bluuebunny/crossref_metadata_2025 huggingface dataset:
A FUZZY LOGIC AND DEFAULT REASONING MODEL OF SOCIAL NORMS AND EQUILIBRIUM SELECTION IN GAMES UNDER UNFORESEEN CONTINGENCIES
Authors: SACCONI LORENZO , MORETTI STEFANO
Published: February 2008

This paper focuses on the role that social norms play in the selection of equilibrium points seen as social conventions under unforeseen contingencies — that is, their role in the emergence of regularities of behavior which are self-enforcing and effectively adhered to by bounded rational agents due to their self-policing incentives. Differently stated, given a set of game situations imperfectly described, we want to understand how general and abstract norms provide at least the starting point for a norm-based equilibrium selection reasoning procedure which in the end will be able to determine which equilibrium point, belonging to perfectly described games, will be played as the unique solution of each imperfectly described game. In order to solve such a problem we introduce a selection process based on the reformulation of default logic in terms of possibility theory.
ON PARA-NORMED SPACE WITH FUZZY VARIABLES BASED ON EXPECTED VALUED OPERATOR
Authors: ZHU YUANGUO
Published: February 2008

Fuzzy variables are functions from credibility spaces to the set of real numbers. The set of fuzzy variables is a linear space with the classic operations of addition and multiplication by numbers. Its subspace formed by fuzzy variables with finite pth absolute moments is showed to be a complete para-normed space. The concept of para-normed space is novel, and is an extension of normed space. It is seen that most properties of normed spaces hold in para-normed spaces. Also some useful inequalities in para-normed spaces are obtained.
A NEW APPROACH FOR PROBABILISTICALLY BOUNDED SETS IN MENGER PROBABILISTIC NORMED SPACES
Authors: YAN CONG-HUA
Published: February 2008

The main purpose of this paper is to introduce a new topological structure which is called fuzzifying topological structure determined by the method of co-tower topologies in Menger probabilistic normed spaces. We prove that the fuzzifying topological structure is compatible with the vector structure. A characterization of probabilistically bounded sets in Menger probabilistic normed spaces is obtained.
PERMANENCE IN A DISCRETE n-SPECIES NON-AUTONOMOUS LOTKA–VOLTERRA COMPETITIVE SYSTEMS WITH INFINITE DELAYS AND FEEDBACK CONTROL
Authors: CHEN XIAOXING
Published: February 2008

In this paper, we deal with a discrete n-species non-autonomous Lotka–Volterra competitive systems with infinite delays and feedback control, obtain sufficient conditions for the permanence of the systems.
GLOBAL PROPERTIES OF A MODEL OF IMMUNE EFFECTOR RESPONSES TO VIRAL INFECTIONS
Authors: WANG XIA , SONG XINYU
Published: February 2008

This article proposes a mathematical model which has been used to investigate the importance of lytic and non-lytic immune responses for the control of viral infections. By means of Lyapunov functions, the global properties of the model are obtained. The virus is cleared if the basic reproduction number R0 ≤ 1 and the virus persists in the host if R0 > 1. Furthermore, if R0 > 1 and other conditions hold, the immune-free equilibrium E0 is globally asymptotically stable. The equilibrium E1 exists and is globally asymptotically stale if the CTL immune response reproductive number R1 < 1 and the antibody immune response reproductive number R2 > 1. The equilibrium E2 exists and is globally asymptotically stable if R1 > 1 and R2 < 1. Finally, the endemic equilibrium E3 exists and is globally asymptotically stable if R1 > 1 and R2 > 1.
OPEN SYNCHRONOUS CELLULAR LEARNING AUTOMATA
Authors: BEIGY HAMID , MEYBODI M. R.
Published: February 2008

Cellular learning automata is a combination of learning automata and cellular automata. This model is superior to cellular learning automata because of its ability to learn and also is superior to single learning automaton because it is a collection of learning automata which can interact together. In some applications such as image processing, a type of cellular learning automata in which the action of each cell in the next stage of its evolution not only depends on the local environment (actions of its neighbors) but it also depends on the external environments. We call such a cellular learning automata as open cellular learning automata. In this paper, we introduce open cellular learning automata and then study its steady state behavior. It is shown that for a class of rules called commutative rules, the open cellular learning automata in stationary external environments converges to a stable and compatible configuration. Then the application of this new model to image segmentation has been presented.
A CONCERTED ACTION OF B CELL SELECTION MECHANISMS
Authors: MEYER–HERMANN MICHAEL
Published: February 2008

Mathematical modeling of complex biological systems has been shown to lead to contradictory results. Two completely different approaches are compared using a highly dynamic system of the adaptive immune response with medical relevance. In germinal centers, high affinity antibodies are newly generated from antigen-activated B cell clones. The encoded antibody is mutated and high affinity clones for a specific antigen are selected to survive, giving rise to affinity maturation of antibodies. Here, the general assumption that competition for antigen held on follicular dendritic cells is responsible for affinity maturation is shown to be unlikely. This finding is based on the investigation of eight different selection mechanisms. A realistic model on selection mechanisms leading to affinity maturation is developed. It is found that negative selection of B cell, a B cell refractory time for binding antigen, and competition for T cell help, have strongest impact on affinity maturation. Antigen consumption is demonstrated to have impact on the kinetics of the germinal center in the late phase of the reaction and is hypothesized to be responsible for the termination of the reaction. These results are consistently found with agent-based and ordinary differential equation approaches and can, thus be considered to be robust. Experimental tests of the predicted selection mechanisms are proposed.
NONLINEAR DETERMINISTIC ANALYSIS OF AIR POLLUTION DYNAMICS IN A RURAL AND AGRICULTURAL SETTING
Authors: SIVAKUMAR BELLIE , WALLENDER WESLEY W. , HORWATH WILLIAM R. , MITCHELL JEFFREY P.
Published: February 2008

Applications of nonlinear dynamic tools for studying air pollution are gaining attention. Studies on ozone concentration in urban areas have reported the presence of low-dimensional deterministic natures and thus the possibility of good predictions of air pollution dynamics. In light of these encouraging results, a nonlinear deterministic approach is employed herein to study air pollution dynamics in a rural, and largely agricultural, setting in California. Specifically, air quality index (AQI) data observed at the University of California, Davis/National Oceanic and Atmospheric Administration (UCD/NOAA) climate station are studied. Four different daily AQI types of data are analyzed: maximum, minimum, difference (between maximum and minimum), and average. The correlation dimension method, a nonlinear dynamic technique that uses phase–space reconstruction and nearest neighbor concepts, is employed to identify the nature of the underlying dynamics, whether high-dimensional or low-dimensional. Correlation dimensions of 5.12, 6.20, 6.68, and 5.84 obtained for the above four series, respectively, indicate the presence of low-dimensional deterministic behavior, with six or seven dominant governing variables in the underlying dynamics. The dimension results and number of variables are in reasonable agreement with those reported by past studies, even though the studied data are different: rural versus urban, and AQI versus ozone concentration. Future efforts will focus on strengthening the present results on the nature of air pollution dynamics, identifying the actual governing variables, and predictions of air pollution dynamics.
WOLSTENHOLME TYPE THEOREM FOR MULTIPLE HARMONIC SUMS
Authors: ZHAO JIANQIANG
Published: February 2008

In this paper, we will study the p-divisibility of multiple harmonic sums (MHS) which are partial sums of multiple zeta value series. In particular, we provide some generalizations of the classical Wolstenholme's Theorem to both homogeneous and non-homogeneous sums. We make a few conjectures at the end of the paper and provide some very convincing evidence.
p-ADIC PERIODS OF MODULAR ELLIPTIC CURVES AND THE LEVEL-LOWERING THEOREM
Authors: TAKAHASHI S.
Published: February 2008

An elliptic curve defined over the field of rational numbers can be considered as a complex torus. We can describe its complex periods in terms of integration of the weight-2 cusp form corresponding to the elliptic curve. In this paper, we will study an analogous description of the p-adic periods of the elliptic curve, considering the elliptic curve as a p-adic torus. An essential tool for the proof of such a description is the level-lowering theorem of Ribet, which is one of the main ingredients used in the proof of Fermat's Last Theorem.
ON DAVENPORT'S CONSTANT
Authors: RATH P. , SRILAKSHMI K. , THANGADURAI R.
Published: February 2008

In this paper, using the idea of Alford, Granville and Pomerance in [1] (or van Emde Boas and Kruyswijk [6]), we obtain an upper bound for the Davenport Constant of an Abelian group G in terms of the number of repetitions of the group elements in any given sequence. In particular, our result implies, [Formula: see text] where n is the exponent of G and k ≥ 0 denotes the number of distinct elements of G that are repeated at least twice in the given sequence.
ARITHMETICAL RESULTS ON CERTAIN q-SERIES, I
Authors: BUNDSCHUH PETER
Published: February 2008

Entire transcendental solutions of certain mth order linear q-difference equations with polynomial coefficients are considered. The aim of this paper is to give, under appropriate arithmetical conditions, lower bounds for the dimension of the K-vector space generated by 1 and the values of these solutions at m successive powers of q, where K is the rational or an imaginary quadratic number field. The main ingredients of the proofs are, first, Nesterenko's dimension estimate and its various generalizations, and secondly, Popov's method (in Töpfer's version) for the asymptotic evaluation of certain complex integrals.
ON CONJUGATES OF COLLATZ-TYPE MAPPINGS
Authors: KOHL STEFAN
Published: February 2008

A mapping f : ℤ → ℤ is called residue-class-wise affine if there is a positive integer m such that it is affine on residue classes (mod m). If there is a finite set S ⊂ ℤ which intersects nontrivially with any trajectory of f, then f is called almost contracting. Assume that f is a surjective but not injective residue-class-wise affine mapping, and that the preimage of any integer under f is finite. Then f is almost contracting if and only if there is a permutation σ of ℤ such that fσ = σ-1 ◦ f ◦ σ is either monotonically increasing or monotonically decreasing almost everywhere. In this paper it is shown that if there is no positive integer k such that applying f(k) decreases the absolute value of almost all integers, then σ cannot be residue-class-wise affine itself. The original motivation for the investigations in this paper comes from the famous 3n + 1 Conjecture.
ON A FAMILY OF THREE TERM NONLINEAR INTEGER RECURRENCES
Authors: KIRSCHENHOFER P. , PETHŐ A. , THUSWALDNER J. M.
Published: February 2008

In the present paper we study sequences defined by the recurrence relation [Formula: see text] for n ≥ 0, where [Formula: see text] the golden ratio. These sequences are related to shift radix systems as well as to β-expansions with respect to Salem numbers.
A FAMILY OF ASYMPTOTICALLY GOOD LATTICES HAVING A LATTICE IN EACH DIMENSION
Authors: INTERLANDO J. CARMELO , FLORES ANDRÉ LUIZ , DA NÓBREGA NETO TRAJANO PIRES
Published: February 2008

A new constructive family of asymptotically good lattices with respect to sphere packing density is presented. The family has a lattice in every dimension n ≥ 1. Each lattice is obtained from a conveniently chosen integral ideal in a subfield of the cyclotomic field ℚ(ζq) where q is the smallest prime congruent to 1 modulo n.
The Seismic Structure and Dynamics of the Mantle Wedge
Authors: Wiens Douglas A. , Conder James A. , Faul Ulrich H.
Published: February 2008

Seismic imaging provides an opportunity to constrain mantle wedge processes associated with subduction, slab dehydration, arc volcanism, and backarc spreading. The mantle wedge is characterized by a low attenuation forearc, an inclined zone of low velocity and high attenuation underlying the volcanic front, and a broad region of low velocity and high attenuation beneath the backarc spreading center when present. Seismic velocities, bathymetry, and basalt chemistry suggest mantle temperature variations of ∼100°C between different backarc regions. Rock physics experiments and geodynamic modeling are essential for interpreting seismic observations. Seismic anisotropy indicates a complex pattern of mantle flow that can be modeled with along-strike flow in a low viscosity channel beneath the arc and backarc. Comparison of geodynamic models with seismic tomographic results using experimentally derived relations between velocity, attenuation, and temperature suggests the existence of small melt fractions in the mantle at depths of 30–150 km.
Modeling the Dynamics of Subducting Slabs
Authors: Billen Magali I.
Published: February 2008

Cold, dense subducting lithosphere provides the primary force driving tectonic plates at Earth's surface. The force available to drive the plates depends on a balance between the buoyancy forces driving subduction and the mechanical and buoyancy forces resisting subduction. Because both the buoyancy and rheology of the slab and mantle depend on temperature, composition, grain size, water content, and melt fraction, unraveling which of these processes exert a first-order control on slab dynamics and under what circumstances other processes become first-order effects can be challenging. Laboratory and numerical models of slab dynamics provide a powerful method for testing the combined effects of buoyancy and strength changes that accompany the slab evolution in the upper mantle, transition zone, and lower mantle. Recent studies have focused on understanding how rheologic variations (Newtonian versus non-Newtonian viscosity or water content), geometry (2D versus 3D), and plate motions (trench roll-back or advance) influence the evolution of slabs in the upper mantle and how they sink into the lower mantle. These models suggest that spatial and temporal variations in slab strength and the history of subduction determine whether slabs sink directly into the lower mantle or are trapped in the transition zone.
The Redox State of Earth's Mantle
Authors: Frost Daniel J. , McCammon Catherine A.
Published: February 2008

Oxygen thermobarometry measurements on spinel peridotite rocks indicate that the oxygen fugacity at the top of the upper mantle falls within ±2 log units of the fayalite-magnetite-quartz (FMQ) oxygen buffer. Measurements on garnet peridotites from cratonic lithosphere reveal a general decrease in fo2 with depth, which appears to result principally from the effect of pressure on the controlling Fe3+/Fe2+ equilibria. Modeling of experimental data indicates that at approximately 8 GPa, mantle fo2 will be 5 log units below FMQ and at a level where Ni-Fe metal becomes stable. Fe-Ni alloy and an Fe2O3-garnet component will be formed as a result of the disproportionation of FeO, which is experimentally demonstrated through observations of high Fe3+/ΣFe ratios in minerals in equilibrium with metallic Fe. In the lower mantle, the favorable coupled substitution of Al and Fe3+ into (Fe,Mg)SiO3 perovskite results in very high perovskite Fe3+/ΣFe ratios in equilibrium with metallic Fe. As a result, the lower mantle should contain approximately 1 weight% metallic Fe formed through FeO disproportionation, if the bulk oxygen content is the same as the upper mantle. Loss of disproportionated metallic Fe from the lower mantle during core formation could explain the higher Fe3+/ΣFe ratio of the present-day upper mantle when compared to that expected during core formation. The influence of pressure on mantle fo2 has important implications for the speciation of C-O-H-S volatile phases in Earth today and during its early evolution.
A general and islet cell-enriched overexpression of IGF-I results in normal islet cell growth, hypoglycemia, and significant resistance to experimental diabetes
Authors: Robertson Katie , Lu Yarong , De Jesus Kristine , Li Bing , Su Qing , Lund P. Kay , Liu Jun-Li
Published: February 2008

Insulin-like growth factor I (IGF-I) is normally produced from hepatocytes and various other cells and tissues, including the pancreas, and is known to stimulate islet cell replication in vitro, prevent Fas-mediated β-cell destruction and delay the onset of diabetes in nonobese diabetic mice. Recently, however, the notion that IGF-I stimulates islet cell growth has been challenged by the results of IGF-I and receptor gene targeting. To test the effects of a general, more profound increase in circulating IGF-I on islet cell growth and glucose homeostasis, we have characterized MT-IGF mice, which overexpress the IGF-I gene under the metallothionein I promoter. In early reports, a 1.5-fold-elevated serum IGF-I level caused accelerated somatic growth and pancreatic enlargement. We demonstrated that the transgene expression, although widespread, was highly concentrated in the β-cells of the pancreatic islets. Yet, islet cell percent and pancreatic morphology were unaffected. IGF-I overexpression resulted in significant hypoglycemia, hypoinsulinemia, and improved glucose tolerance but normal insulin secretion and sensitivity. Pyruvate tolerance test indicated significantly suppressed hepatic gluconeogenesis, which might explain the severe hypoglycemia after fasting. Finally, due to a partial prevention of β-cell death against onset of diabetes and/or the insulin-like effects of IGF-I overexpression, MT-IGF mice (which overexpress the IGF-I gene under the metallothionein I promoter) were significantly resistant to streptozotocin-induced diabetes, with diminished hyperglycemia and prevention of weight loss and death. Although IGF-I might not promote islet cell growth, its overexpression is clearly antidiabetic by improving islet cell survival and/or providing insulin-like effects.
A New Trick for an Old Dogma: ENaC Proteins as Mechanotransducers in Vascular Smooth Muscle
Authors: Drummond Heather A. , Grifoni Samira C. , Jernigan Nikki L.
Published: February 2008

Myogenic constriction is a vasoconstriction of blood vessels to increases in perfusion pressure. In renal preglomerular vasculature, it is an established mechanism of renal blood flow autoregulation. Recently, myogenic constriction has been identified as an important protective mechanism, preventing the transmission of systemic pressure to the fragile glomerular vasculature. Although the signal transduction pathways mediating vasoconstriction are well known, how the increases in pressure trigger vasoconstriction is unclear. The response is initiated by pressure-induced stretch of the vessel wall and thus is dependent on mechanical signaling. The identity of the sensor detecting VSMC stretch is unknown. Previous studies have considered the role of extracellular matrix-integrin interactions, ion conduction units (channels and/or transporters), and the cytoskeleton as pressure detectors. Whether, and how, these structures fit together in VSMCs is poorly understood. However, a model of mechanotransduction in the nematode Caenorhadbditis elegans ( C. elegans) has been established that ties together extracellular matrix, ion channels, and cytoskeletal proteins into a large mechanosensing complex. In the C. elegans mechanotransducer model, a family of evolutionarily conserved proteins, referred to as the DEG/ENaC/ASIC family, form the ion-conducting pore of the mechanotransducer. Members of this protein family are expressed in VSMC where they may participate in pressure detection. This review will address how the C. elegans mechanotransducer model can be used to model pressure detection in mammalian VSMCs and provide a new perspective to pressure detection in VSMCs.
Physiology of Nucleoside Transporters: Back to the Future. . . .
Authors: Rose Jennifer B. , Coe Imogen R.
Published: February 2008

Nucleoside transporters (NTs) are integral membrane proteins responsible for mediating and facilitating the flux of nucleosides and nucleobases across cellular membranes. NTs are also responsible for the uptake of nucleoside analog drugs used in the treatment of cancer and viral infections, and they are the target of certain compounds used in the treatment of some types of cardiovascular disease. The important role of NTs as drug transporters and therapeutic targets has necessarily led to intense interest into their structure and function and the relationship between these proteins and drug efficacy. In contrast, we still know relatively little about the fundamental physiology of NTs. In this review, we discuss various aspects of the physiology of NTs in mammalian systems, particularly noting tissues and cells where there has been little recent research. Our central thesis is reference back to some of the older literature, combined with current findings, will provide direction for future research into NT physiology that will lead to a fuller understanding of the role of these intriguing proteins in the everyday lives of cells, tissues, organs, and whole animals.
Mutation Variants Generated from Nonvirulent Coxsackievirus B3 Acquire Virulence Phenotypes by Active Virus Replication
Authors: Seo Ilseon , Jee Youngmee , Ahn Jeonghyun , Jun Eun Jung , Kim Donghou , Joo Chul Hyun , Kim Yoo Kyum , Lee Heuiran
Published: February 2008

Objective: To understand coxsackievirus B3 (CVB3) virulence at the molecular level. Method: A mutation library was generated from noncardiovirulent CVB3/0. Highly virulent mutation variants were recovered and characterized both phenotypically and genotypically. Results: The variants consistently caused destruction of multiple tissues together with active virus production and induced severe mortality in vivo. The extent of infectious virus generation was directly correlated with that of histopathological aberration. Genotypic analysis of the entire genome indicated that the virulent viruses encode nucleotide substitutions in the 5′-nontranslated region, which have previously been identified in other virulent CVB3s. Conclusion: The present study provides evidence that particular nucleotide substitutions in the 5′-nontranslated region of nonvirulent CVB3 can lead to active virus replication, which is sufficient to induce virulence.
Abdominal Aortic Aneurysms, Increasing Infrarenal Aortic Diameter, and Risk of Total Mortality and Incident Cardiovascular Disease Events
Authors: Freiberg Matthew S. , Arnold Alice M. , Newman Anne B. , Edwards Matthew S. , Kraemer Kevin L. , Kuller Lewis H.
Published: February 2008

Background—

Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse.

Methods and Results—

In 1992 to 1993, 4734 Cardiovascular Health Study participants ≥65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter ≥3.0 cm or an infrarenal/suprarenal ratio ≥1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation ≥3 cm identified 68% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4% of the total population and that a ≥2.5-cm dilation identified 91% of all AAA repairs and 9 of the 10 deaths in 10% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95% confidence interval 1.25 to 1.85). Compared with diameters <2.0 cm, infrarenal aortic diameters 2.0 to <3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men.

Conclusions—

This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters >2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.
Effects of Levosimendan on Left Ventricular Relaxation and Early Filling at Maintained Preload and Afterload Conditions After Aortic Valve Replacement for Aortic Stenosis
Authors: Jörgensen Kirsten , Bech-Hanssen Odd , Houltz Erik , Ricksten Sven-Erik
Published: February 2008

Background—We determined the effects of levosimendan, a calcium sensitizer, on left ventricular (LV) diastolic function in patients with LV hypertrophy.

Methods and Results—In this prospective, randomized, blinded study, 23 patients received either levosimendan (0.1 and 0.2 μg · kg−1· min−1; n=12) or placebo (n=11) after aortic valve replacement for aortic stenosis. The effects on LV performance, dimensions, filling patterns, and isovolumic relaxation time, as well as systemic hemodynamics, were assessed by pulmonary artery thermodilution catheterization and transesophageal 2-dimensional Doppler echocardiography. To circumvent the confounding effects of the levosimendan-induced hemodynamic changes on Doppler echocardiographic indexes of LV early relaxation, heart rate and mean arterial and central venous pressures were kept constant during levosimendan/placebo infusion by atrial pacing, vasopressor, and colloid infusions. In the levosimendan group, dose-dependent increases in cardiac output (28%;P<0.001) and stroke volume (26%;P<0.001) and a decrease in systemic vascular resistance (−22%;P<0.001) were observed. There was a trend for an increase in LV ejection fraction (12%;P=0.058) with levosimendan. There were no significant differences in systolic, diastolic arterial, or LV filling pressures or LV end-diastolic area between the 2 groups. Isovolumic relaxation time decreased (−23%;P<0.001), as did the deceleration slope of early diastolic filling (−45%;P<0.01), whereas peak early diastolic filling velocity (16%,P<0.01) and peak late diastolic filling velocity (15%;P<0.001) increased after levosimendan compared with placebo.

Conclusion—Levosimendan, in addition to its inotropic effects, exerts a direct positive lusitropic effect in patients with LV hypertrophy as it shortens isovolumic relaxation time and improves LV filling.
Effect of the Italian Smoking Ban on Population Rates of Acute Coronary Events
Authors: Cesaroni Giulia , Forastiere Francesco , Agabiti Nera , Valente Pasquale , Zuccaro Piergiorgio , Perucci Carlo A.
Published: February 2008

Background—

Several countries in the world have not yet prohibited smoking in public places. Few studies have been conducted on the effects of smoking bans on cardiac health. We evaluated changes in the frequency of acute coronary events in Rome, Italy, after the introduction of legislation that banned smoking in all indoor public places in January 2005.

Methods and Results—

We analyzed acute coronary events (out-of-hospital deaths and hospital admissions) between 2000 and 2005 in city residents 35 to 84 years of age. We computed annual standardized rates and estimated rate ratios by comparing the data from prelegislation (2000–2004) and postlegislation (2005) periods. We took into account several time-related potential confounders, including particulate matter (PM
10
) air pollution, temperature, influenza epidemics, time trends, and total hospitalization rates. The reduction in acute coronary events was statistically significant in 35- to 64-year-olds (11.2%, 95% CI 6.9% to 15.3%) and in 65- to 74-year-olds (7.9%, 95% CI 3.4% to 12.2%) after the smoking ban. No evidence was found of an effect among the very elderly. The reduction tended to be greater in men and among lower socioeconomic groups.

Conclusions—

We found a statistically significant reduction in acute coronary events in the adult population after the smoking ban. The size of the effect was consistent with the pollution reduction observed in indoor public places and with the known health effects of passive smoking. The results affirm that public interventions that prohibit smoking can have enormous public health implications.
Role of Caveolar Compartmentation in Endothelium-Derived Hyperpolarizing Factor–Mediated Relaxation
Authors: Saliez J. , Bouzin C. , Rath G. , Ghisdal P. , Desjardins F. , Rezzani R. , Rodella L.F. , Vriens J. , Nilius B. , Feron O. , Balligand J-L. , Dessy C.
Published: February 2008

Background—

In endothelial cells, caveolin-1, the structural protein of caveolae, acts as a scaffolding protein to cluster lipids and signaling molecules within caveolae and, in some instances, regulates the activity of proteins targeted to caveolae. Specifically, different putative mediators of the endothelium-derived hyperpolarizing factor (EDHF)–mediated relaxation are located in caveolae and/or regulated by the structural protein caveolin-1, such as potassium channels, calcium regulatory proteins, and connexin 43, a molecular component of gap junctions.

Methods and Results—

Comparing relaxation in vessels from caveolin-1 knockout mice and their wild-type littermates, we observed a complete absence of EDHF-mediated vasodilation in isolated mesenteric arteries from caveolin-1 knockout mice. The absence of caveolin-1 is associated with an impairment of calcium homeostasis in endothelial cells, notably, a decreased activity of Ca
2+
-permeable TRPV4 cation channels that participate in nitric oxide– and EDHF-mediated relaxation. Moreover, morphological characterization of caveolin-1 knockout and wild-type arteries showed fewer gap junctions in vessels from knockout animals associated with a lower expression of connexins 37, 40, and 43 and altered myoendothelial communication. Finally, we showed that TRPV4 channels and connexins colocalize with caveolin-1 in the caveolar compartment of the plasma membrane.

Conclusions—

We demonstrated that expression of caveolin-1 is required for EDHF-related relaxation by modulating membrane location and activity of TRPV4 channels and connexins, which are both implicated at different steps in the EDHF-signaling pathway.
Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System
Authors: Vasan Ramachandran S. , Demissie Serkalem , Kimura Masayuki , Cupples L. Adrienne , Rifai Nader , White Charles , Wang Thomas J. , Gardner Jeffrey P. , Cao Xiaogian , Benjamin Emelia J. , Levy Daniel , Aviv Abraham
Published: February 2008

Background—

Leukocyte telomere length (LTL) chronicles the cumulative burden of oxidative stress and inflammation over a life course. Activation of the renin-angiotensin-aldosterone system is associated with increased oxidative stress and inflammation. Therefore, LTL may be related to circulating biomarkers of the renin-angiotensin-aldosterone system.

Methods and Results—

We evaluated the cross-sectional relations of LTL (dependent variable) to circulating renin and aldosterone concentrations and the renin-to-aldosterone ratio (all logarithmically transformed; independent variables) in 1203 Framingham Study participants (mean age, 59 years; 51% women). We used multivariable linear regression and adjusted for age, blood pressure, hypertension treatment, smoking, diabetes mellitus, body mass index, hormone replacement therapy, serum creatinine, and the urine sodium-to-creatinine ratio. Overall, multivariable-adjusted LTL was inversely related to renin (β coefficient per unit increase, −0.038;
P
=0.036), directly related to aldosterone (β=0.099;
P
=0.002), and inversely related to the renin-to-aldosterone ratio (β=−0.049;
P
=0.003). Relations of LTL to biomarkers were stronger in those with hypertension, although a formal test of interaction was not statistically significant (
P
=0.20). Individuals with hypertension displayed significant associations of LTL with renin (β=−0.060;
P
=0.005), aldosterone (β=0.134;
P
=0.002), and renin-to-aldosterone ratio (β=−0.072;
P
<0.001). Participants with hypertension who were in the top tertile of the renin-to-aldosterone ratio had LTL that was 182 base pairs shorter relative to those in the lowest tertile.

Conclusions—

In our community-based sample, LTL was shorter in individuals with a higher renin-to-aldosterone ratio, especially in participants with hypertension. Additional investigations are warranted to confirm our observations.
Optimal Medical Therapy With or Without Percutaneous Coronary Intervention to Reduce Ischemic Burden
Authors: Shaw Leslee J. , Berman Daniel S. , Maron David J. , Mancini G. B. John , Hayes Sean W. , Hartigan Pamela M. , Weintraub William S. , O’Rourke Robert A. , Dada Marcin , Spertus John A. , Chaitman Bernard R. , Friedman John , Slomka Piotr , Heller Gary V. , Germano Guido , Gosselin Gilbert , Berger Peter , Kostuk William J. , Schwartz Ronald G. , Knudtson Merill , Veledar Emir , Bates Eric R. , McCallister Benjamin , Teo Koon K. , Boden William E.
Published: February 2008

Background—

Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS).

Methods and Results—

Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374±50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered ≥10% myocardium. The primary end point was ≥5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (−2.7%; 95% confidence interval, −1.7%, −3.8%) than with OMT (−0.5%; 95% confidence interval, −1.6%, 0.6%;
P
<0.0001). More PCI+OMT patients exhibited significant ischemia reduction (33% versus 19%;
P
=0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%;
P
=0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction (
P
=0.037 [risk-adjusted
P
=0.26]), particularly if baseline ischemia was moderate to severe (
P
=0.001 [risk-adjusted
P
=0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to ≥10% residual ischemia on follow-up MPS (
P
=0.002 [risk-adjusted
P
=0.09]).

Conclusions—

In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of ≥5% ischemia reduction with OMT with or without coronary revascularization.
Endothelium-Specific GTP Cyclohydrolase I Overexpression Attenuates Blood Pressure Progression in Salt-Sensitive Low-Renin Hypertension
Authors: Du Yan-Hua , Guan Yong-Yuan , Alp Nicholas J. , Channon Keith M. , Chen Alex F.
Published: February 2008

Background—

Tetrahydrobiopterin (BH4) is an essential cofactor of endothelial nitric oxide synthase (eNOS). When BH4 levels are decreased, eNOS becomes uncoupled to produce superoxide anion (O
2
−
) instead of NO, which contributes to endothelial dysfunction. Deoxycorticosterone acetate (DOCA)–salt hypertension is characterized by a suppressed plasma renin level due to sodium retention but manifests in eNOS uncoupling; however, how endogenous BH4 regulates blood pressure is unknown. GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for de novo BH4 synthesis. This study tested the hypothesis that endothelium-specific GTPCH I overexpression retards the progression of hypertension through preservation of the structure and function of resistance mesenteric arteries.

Methods and Results—

During 3 weeks of DOCA-salt treatment, arterial blood pressure was increased significantly in wild-type mice, as determined by radiotelemetry, but this increase was attenuated in transgenic mice with endothelium-specific GTPCH I overexpression (Tg-GCH). Arterial GTPCH I activity and BH4 levels were decreased significantly in wild-type DOCA-salt mice, but both were preserved in Tg-GCH mice despite DOCA-salt treatment. Significant remodeling of resistance mesenteric arteries (≈100-μm outside diameter) in wild-type DOCA-salt mice exists, evidenced by increased medial cross-sectional area, media thickness, and media-lumen ratio and overexpression of tenascin C, an extracellular matrix glycoprotein that contributes to hypertrophic remodeling; all of these effects were prevented in DOCA-salt–treated Tg-GCH mice. Furthermore, NO-mediated relaxation in mesenteric arteries was significantly improved in DOCA-salt–treated Tg-GCH mice, in parallel with reduced O
2
−
levels. Finally, phosphorylation of eNOS at serine residue 1177 (eNOS-S
1177
), but not its dimer-monomer ratio, was decreased significantly in wild-type DOCA-salt mice compared with sham controls but was preserved in DOCA-salt–treated Tg-GCH mice.

Conclusions—

These results demonstrate that endothelium-specific GTPCH I overexpression abrogates O
2
−
production and preserves eNOS phosphorylation, which results in preserved structural and functional integrity of resistance mesenteric arteries and lowered blood pressure in low-renin hypertension.
Cardioprotective Function of the Long Pentraxin PTX3 in Acute Myocardial Infarction
Authors: Salio Monica , Chimenti Stefano , De Angelis Noeleen , Molla Fabiola , Maina Virginia , Nebuloni Manuela , Pasqualini Fabio , Latini Roberto , Garlanda Cecilia , Mantovani Alberto
Published: February 2008

Background—

Despite widespread clinical use as a prognostic marker in ischemic heart disorders, the actual pathogenetic role of the short pentraxin, C-reactive protein, has not undergone stringent genetic testing because of evolutionary divergence between mouse and humans. The long pentraxin PTX3 is conserved in evolution, is expressed in the heart under inflammatory conditions, and is a candidate prognostic marker in acute myocardial infarction. It was therefore important to assess whether PTX3 plays a pathogenetic role in acute myocardial infarction.

Methods and Results—

In a model of acute myocardial infarction caused by coronary artery ligation and reperfusion, tissue mRNA expression and circulating levels of PTX3 increased. The interleukin-1R–MyD88 pathway plays a pivotal role in the induction of PTX3 transcript after ischemia.
ptx3
-deficient mice showed exacerbated heart damage (33% larger infarcts in null mice;
P
=0.0047). Increased myocardial damage in
ptx3
-deficient mice was associated with a greater no-reflow area, increased neutrophil infiltration, decreased number of capillaries, and increased number of apoptotic cardiomyocytes. In addition,
ptx3
-deficient mice with acute myocardial infarction showed higher circulating levels of interleukin-6 and increased C3 deposition in lesional tissue. The phenotype was reversed by exogenous PTX3.

Conclusions—

Thus, PTX3 plays a nonredundant, regulatory, cardioprotective role in acute myocardial infarction in mice. Our results suggest that modulation of the complement cascade contributes to the cardioprotective function of PTX3.
Activatable Magnetic Resonance Imaging Agent Reports Myeloperoxidase Activity in Healing Infarcts and Noninvasively Detects the Antiinflammatory Effects of Atorvastatin on Ischemia-Reperfusion Injury
Authors: Nahrendorf Matthias , Sosnovik David , Chen John W. , Panizzi Peter , Figueiredo Jose-Luiz , Aikawa Elena , Libby Peter , Swirski Filip K. , Weissleder Ralph
Published: February 2008

Background—

Ischemic injury of the myocardium causes timed recruitment of neutrophils and monocytes/macrophages, which produce substantial amounts of local myeloperoxidase (MPO). MPO forms reactive chlorinating species capable of inflicting oxidative stress and altering protein function by covalent modification. We have used a small-molecule, gadolinium-based activatable sensor for magnetic resonance imaging of MPO activity (MPO-Gd). MPO-Gd is first radicalized by MPO and then either spontaneously oligomerizes or binds to matrix proteins, all leading to enhanced spin-lattice relaxivity and delayed washout kinetics. We hypothesized that MPO imaging could be used to measure inflammatory responses after myocardial ischemia locally and noninvasively in a murine model.

Methods and Results—

We injected 0.3 mmol/kg MPO-Gd (or Gd-DTPA as control) and performed magnetic resonance imaging up to 120 minutes later in mice 2 days after myocardial infarction. The contrast-to-noise ratio (infarct versus septum) after Gd-DTPA injection peaked at 10 minutes and returned to preinjection values at 60 minutes. After injection of MPO-Gd, the contrast-to-noise ratio peaked later and was higher than Gd-DTPA (40.8±10.4 versus 10.5±0.2;
P
<0.05). MPO imaging was validated by magnetic resonance imaging of MPO
−/−
mice and correlated well with immunoreactive staining (
r
2
=0.92,
P
<0.05), tissue activity by guaiacol assay (
r
2
=0.65,
P
<0.001), and immunoblotting. In time course imaging, activity peaked 2 days after coronary ligation. Flow cytometry of digested infarcts detected MPO in neutrophils and monocytes/macrophages. Furthermore, serial MPO imaging accurately tracked the antiinflammatory effects of atorvastatin therapy after ischemia-reperfusion injury.

Conclusions—

MPO-Gd enables in vivo assessment of MPO activity in injured myocardium. This approach allows noninvasive evaluation of the inflammatory response to ischemia and has the potential to guide the development of novel cardioprotective therapies.
Prevalence, Awareness, Treatment, and Control of Hypertension in the Jackson Heart Study
Authors: Wyatt Sharon B. , Akylbekova Ermeg L. , Wofford Marion R. , Coady Sean A. , Walker Evelyn R. , Andrew Michael E. , Keahey Wanda J. , Taylor Herman A. , Jones Daniel W.
Published: February 2008

African Americans have higher reported hypertension prevalence and lower control rates than other ethnic groups in the United States. Hypertension prevalence, awareness, treatment, and control (outcomes) and potentially associated demographic, lifestyle, comorbidity, and health care access factors were examined in 5249 adult participants (3362 women and 1887 men) aged 21 to 94 years enrolled in the Jackson Heart Study. Hypertension prevalence (62.9%), awareness (87.3%), treatment (83.2%), and control (66.4%) were high. Control declined with advancing age; estimates for all of the outcomes were higher for women compared with men. Lower socioeconomic status was associated with prevalence and control. Smoking was negatively associated with awareness and treatment, particularly among men. Comorbidities (diabetes, chronic kidney disease, and cardiovascular disease), likely driven by the high rates of obesity, correlated with hypertension prevalence, awareness, treatment, and control. Lack of health insurance was marginally associated with poorer control, whereas use of preventive care was positively associated with prevalence, awareness, and treatment, particularly among men. In comparisons with the 1994–2004 National Health and Nutrition Examination Survey data adjusted to Jackson Heart Study sex, age, and socioeconomic status distribution, control rates among Jackson Heart Study participants appeared to be higher than in their national counterparts and similar to that of whites. These results suggest that public health efforts to increase awareness and treatment among African Americans have been relatively effective. The Jackson Heart Study data indicate that better control rates can be achieved in this high-risk population.
Pulsatile but Not Steady Component of Blood Pressure Predicts Cardiovascular Events in Coronary Patients
Authors: Jankowski Piotr , Kawecka-Jaszcz Kalina , Czarnecka Danuta , Brzozowska-Kiszka Małgorzata , Styczkiewicz Katarzyna , Loster Magdalena , Kloch-Badełek Małgorzata , Wiliński Jerzy , Curyło Adam M. , Dudek Dariusz
Published: February 2008

Although the differences between central and peripheral blood pressure (BP) values have been known for decades, the consequences of decision making based on peripheral rather than central BP have only recently been recognized. There are only a few studies assessing the relationship between intraaortic BP and cardiovascular risk. In addition, the relationship between central BP and the risk of cardiovascular events in a large group of coronary patients has not yet been evaluated. Therefore, the aim of the study was to determine the prognostic significance of central BP-derived indices in patients undergoing coronary angiography. Invasive central BPs were taken at baseline, and study end points were ascertained during over a 4.5-year follow-up in 1109 consecutive patients. The primary end point (cardiovascular death or myocardial infarction or stroke or cardiac arrest or heart transplantation or myocardial revascularization) occurred in 246 (22.2%) patients. Central pulsatility was the most powerful predictor of the primary end point (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.14 to 1.48). Central pulse pressure was also independently related to the primary end point (HR 1.25, 95% CI 1.09 to 1.43). Central mean BP as well as peripheral BP parameters were not independently related to the primary end point risk. Central pulsatility was also related to risk of cardiovascular death or myocardial infarction or stroke. The pulsatile component of BP is the most important factor related to the cardiovascular risk in coronary patients. It is more closely associated with cardiovascular risk than steady component of BP.
Expression, Transcription, and Possible Antagonistic Interaction of the Human
Nedd4L
Gene Variant
Authors: Araki Naomi , Umemura Masanari , Miyagi Yohei , Yabana Machiko , Miki Yuko , Tamura Koichi , Uchino Kazuaki , Aoki Reina , Goshima Yoshio , Umemura Satoshi , Ishigami Tomoaki
Published: February 2008

Net sodium balances in humans are maintained through various ion transporters expressed along the entire nephron. Among these ion transporters, epithelial sodium channels (ENaC) located along the aldosterone-sensitive distal nephron (ASDN) play a pivotal role in the homeostasis of sodium balance. This is supported by analyses of inherited hypertensive disorders, showing that genes encoding ENaC and other modulatory proteins cause hereditary hypertension, such as Liddle syndrome. Among various modulating proteins, E3 ubiquitin ligase, Nedd4L, binds the PY motif of ENaC COOH terminals and catalyzes ubiquitination of the NH
2
terminus of the protein for subsequent degradation. Both evolutionarily conserved and evolutionarily new C2 domains of human Nedd4L, a cryptic splice variant resulting in a disrupted isoform product formed by a frame-shift mutation, were reported previously. We focused on one of the isoforms, isoform I, generated by SNP (rs4149601), and studied its expression and interactions with other isoforms by molecular biological, immunohistochemical, and electrophysiological methods. We found that isoform I may interact with other human isoforms in a dominant-negative fashion. Such interactions might abnormally increase sodium reabsorption. Taken together, our analyses suggest that the human
Nedd4L
gene, especially the evolutionarily new isoform I, is a candidate gene for hypertension.