bluuebunny/crossref_metadata_2025 huggingface dataset:
HNN Extensions of Inverse Semigroups and Applications
Authors: Yamamura Akihiro
Published: October 2003

Originally the concept of an HNN extension of a group was introduced by Higman, Neumann and Neumann in their study of embeddability of groups. Howie introduced the concept of HNN extensions of semigroups and showed embeddability in the case that the associated subsemigroups are unitary. On the other hand, T. E. Hall showed the embeddability of HNN extensions of inverse semigroups of a special type in his survey article on amalgamation of inverse semigroups. We introduce a more general definition of an HNN extension and show that free inverse semigroups and the bicyclic semigroup are HNN extensions of semilattices as examples of our new construction. We discuss weak HNN embeddability in several classes of semigroups and strong HNN embeddability in the class of inverse semigroups. One of our main purposes in the study of HNN extensions of inverse semigroups is to employ HNN extensions to examine some algorithmic problems. We prove the undecidability of Markov properties of finitely presented inverse semigroups using HNN extensions. This result was announced by Vazhenin in 1978, but no proof of it has been published to date. We also show undecidability of several non-Markov properties and discuss some undecidable problems on finitely generated inverse subsemigroups of finitely presented inverse semigroups.
On the Word Problem for Single Relation Monoids with an Unbordered Relator
Authors: Watier Guillaume
Published: October 2003

Let A be an alphabet and u, v two words in A*. We show that the word problem is decidable for the monoid presentation [Formula: see text] if u is unbordered (i.e. non-self-overlapping), u is not a factor of v and |v| ≥ |u|2.
"Fractional Tuning" of the Riccati Equation
Authors: Metzler R. , Glöckle W. G. , Nonnenmacher T. F. , West B. J.
Published: October 2003

The dynamics of a free-falling body in complex materials such as a polymer fluid is phenomenologically modeled using a fractional generalization of the Riccati equation. The solution exhibits a rich behavior in its parametric dependence, and unlike normal free–fall there is no terminal velocity, instead a power–law increase in time is obtained. Within this approach the fractional order allows to tune the resulting equation.
Fractal Trees with Side Branching
Authors: Newman W. I. , Turcotte D. L. , Gabrielov A. M.
Published: October 2003

This paper considers fractal trees with self-similar side branching. The Tokunaga classification system for side branching is introduced, along with the Tokunaga self-similarity condition. Area filling (D = 2) and volume filling (D = 3) deterministic fractal tree constructions are introduced both with and without side branching. Applications to diffusion limited aggregation (DLA), actual drainage networks, as well as biology are considered. It is suggested that the Tokunaga taxonomy may have wide applicability in nature.
The Study on Bivariate Fractal Interpolation Functions and Creation of Fractal Interpolated Surfaces
Authors: Xie Heping , Sun Hongquan
Published: October 2003

In this paper, the methods of construction of a fractal surface are introduced, the principle of bivariate fractal interpolation functions is discussed. The theorem of the uniqueness of an iterated function system of bivariate fractal interpolation functions is proved. Moreover, the theorem of fractal dimension of fractal interpolated surface is derived. Based on these theorems, the fractal interpolated surfaces are created by using practical data.
Fractal Characterization of Irregularly Shaped Images by Frequency Analysis
Authors: Wu Hai-Shan , Gil Joan , Einstein Andrew J.
Published: October 2003

An iterative spectral method is presented for fractal characterization of irregularly shaped (i.e., nonrectangular) images such as microscopic images of cells. The algorithm extends the application of fractal characterization by frequency analysis to images with irregular supports by utilizing information in both the spatial and frequency domains. Experiments with synthetic fractal images demonstrate the efficacy of the proposed method.
Fuzzy Encoding and Decoding: A Study in Information Granularity
Authors: Bortolan Giovanni , Pedrycz Witold
Published: October 2003

The paper elaborates on the encoding and decoding of numerical and nonnumerical data. Proposed are general criteria leading to the distortion-free interfacing mechanisms that help transform information between the systems (or modelling environments) operating at different levels of information granularity. Distinguished are three basic categories of information: numerical, interval-valued, and linguistic (fuzzy). As all of them are dealt with here, the paper subsumes the current studies concentrated exclusively on representing fuzzy sets through their numerical representatives (prototypes). The algorithmic framework in which the distortion-free interfacing is completed is realized through neural networks. Each category of information is treated separately and gives rise to its own specialized architecture of the neural network. Similarly, these networks require carefully designed training sets that fully capture the specificity of the reconstruction problem. Several carefully selected numerical examples are aimed at the illustration of the key ideas.
Inducing a Membership Function of a Category in a Fuzzy-Set-Based Attribute Space
Authors: Liu Weijie , Sugeno Michio
Published: October 2003

Learning from examples has been studied widely. A new approach is presented by Narazaki and Ralescu, where by assigning suitable numerical values to any of the old symbolic attribute values, they give a method to make examples belonging to the same category (concept) concentrated. This paper is an improvement to their study. Instead of a real value from an interval, a vector of fuzzy membership values is used for the assignment in this paper. The vector is obtained based on building a fuzzy set base for each attribute. The new approach presented here involves Narazaki and Ralescu's method as a special case. Its effectiveness is simply explained and verified with three experiments. Results of the experiments show that the new approach is superior to the previous studies.
A Mathematical Setting for Fuzzy Logics
Authors: Gehrke Mai , Walker Carol , Walker Elbert
Published: October 2003

The setup of a mathematical propositional logic is given in algebraic terms, describing exactly when two choices of truth value algebras give the same logic. The propositional logic obtained when the algebra of truth values is the real numbers in the unit interval equipped with minimum, maximum and -x=1-x for conjunction, disjunction and negation, respectively, is the standard propositional fuzzy logic. This is shown to be the same as three-valued logic. The propositional logic obtained when the algebra of truth values is the set {(a, b)|a≤ b and a,b∈[0,1]} of subintervals of the unit interval with component-wise operations, is propositional interval-valued fuzzy logic. This is shown to be the same as the logic given by a certain four element lattice of truth values. Since both of these logics are equivalent to ones given by finite algebras, it follows that there are finite algorithms for determining when two statements are logically equivalent within either of these logics. On this topic, normal forms are discussed for both of these logics.
An Approach for Solving Fuzzy MADM Problems
Authors: Chen Chie-Bein , Wei Chiu-Chi
Published: October 2003

An approach using defuzzifying methods is proposed for the fuzzy multiple attribute decision-making (MADM) problems. The computing effectiveness of the proposed defuzzifying methods combined with the simple additive weighting (SAW) method and the technique for order preference by similarity to ideal solution (TOPSIS) method are evaluated based on a comparison to the improved fuzzy weighted average (IFWA) followed by a ranking method. Both SAW and TOPSIS methods are two of classic MADM methods. The purpose of this application is to make the method easier to program and data easier to manipulate. This results in a more practical method for fuzzy decisions. A numerical example and experiment are discussed to demonstrate the implementation of the methods in different input conditions.
Partition Type Fuzzy Integral Model for Evaluation Process
Authors: Matsushita Yutaka , Kambara Hiroshi
Published: October 2003

This paper formulates "partition type fuzzy integral" which is a fuzzy integral of functions on a partition of the set of all attributes. The identity of it is the set of intermediate fuzzy integrals between the linear form and the usual multilinear fuzzy integrals. In this fuzzy integral, any combination of attributes in the same macro-attribute yields no interactions, but any set of attributes, each member of which belongs to a distinct macro-attribute, causes an interaction. Therefore, we can extract only the essential interactions from the evaluation process by discovering the best expressive partition. An application to a concrete evaluation problem shows the effectiveness of this model.
Coherent Four-Wave Mixing in a Laser-Preproduced Plasma: Optical Frequency Conversion and Two-Dimensional Mapping of Atoms And Ions
Authors: Fedotov A. B. , Koroteev N. I. , Naumov A. N. , Sidorov-Biryukov D. A. , Zheltikov A. M.
Published: October 2003

We discuss applications of coherent four-wave mixing in the plasma of optical breakdown produced by an additional laser pulse (laser-preproduced plasma) for the generation of short-wavelength radiation and the investigation of spatial distribution of atoms and ions. The use of an additional laser for the generation of laser-produced plasma on the surface of a metal target makes it possible to optimize the efficiency of frequency conversion and to implement plasma diagnostics at various stages of plasma expansion. An experimental technique based on hyper-Raman-resonant four-wave mixing is developed for two-dimensional mapping of relative populations of excited atomic and ionic states in laser-produced plasma.
X-Ray Production and Second Harmonic Generation by Superintense Femtosecond Laser Pulses in the Solids with Restricted Thermal Conduction
Authors: Babaev V. G. , Dzhidzhoev M. S. , Gordienko V. M. , Joukov M. A. , Savel'ev A. B. , Timoshenko V. Yu. , Shashkov A. A. , Volkov R. V.
Published: October 2003

Two new types of targets: ultrathin freely suspended carbon films and porous Si, both revealing thermoconductivity restriction leading to plasma overheating upto electron temperature above 1 keV under "moderate" intensities 1015 - 1016 W · cm-2 has been investigated experimentally. For the ultrathin carbon film of 20–30 nm X-ray yield threefold increase has been observed. Computer simulations decribe well the observed behaviour of the X-ray yield, and the electron temperature of 700 eV was deducted for the film of 10 nm in thickness. Por-Si produces greater X-ray flux under intensity of 1016 W · cm-2 as compared to the solid Si. If the intensity increased the total X-ray yield from por-Si undergoes "saturation", while the X-ray yield from solid Si fits as ≈ I2. Simple model to describe the "overheating" of Si plasma using a set of ultrathin films is developed. Some promising advantages of new targets are discussed.
Positional Control of Cell Fate Through Joint Integrin/Receptor Protein Kinase Signaling
Authors: Giancotti Filippo G. , Tarone Guido
Published: October 2003

▪ Abstract  Cells adhere to the extracellular matrix throughout most of their lifetime. This close, intimate contact with the matrix exerts an extraordinary control on the behavior of cells, determining whether they move or stay put, proliferate or remain quiescent, and even live or die. Attachment to the matrix not only enables cells to respond to soluble growth factors and cytokines but also determines the nature of the response. The integrins are a large family of receptors that attach cells to the matrix, organize their cytoskeleton, and cooperate with receptor protein tyrosine kinases to regulate cell fate. Research on integrin signaling is beginning to explain the complex and specific effects that the extracellular matrix exerts on cells.
Ena/VASP Proteins: Regulators of the Actin Cytoskeleton and Cell Migration
Authors: Krause Matthias , Dent Erik W. , Bear James E. , Loureiro Joseph J. , Gertler Frank B.
Published: October 2003

▪ Abstract  Ena/VASP proteins are a conserved family of actin regulatory proteins made up of EVH1, EVH2 domains, and a proline-rich central region. They have been implicated in actin-based processes such as fibroblast migration, axon guidance, and T cell polarization and are important for the actin-based motility of the intracellular pathogen Listeria monocytogenes. Mechanistically, these proteins associate with barbed ends of actin filaments and antagonize filament capping by capping protein (CapZ). In addition, they reduce the density of Arp2/3-dependent actin filament branches and bind Profilin at sites of actin polymerization. Vertebrate Ena/VASP proteins are substrates for PKA/PKG serine/threonine kinases. Phosphorylation by these kinases appears to modulate Ena/VASP function within cells, although the mechanism underlying this regulation remains to be determined.
Proteolysis in Bacterial Regulatory Circuits
Authors: Gottesman Susan
Published: October 2003

▪ Abstract  Proteolysis by cytoplasmic, energy-dependent proteases plays a critical role in many regulatory circuits, keeping basal levels of regulatory proteins low and rapidly removing proteins when they are no longer needed. In bacteria, four families of energy-dependent proteases carry out degradation. In all of them, substrates are first recognized and bound by ATPase domains and then unfolded and translocated to a sequestered proteolytic chamber. Substrate selection depends not on ubiquitin but on intrinsic recognition signals within the proteins and, in some cases, on adaptor or effector proteins that participate in delivering the substrate to the protease. For some, the activity of these adaptors can be regulated, which results in regulated proteolysis. Recognition motifs for proteolysis are frequently found at the N and C termini of substrates. Proteolytic switches appear to be critical for cell cycle development in Caulobacter crescentus, for proper sporulation in Bacillus subtilis, and for the transition in and out of stationary phase in Escherichia coli. In eukaryotes, the same proteases are found in organelles, where they also play important roles.
Transport Protein Trafficking in Polarized Cells
Authors: Muth Theodore R. , Caplan Michael J.
Published: October 2003

▪ Abstract  In order to carry out their physiological functions, ion transport proteins must be targeted to the appropriate domains of cell membranes. Regulation of ion transport activity frequently involves the tightly controlled delivery of intracellular populations of transport proteins to the plasma membrane or the endocytic retrieval of transport proteins from the cell surface. Transport proteins carry signals embedded within their structures that specify their subcellular distributions and endow them with the capacity to participate in regulated membrane trafficking processes. Recently, a great deal has been learned about the biochemical nature of these signals, as well as about the cellular machinery that interprets them and acts upon their messages.
The COP9 Signalosome
Authors: Wei Ning , Deng Xing Wang
Published: October 2003

▪ Abstract  The COP9 signalosome (CSN) is composed of eight distinct subunits and is highly homologous to the lid sub-complex of the 26S proteasome. CSN was initially defined as a repressor of photomorphogenesis in Arabidopsis, and it has now been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Recently, CSN was revealed to have a metalloprotease activity centered in the CSN5/Jab1 subunit, which removes the post-translational modification of a ubiquitin-like protein, Nedd8/Rub1, from the cullin component of SCF ubiquitin E3 ligase (i.e., de-neddylation). In addition, CSN is associated with de-ubiquitination activity and protein kinase activities capable of phosphorylating important signaling regulators. The involvement of CSN in a number of cellular and developmental processes has been attributed to its control over ubiquitin-proteasome-mediated protein degradation.
Flower Development: Initiation, Differentiation, and Diversification
Authors: Zik Moriyah , Irish Vivian F.
Published: October 2003

▪ Abstract  Flowering is one of the most intensively studied processes in plant development. Despite the wide diversity in floral forms, flowers have a simple stereotypical architecture. Flowers develop from florally determined meristems. These small populations of cells proliferate to form the floral organs, including the sterile outer organs, the sepals and petals, and the inner reproductive organs, the stamens and carpels. In the past decade, analyses of key flowering genes have been carried out primarily in Arabidopsis and have provided a foundation for understanding the underlying molecular genetic mechanisms controlling different aspects of floral development. Such studies have illuminated the transcriptional cascades responsible for the regulation of these key genes, as well as how these genes effect their functions. In turn, these studies have resulted in the refinement of the original ideas of how flowers develop and have indicated the gaps in our knowledge that need to be addressed.
Adult Stem Cell Plasticity: Fact or Artifact?
Authors: Raff Martin
Published: October 2003

▪ Abstract  There has been unprecedented recent interest in stem cells, mainly because of the hope they offer for cell therapy. Adult stem cells are an attractive source of cells for therapy, especially in view of the recent claims that they are remarkably plastic in their developmental potential when exposed to new environments. Some of these claims have been either difficult to reproduce or shown to be misinterpretations, leaving the phenomenon of adult stem cell plasticity under a cloud. There are, however, other examples of plasticity where differentiated cells or their precursors can be reprogrammed by extracellular cues to alter their character in ways that could have important implications for cell therapy and other forms of regenerative treatment.
Tetraspanin Proteins Mediate Cellular Penetration, Invasion, and Fusion Events and Define a Novel Type of Membrane Microdomain
Authors: Hemler Martin E.
Published: October 2003

▪ Abstract  This review summarizes key aspects of tetraspanin proteins, with a focus on the functional relevance and structural features of these proteins and how they are organized into a novel type of membrane microdomain. Despite the size of the tetraspanin family and their abundance and wide distribution over many cell types, most have not been studied. However, from studies of prototype tetraspanins, information regarding functions, cell biology, and structural organization has begun to emerge. Genetic evidence points to critical roles for tetraspanins on oocytes during fertilization, in fungi during leaf invasion, in Drosophila embryos during neuromuscular synapse formation, during T and B lymphocyte activation, in brain function, and in retinal degeneration. From structure and mutagenesis studies, we are beginning to understand functional subregions within tetraspanins, as well as the levels of connections among tetraspanins and their many associated proteins. Tetraspanin-enriched microdomains (TEMs) are emerging as entities physically and functionally distinct from lipid rafts. These microdomains now provide a context in which to evaluate tetraspanins in the regulation of growth factor signaling and in the modulation of integrin-mediated post-cell adhesion events. Finally, the enrichment of tetraspanins within secreted vesicles called exosomes, coupled with hints that tetraspanins may regulate vesicle fusion and/or fission, suggests exciting new directions for future research.
Regulation of MAP Kinase Signaling Modules by Scaffold Proteins in Mammals
Authors: Morrison Deborah K. , Davis Roger J.
Published: October 2003

▪ Abstract  The mitogen-activated protein kinase (MAPK) group of serine/threonine protein kinases mediates the response of cells to many extracellular stimuli such as cytokines and growth factors. These protein kinases include the extracellular signal-regulated protein kinases (ERK) and two stress-activated protein kinases (SAPK), the c-Jun N-terminal kinases (JNK), and the p38 MAPK. The enzymes are evolutionarily conserved and are activated by a common mechanism that involves a protein kinase cascade. Scaffold proteins have been proposed to interact with MAPK pathway components to create a functional signaling module and to control the specificity of signal transduction. Here we critically evaluate the evidence that supports a physiologically relevant role of MAPK scaffold proteins in mammals.
Genomic Imprinting: Intricacies of Epigenetic Regulation in Clusters
Authors: Verona Raluca I. , Mann Mellissa R.W. , Bartolomei Marisa S.
Published: October 2003

▪ Abstract  An intriguing characteristic of imprinted genes is that they often cluster in large chromosomal domains, raising the possibility that gene-specific and domain-specific mechanisms regulate imprinting. Several common features emerged from comparative analysis of four imprinted domains in mice and humans: (a) Certain genes appear to be imprinted by secondary events, possibly indicating a lack of gene-specific imprinting marks; (b) some genes appear to resist silencing, predicting the presence of cis-elements that oppose domain-specific imprinting control; (c) the nature of the imprinting mark remains incompletely understood. In addition, common silencing mechanisms are employed by the various imprinting domains, including silencer elements that nucleate and propagate a silent chromatin state, insulator elements that prevent promoter-enhancer interactions when hypomethylated on one parental allele, and antisense RNAs that function in silencing the overlapping sense gene and more distantly located genes. These commonalities are reminiscent of the behavior of genes subjected to, and the mechanisms employed in, dosage compensation.
Estrogen Receptor-α Polymorphisms and Angiographic Outcome After Coronary Artery Stenting
Authors: Ferrero Valeria , Ribichini Flavio , Matullo Giuseppe , Guarrera Simonetta , Carturan Sonia , Vado Antonello , Vassanelli Corrado , Piazza Alberto , Uslenghi Eugenio , Wijns William
Published: October 2003

Objective—Because of the receptor-mediated antiproliferative effects of estradiol on vascular smooth muscle cells, our study aimed at identifying a role of PvuII and XbaI polymorphisms of the α-estrogen receptor (αER) gene in the occurrence of restenosis after coronary stent implantation (in-stent restenosis [ISR]).

Methods and Results—In 858 patients (148 women), 955 lesions were treated with stent implantation, and the PvuII C/T and XbaI G/A polymorphisms of the αER gene were determined. Quantitative angiography was performed before and after stenting and at 6-month follow-up. The allelic frequencies were similar between sexes (C/T allele, 0.43/0.57 and 0.44/0.56;P=0.9; G/A allele, 0.35/0.65 and 0.38/0.62;P=0.8; in women and men, respectively). A significantly higher ISR rate in women than in men homozygous for the T-allele of the PvuII polymorphism (42.6% versus 26.9%,P=0.03) or the G-allele of the XbaI polymorphism (41.2% versus 19.4%,P=0.04) was observed. At multivariate analysis, T/T genotype was the only independent predictor of ISR in women but not in men (odds ratio, 1.5; 95% CI, 1.0 to 2.1;P=0.03). XbaI polymorphism was no longer associated with ISR in both sexes.

Conclusions—Women homozygous for the T-allele of the PvuII polymorphism of the αER gene treated with coronary stent implantation have a higher risk of ISR than men.
Alcohol Consumption and Carotid Atherosclerosis in Older Adults
Authors: Mukamal Kenneth J. , Kronmal Richard A. , Mittleman Murray A. , O’Leary Daniel H. , Polak Joseph F. , Cushman Mary , Siscovick David S.
Published: October 2003

Objective—

The association of alcohol use with atherosclerosis is inconsistent in previous studies.

Methods and Results—

For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonography to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values cross-sectionally using linear regression to adjust for demographic and clinical characteristics. Among 4247 participants free of cardiovascular disease, consumers of 1 to 6 drinks per week had 0.07±0.04-mm lower composite IMT and consumers of 14 or more drinks per week had 0.07±0.05-mm higher IMT than abstainers (
P
quadratic trend=0.02). We found similar relationships using internal and common carotid thickness measures and among men and women. The higher IMT associated with heavier alcohol use was particularly strong among 1592 participants with confirmed cardiovascular disease (0.24±0.09 mm greater than abstainers). Controlling for HDL cholesterol levels reduced the effect on composite IMT among consumers of 1 to 6 drinks per week by 22%.

Conclusions—

Relative to older adults who abstain from alcohol, consumption of 1 to 6 drinks per week had an inverse association with carotid atherosclerosis whereas consumption of 14 or more drinks had a positive association.
Association of the Toll-Like Receptor 4 Gene Asp299Gly Polymorphism With Acute Coronary Events
Authors: Ameziane Nejma , Beillat Tiphaine , Verpillat Patrice , Chollet-Martin Sylvie , Aumont Marie-Claude , Seknadji Patrick , Lamotte Maryse , Lebret Dominique , Ollivier Véronique , de Prost Dominique
Published: October 2003

Objective—

Atherosclerosis is a chronic inflammatory disease of the blood vessels. Toll-like receptor 4 (TLR4) is a transmembrane receptor that is involved in mediating inflammatory responses to bacterial endotoxin and other ligands. The aim of this study was to search for an association between a common functional polymorphism of TLR4 —Asp299Gly—and acute coronary syndrome.

Methods and Results—

We conducted a case-control study of 183 patients with acute coronary syndromes and 216 controls. We screened the TLR4 gene for the Asp299Gly polymorphism using a 5′ fluorogenic assay. The 299Gly allele was associated with a decreased risk of acute coronary events independently of standard coronary risk factors. The adjusted odds ratio associated with this allele was 0.41 (95% CI, 0.18 to 0.95;
P
=0.037). In controls, TLR4 heterozygosity was also associated with a significant decrease in plasma fibrinogen and soluble vascular cellular adhesion molecule-1 levels (
P
<0.01).

Conclusions—

These results, which must be confirmed by a prospective longitudinal study, provide evidence of an association between the Asp299Gly polymorphism of the human TLR4 receptor and acute coronary syndromes. They confirm the previously reported involvement of TLR4 in carotid and femoral artery atherosclerosis.
Angiogenesis Induced by Endothelial Nitric Oxide Synthase Gene Through Vascular Endothelial Growth Factor Expression in a Rat Hindlimb Ischemia Model
Authors: Namba Tsunetatsu , Koike Hiromi , Murakami Kazushi , Aoki Motokuni , Makino Hirofumi , Hashiya Naotaka , Ogihara Toshio , Kaneda Yasufumi , Kohno Masakazu , Morishita Ryuichi
Published: October 2003

Background—

Because the mechanism of the angiogenic property of nitric oxide (NO) was not fully understood in vivo, we focused on the role of vascular endothelial growth factor (VEGF) in angiogenesis induced by endothelial NO synthase (eNOS) gene transfer.

Methods and Results—

After intramuscular injection of eNOS DNA into a rat ischemic hindlimb, transfection of eNOS vector resulted in a significant increase in eNOS protein 1 week after transfection. In addition, tissue concentrations of nitrite and nitrate were significantly increased in rats transfected with the eNOS gene up to 2 weeks after transfection. The increase in tissue nitrite and nitrate concentrations was completely inhibited by
N
G
-nitro-
l
-arginine methyl ester (L-NAME). In contrast, serum concentrations of nitrite and nitrate and blood pressure were not changed by eNOS gene transfer. Importantly, overexpression of the eNOS gene resulted in a significant increase in peripheral blood flow, whereas L-NAME inhibited the increase in blood flow. Interestingly, basal blood flow was significantly lower in rats treated with L-NAME than in control rats. A significant increase in capillary number was consistently detected in rats transfected with the eNOS gene at 4 weeks after transfection, accompanied by a significant increase in VEGF. Moreover, administration of neutralizing anti-VEGF antibody abolished the increase in blood flow and capillary density induced by eNOS plasmid injection.

Conclusions—

Overall, intramuscular injection of bovine eNOS plasmid induced therapeutic angiogenesis in a rat ischemic hindlimb model, a potential therapy for peripheral arterial disease. The stimulation of angiogenesis by NO might be due to upregulation of local VEGF expression.
Anatomic Stereotactic Catheter Ablation on Three-Dimensional Magnetic Resonance Images in Real Time
Authors: Dickfeld Timm , Calkins Hugh , Zviman Muz , Kato Ritsushi , Meininger Glenn , Lickfett Lars , Berger Ron , Halperin Henry , Solomon Stephen B.
Published: October 2003

Background—

Targets for radiofrequency (RF) ablation of atrial fibrillation, atrial flutter, and nonidiopathic ventricular tachycardia are increasingly being selected on the basis of anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures and is associated with radiation risk, other approaches to mapping may be beneficial.

Methods and Results—

An electromagnetic catheter positioning system was superimposed on 3D MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MR images in real time. In vitro accuracy and precision during catheter navigation were assessed in a phantom model and were 1.11±0.06 and 0.30±0.07 mm (mean±SEM), respectively. Left and right heart catheterization was performed in 7 swine without the use of fluoroscopy, yielding an in vivo accuracy and precision of 2.74±0.52 and 1.97±0.44 mm, respectively. To assess the reproducibility of RF ablation, RF lesions were created repeatedly at the identical anatomic site in the right atrium (n=8 swine). Average distance of the repeated right atrial ablations was 3.92±0.5 mm. Straight 3-point lines were created in the right and left ventricles to determine the ability to facilitate complex ablation procedures (n=6 swine). The ventricular lesions deviated 1.70±0.24 mm from a straight line, and the point distance differed by 2.25±0.63 mm from the pathological specimen.

Conclusions—

Real-time display of the catheter position on 3D MRI allows accurate and precise RF ablation guided by the true anatomy. This may facilitate anatomically based ablation procedures in, for instance, atrial fibrillation or nonidiopathic ventricular tachycardia and decrease radiation times.
Opposing Effects Mediated by the Chemokine Receptor CXCR2 on Myocardial Ischemia-Reperfusion Injury
Authors: Tarzami Sima T. , Miao Wenfeng , Mani Kartik , Lopez Lillie , Factor Stephen M. , Berman Joan W. , Kitsis Richard N.
Published: October 2003

Background—

The timely reperfusion of ischemic myocardium limits infarction, but components of reperfusion, such as inflammation, may be injurious. The chemokine receptor CXCR2 mediates neutrophil chemotaxis. CXCR2 activation also inhibits hypoxia-induced death of isolated cardiac myocytes. This study assesses whether CXCR2 mediates protection in the intact heart and, if so, the magnitude of this protection relative to CXCR2-mediated chemotaxis of potentially damaging inflammatory cells.

Methods and Results—

After ischemia-reperfusion in vivo,
CXCR2
−/−
mice exhibited infarcts that were 50.5% smaller (
P
<0.05) with 44.3% fewer inflammatory cells (
P
<0.05) than
wild type
mice. These data suggest that in this model, CXCR2-mediated chemotaxis may be important in myocardial cell death. To isolate the role of CXCR2 specifically on blood cells, adoptive transfer experiments were performed. After ischemia-reperfusion, infarcts were 53.4% smaller (
P
<0.05) and contained 65.0% fewer inflammatory cells (
P
<0.05) in lethally irradiated
wild type
mice reconstituted with
CXCR2
−/−
compared with
wild type
bone marrow. Thus, CXCR2 on blood cells is important in myocardial damage, most likely because of CXCR2-mediated chemotaxis. To unmask whether CXCR2 mediates direct myocardial protection in the intact heart,
wild type
and
CXCR2
−/−
hearts were studied in the absence of blood using Langendorff preparations. In this case, infarcts were 19.7% larger in
CXCR2
−/−
than
wild type
hearts (
P
<0.05), revealing a novel CXCR2-mediated cardioprotective effect.

Conclusions—

CXCR2 exerts opposing effects on myocardial viability during ischemia-reperfusion with recruitment of damaging inflammatory cells predominant over direct tissue protection.
Evidence for a Functional Role of Angiotensin II Type 2 Receptor in the Cardiac Hypertrophic Process In Vivo in the Rat Heart
Authors: Lakó-Futó Zoltán , Szokodi István , Sármán Balázs , Földes Gábor , Tokola Heikki , Ilves Mika , Leskinen Hanna , Vuolteenaho Olli , Skoumal Réka , deChâtel Rudolf , Ruskoaho Heikki , Tóth Miklós
Published: October 2003

Background—

The precise function of angiotensin II type 2 receptor (AT
2
-R) in the mammalian heart in vivo is unknown. Here, we investigated the role of AT
2
-R in cardiac pressure overload.

Methods and Results—

Rats were infused with vehicle, angiotensin II (Ang II), PD123319 (an AT
2
-R antagonist), or the combination of Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72 hours. Ang II–induced increases in mean arterial pressure, left ventricular weight/body weight ratio, and elevation of skeletal α-actin and β-myosin heavy chain mRNA levels were not altered by PD123319. In contrast, AT
2
-R blockade resulted in a marked increase in the gene expression of c-fos, endothelin-1, and insulin-like growth factor-1 in Ang II–induced hypertension. In parallel, Ang II–stimulated mRNA and protein expression of atrial natriuretic peptide were significantly augmented by AT
2
-R blockade. Moreover, PD123319 markedly increased the synthesis of B-type natriuretic peptide. Furthermore, the expression of vascular endothelial growth factor and fibroblast growth factor-1 was downregulated by Ang II only in the presence of AT
2
-R blockade.

Conclusions—

Our results provide evidence that AT
2
-R plays a functional role in the cardiac hypertrophic process in vivo by selectively regulating the expression of growth-promoting and growth-inhibiting factors.
Enhanced Therapeutic Angiogenesis by Cotransfection of Prostacyclin Synthase Gene or Optimization of Intramuscular Injection of Naked Plasmid DNA
Authors: Hiraoka Kazuya , Koike Hiromi , Yamamoto Seiji , Tomita Naruya , Yokoyama Chieko , Tanabe Tadashi , Aikou Takashi , Ogihara Toshio , Kaneda Yasufumi , Morishita Ryuichi
Published: October 2003

Background—

Although clinical trials of therapeutic angiogenesis by angiogenic growth factors with intramuscular injection of naked plasmid DNA have been successful, there are still unresolved problems such as low transfection efficiency. From this viewpoint, we performed the following modifications: (1) combination with vasodilation using prostacyclin and (2) changing the agents or volume of naked plasmid DNA in vivo.

Methods and Results—

First, we examined cotransfection of the
VEGF
gene with the prostacyclin synthase gene in a mouse hindlimb ischemia model. Cotransfection of the
VEGF
gene with the prostacyclin synthase gene resulted in a further increase in blood flow and capillary density compared with single
VEGF
gene. Similar results were obtained with other angiogenic growth factors, such as hepatocyte growth factor (HGF). Alternatively, we changed the injection volume of the solution of plasmid DNA. Luciferase activity was increased in a volume-dependent manner. An increase in injection volume at 1 site rather than separate injections at multiple sites resulted in high transfection efficiency, which suggests that transfection of naked plasmid DNA is mediated by pressure. Interestingly, treatment with hyperbaric oxygen increased the transfection efficiency. Finally, we also examined the effects of different solutions. Saline and PBS, but not water, achieved high transfection efficiency. In addition, sucrose solution but not glucose solution resulted in high luciferase activity.

Conclusions—

Overall, angiogenesis might be enhanced by cotransfection of prostacyclin synthase gene or an increase in injection volume and osmotic pressure. These data provide important information for the clinical application of therapeutic angiogenesis to treat peripheral arterial disease.
Practical Value of Cardiac Magnetic Resonance Imaging for Clinical Quantification of Aortic Valve Stenosis
Authors: Caruthers Shelton D. , Lin Shiow Jiuan , Brown Peggy , Watkins Mary P. , Williams Todd A. , Lehr Katherine A. , Wickline Samuel A.
Published: October 2003

Background—

Valvular pathology can be analyzed quickly and accurately through the use of Doppler ultrasound. For aortic stenosis, the continuity equation approach with Doppler velocity-time integral (VTI) data is by far the most commonly used clinical method of quantification. In view of the emerging popularity of cardiac magnetic resonance (CMR) as a routine clinical imaging tool, the purposes of this study were to define the reliability of velocity-encoded CMR as a routine method for quantifying stenotic aortic valve area, to compare this method with the accepted standard, and to evaluate its reproducibility.

Methods and Results—

Patients (n=24) with aortic stenosis (ranging from 0.5 to 1.8 cm
2
) were imaged with CMR and echocardiography. Velocity-encoded CMR was used to obtain velocity information in the aorta and left ventricular outflow tract. From this flow data, pressure gradients were estimated by means of the modified Bernoulli equation, and VTIs were calculated to estimate aortic valve orifice dimensions by means of the continuity equation. The correlation coefficients between modalities for pressure gradients were
r
=0.83 for peak and
r
=0.87 for mean. The measurements of VTI correlated well, leading to an overall strong correlation between modalities for the estimation of valve dimension (
r
=0.83, by means of the identified best approach). For 5 patients, the CMR examination was repeated using the best approach. The repeat calculations of valve size correlated well (
r
=0.94).

Conclusions—

Velocity-encoded CMR can be used as a reliable, user-friendly tool to evaluate stenotic aortic valves. The measurements of pressure gradients, VTIs, and the valve dimension correlate well with the accepted standard of Doppler ultrasound.
Comparison of Standard Cardiopulmonary Resuscitation Versus the Combination of Active Compression-Decompression Cardiopulmonary Resuscitation and an Inspiratory Impedance Threshold Device for Out-of-Hospital Cardiac Arrest
Authors: Wolcke Benno B. , Mauer Dietmar K. , Schoefmann Mark F. , Teichmann Heinke , Provo Terry A. , Lindner Karl H. , Dick Wolfgang F. , Aeppli Dorothee , Lurie Keith G.
Published: October 2003

Background—

Active compression-decompression (ACD) CPR combined with an inspiratory impedance threshold device (ITD) improves vital organ blood flow during cardiac arrest. This study compared survival rates with ACD+ITD CPR versus standard manual CPR (S-CPR).

Methods and Results—

A prospective, controlled trial was performed in Mainz, Germany, in which a 2-tiered emergency response included early defibrillation. Patients with out-of-hospital arrest of presumed cardiac pathogenesis were sequentially randomized to ACD+ITD CPR or S-CPR by the advanced life support team after intubation. Rescuers learned which method of CPR to use at the start of each work shift. The primary end point was 1-hour survival after a witnessed arrest. With ACD+ITD CPR (n=103), return of spontaneous circulation and 1- and 24-hour survival rates were 55%, 51%, and 37% versus 37%, 32%, and 22% with S-CPR (n=107) (
P
=0.016, 0.006, and 0.033, respectively). One- and 24-hour survival rates in witnessed arrests were 55% and 41% with ACD+ITD CPR versus 33% and 23% in control subjects (
P
=0.011 and 0.019), respectively. One- and 24-hour survival rates in patients with a witnessed arrest in ventricular fibrillation were 68% and 58% after ACD+ITD CPR versus 27% and 23% after S-CPR (
P
=0.002 and 0.009), respectively. Patients randomized ≥10 minutes after the call for help to the ACD+ITD CPR had a 3 times higher 1-hour survival rate than control subjects (
P
=0.002). Hospital discharge rates were 18% after ACD+ITD CPR versus 13% in control subjects (
P
=0.41). In witnessed arrests, overall neurological function trended higher with ACD+ITD CPR versus control subjects (
P
=0.07).

Conclusions—

Compared with S-CPR, ACD+ITD CPR significantly improved short-term survival rates for patients with out-of-hospital cardiac arrest. Additional studies are needed to evaluate potential long-term benefits of ACD+ITD CPR.
Anaphylactic and Anaphylactoid Reactions Associated With Lepirudin in Patients With Heparin-Induced Thrombocytopenia
Authors: Greinacher A. , Lubenow N. , Eichler P.
Published: October 2003

Background—

Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis.

Methods and Results—

Aided by the manufacturer (Schering AG, Berlin, Germany), we used the lepirudin study databases to identify all patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to September 2002. The 26 possible cases identified were reviewed independently by 2 investigators. After excluding patients with mild skin reactions, reactions likely caused by concomitant medications, poorly documented cases, and reactions that did not correspond temporally with lepirudin use, there remained 9 patients judged to have had severe anaphylaxis in close temporal association with lepirudin. All reactions occurred within minutes of intravenous lepirudin administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1 hypotension-induced myocardial infarction). In these 4 cases, a previous uneventful treatment course with lepirudin was identified (1 to 12 weeks earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional patient with anaphylaxis. Because lepirudin has been used in ≈35 000 patients, the risk of anaphylaxis is ≈0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures).

Conclusion—

Lepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.
Mobilized Endothelial Progenitor Cells by Granulocyte-Macrophage Colony-Stimulating Factor Accelerate Reendothelialization and Reduce Vascular Inflammation After Intravascular Radiation
Authors: Cho Hyun-Jai , Kim Hyo-Soo , Lee Myoung-Mook , Kim Dae-Hee , Yang Hyun-Ju , Hur Jin , Hwang Kyoung-Kook , Oh Seil , Choi Young-Jin , Chae In-Ho , Oh Byung-Hee , Choi Yun-Shik , Walsh Kenneth , Park Young-Bae
Published: October 2003

Background—

Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy.

Methods and Results—

One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 μg/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81±13% in the GM-CSF radiation [n=7] versus 30±11% in the control radiation [n=9] at 2 weeks,
P
<0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14±0.11 in the GM-CSF radiation [n=5] versus 0.36±0.07 in the control radiation [n=5] at 4 weeks,
P
<0.01).

Conclusions—

GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.
Transdifferentiation of Human Peripheral Blood CD34
+
-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo
Authors: Yeh Edward T.H. , Zhang Sui , Wu Henry D. , Körbling Martin , Willerson James T. , Estrov Zeev
Published: October 2003

Background—

Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial cells of the skin and gastrointestinal track. We investigated whether these cells could also transdifferentiate into human cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo.

Methods and Results—

Myocardial infarction was created in SCID mice by occluding the left anterior descending coronary artery, after which adult peripheral blood CD34
+
cells were injected into the tail vein. Hearts were harvested 2 months after injection and stained for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth muscle cells that bear HLA were identified in the infarct and peri-infarct regions of the mouse hearts. In a separate experiment, CD34
+
cells were injected intraventricularly into mice without experimental myocardial infarction. HLA-positive myocytes and smooth muscle cells could only be identified in 1 of these mice killed at different time points.

Conclusions—

Adult peripheral blood CD34
+
cells can transdifferentiate into cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. However, transdifferentiation is augmented significantly by local tissue injury. The use of peripheral blood CD34
+
cells for cell-based therapy should greatly simplify the procurement of cells for the regeneration of damaged myocardium.