic mitral regurgitation, since this may compromise LV systolic function in ventricles that are already impaired.
Effect of Endothelial Shear Stress on the Progression of Coronary Artery Disease, Vascular Remodeling, and In-Stent Restenosis in Humans
Authors: Stone Peter H. , Coskun Ahmet U. , Kinlay Scott , Clark Maureen E. , Sonka Milan , Wahle Andreas , Ilegbusi Olusegun J. , Yeghiazarians Yerem , Popma Jeffrey J. , Orav John , Kuntz Richard E. , Feldman Charles L.
Published: July 2003

Background—

Native atherosclerosis and in-stent restenosis are focal and evolve independently. The endothelium controls local arterial responses by transduction of shear stress. Characterization of endothelial shear stress (ESS) may allow for prediction of progression of atherosclerosis and in-stent restenosis.

Methods and Results—

By using intracoronary ultrasound, biplane coronary angiography, and measurement of coronary blood flow, we represented the artery in accurate 3D space and determined detailed characteristics of ESS and arterial wall/plaque morphology. Patients who underwent stent implantation and who had another artery with luminal obstruction <50% underwent intravascular profiling initially and after 6-month follow-up. Twelve arteries in 8 patients were studied: 6 native and 6 stented arteries. In native arteries, regions of abnormally low baseline ESS exhibited a significant increase in plaque thickness and enlargement of the outer vessel wall, such that lumen radius remained unchanged (outward remodeling). Regions of physiological ESS showed little change. Regions with increased ESS exhibited outward remodeling with normalization of ESS. In stented arteries, there was an increase in intima-medial thickness, a decrease in lumen radius, and an increase in ESS at all levels of baseline ESS.

Conclusions—

The present study represents the first experience in humans relating ESS to subsequent outcomes in native and stented arteries. Regions of low ESS develop progressive atherosclerosis and outward remodeling, areas of physiological ESS remain quiescent, and areas of increased ESS exhibit outward remodeling. ESS may have a limited role in in-stent restenosis. This technology can predict areas of minor plaque likely to exhibit progression of atherosclerosis.