bluuebunny/crossref_metadata_2025 huggingface dataset:
MODULUS OF CORE REACTION APPROACH TO BUCKLING OF SANDWICH PLATES
Authors: JAYACHANDRAN S. ARUL , SOUNDARARAJAN A. , SEETHARAMAN S. , KNIGHT G. M. SAMUEL
Published: November 2004

This paper deals with the linear stability analysis of sandwich plates modeled as thin plates resting on elastic media. To compute the elastic buckling coefficient of sandwich plates, equations have been presented in the literature by using a coefficient R, which relates the rigidity of facing to the core. In the finite element analysis, if the sandwich plates are to be modeled as plates supported by Winkler elastic springs, the relative rigidity R cannot be directly used to represent the stiffness of the Winkler springs. Instead, the stiffness of the core has to be expressed as a modulus of subgrade/core reaction. Furthermore, the R value cannot be directly used in a finite element postbuckling analysis of sandwich plates. In this study, an empirical relation between modulus of core reaction and the R value is established. This is then used in the finite element computation of buckling loads of sandwich panels. This modulus of core reaction can be directly used in the linear buckling analysis of sandwich plates as well as the postbuckling analysis using finite elements.
Factors Affecting IT-Based Knowledge Management Strategy in UK Healthcare System
Authors: Guah Matthew W. , Currie Wendy L.
Published: November 2004

The technological development by the beginning of the 21st century is making it humanly impossible for unaided healthcare professionals to possess all the knowledge needed to deliver medical care with the efficacy and safety made possible by current scientific knowledge. Several healthcare organizations are adopting rigorous methods and technologies for KM as a potential solution to the knowledge predicament. However, awareness and understanding of such methods are not widespread with critics claiming that these technologies are not designed to be compatible with others neither are they interoperable.

This paper describes an effort by the NHS for individuals, organizations and partners (commercial companies supplying services to the NHS) to demonstrate their belief in the importance of improving KM in medicine and show that this can be best achieved through collaboration and consensus. It looks at National Knowledge Service, set up to provide a range of services, through one or more open-access web sites.

There is an asymmetry in most of the discussion of the field. KM, in this paper, is primarily discussed from the point of view of the user of medical knowledge. The motivation is seen to be the enhancement capabilities, and the utilization of knowledge to increase healthcare effectiveness.
The Impact of Knowledge Management Technology on Intellectual Capital
Authors: O'Sullivan Kevin J. , Stankosky Michael
Published: November 2004

As we have moved into the knowledge economy, many organizations have invested in knowledge management initiatives. A great deal of the focus of these initiatives has been on the technological aspects of knowledge management with many organizations implementing knowledge management systems utilizing various technologies. As these technologies have moved to common use in these organizations, there has been the opportunity to use them to manage more than pure knowledge.

The purpose of this research is to determine the extent to which knowledge management technologies are being used to manage intellectual capital. It identifies eight main groupings of knowledge management technologies that are examined in the context of the core elements of intellectual capital — human capital, customer capital and relationship capital. Based on the type of technology used, the research examines whether it is more or less likely to succeed in managing the different elements of intellectual capital. In the case of all three areas of intellectual capital we show that knowledge management technologies are used successfully.

The results of the research illustrate which technologies are more effective in managing intellectual capital taking organizational size into consideration. It adds to the growing body of knowledge by illustrating the value of knowledge management initiatives beyond the scope of the predominant perception of how knowledge management tools are used.
Knowledge Management Styles and Organizational Performance: An Empirical Study in a K-Space Framework
Authors: Al-Hawari Maen , Hasan Helen
Published: November 2004

This paper addresses the relationships between certain attributes of knowledge, knowledge management styles and organizational performance. From an extensive study of the literature, an innovative knowledge space (K-Space) model of organizational knowledge was developed as the first stage of the research. This led to the identification of four knowledge management styles and a framework that relates these styles to knowledge creation and improved organizational performance. A survey instrument was developed to measure the constructs contributing to the relationships in this framework and mailed to 338 organizations in different Australian industries. The results confirm that an organization can improve its performance through better management of its knowledge capabilities. Using a MANOVA analysis, the four knowledge management styles were found to be deployed in significantly different ways by organizations in different industry types. There is, however, in all organizations a particular benefit from deploying a balance of knowledge management styles which combine the human and technology perspectives. The findings of the study also demonstrate that the K-Space model provides a basis for a new way of conceptualising knowledge creation processes within organizations.
Knowledge Creation in Export Trading
Authors: Soon Lisa , Chen Yi-Ping Phoebe , Underwood Alan
Published: November 2004

In this research, we investigate how knowledge in the export trading industry is created. Prior research focuses on general businesses in local market environment. This research specifically focuses on export trading with overseas market needs. These needs require attention to different types of control and requirements beyond that of a local market. In this paper, Nonaka et al.'s theory of organizational knowledge creation is explored. We specifically examine the processes of knowledge creation through four modes of knowledge conversion. Empirical investigations in export trading organizations are conducted. We examine how export firms obtain new knowledge for innovations based on collective knowledge being used in export trading. The findings indicate that the knowledge management processes in export firms allow for the creation of new knowledge. The collective knowledge (from groups and individuals) forms a basis for innovations and competitive intelligence. This collective knowledge also creates foresight, insight and hindsight in the export trading context.
ρ-DIFFERENTIAL CALCULI AND LINEAR CONNECTIONS ON MATRIX ALGEBRA
Authors: CIUPALĂ CĂTĂLIN
Published: November 2004

In this paper we present a new aproach of the noncommutative geometry of the matrix algebra [Formula: see text]. We define two different differential calculi, and we introduce linear connections on [Formula: see text] using the framewok of ρ-algebras.
THE NUCLEAR STRUCTURE OF HEAVY-ACTINIDE AND TRANS ACTINIDE NUCLEI
Authors: Leino M. , Heßberger F.P.
Published: November 2004

▪ Abstract  One can extract unique information about the nuclear interaction from the study of the heaviest elements. They exist solely on the basis of quantum effects, which create a barrier against spontaneous fission. The important questions concern the end of the periodic table and the location of the next closed nucleon shells. Considerable progress was achieved during the past few years in structure studies in this region. This was made possible by the development of detector systems for decay and in-beam studies using recoil separators and heavy ion fusion reactions. We concentrate on these developments and on recent results from structure studies in the region from einsteinium to dubnium. We present recent data on the elements 110 (darmstadtium), 111, and 112, and discuss claims for the synthesis of even heavier elements. We discuss the implications of these studies for predicting the location of the next spherical shells and give a brief outlook on the future.
ELECTROMAGNETIC FORM FACTORS OF THE NUCLEON AND COMPTON SCATTERING
Authors: Hyde-Wright Charles Earl , de Jager Kees
Published: November 2004

▪ Abstract  We review the experimental and theoretical status of elastic electron scattering and elastic low-energy photon scattering (with both real and virtual photons) from the nucleon. As a consequence of new experimental facilities and new theoretical insights, these subjects are advancing with unprecedented precision. These reactions provide many important insights into the spatial distributions and correlations of quarks in the nucleon.
THE BROOKHAVEN MUON ANOMALOUS MAGNETIC MOMENT EXPERIMENT
Authors: Hertzog David W. , Morse William M.
Published: November 2004

▪ Abstract  The E821 Experiment at the Brookhaven Alternating Gradient Synchrotron has measured the muon anomalous magnetic moment aμ to a relative precision of 0.5 parts per million. This effort required a new beamline, a super-ferric muon storage ring with a highly uniform magnetic field, a precision magnetic field measurement system, and electromagnetic calorimeters to record the electrons from muon decay, which carry the essential spin precession frequency information. Data obtained over five years resulted in more than nine billion analyzed events, in nearly equal samples of both muon charges. The experimental results [Formula: see text] and [Formula: see text] are consistent with each other, as predicted by the CPT invariance theorem. The combined result aμ ± = 11 659 208(6) × 10−10 is 0.9–2.4 standard deviations higher than predicted by theory; the range depends on the method employed to obtain the hadronic vacuum polarization term in the standard-model calculation. We review the experimental design, physical realization, and analysis procedures and compare the results to the theoretical prediction.
THE GERASIMOV-DRELL-HEARN SUM RULE AND THE SPIN STRUCTURE OF THE NUCLEON
Authors: Drechsel Dieter , Tiator Lothar
Published: November 2004

▪ Abstract  The Gerasimov-Drell-Hearn sum rule is one of several dispersive sum rules that connect the Compton scattering amplitudes to the inclusive photoproduction cross sections of the target under investigation. Being based on such universal principles as causality, unitarity, and gauge invariance, these sum rules provide a unique testing ground to study the internal degrees of freedom that hold the system together. The present article reviews these sum rules for the spin-dependent cross sections of the nucleon by presenting an overview of recent experiments and theoretical approaches. The generalization from real to virtual photons provides a microscope of variable resolution: At small virtuality of the photon, the data sample information about the long-range phenomena, which are described by effective degrees of freedom (Goldstone bosons and collective resonances), whereas the primary degrees of freedom (quarks and gluons) become visible at the larger virtualities. Through a rich body of new data and several theoretical developments, a unified picture of virtual Compton scattering emerges, which ranges from coherent to incoherent processes, and from the generalized spin polarizabilities on the low-energy side to higher twist effects in deep-inelastic lepton scattering.
THE THEORETICAL PREDICTION FOR THE MUON ANOMALOUS MAGNETIC MOMENT
Authors: Davier Michel , Marciano William J.
Published: November 2004

▪ Abstract  This article reviews the standard-model prediction for the anomalous magnetic moment of the muon and describes recent updates of QED, electroweak, and hadronic contributions. Comparison of theory and experiment suggests a 2.4 σ difference if [Formula: see text] hadrons data are used to evaluate the main hadronic effects, but a smaller discrepancy if hadronic τ decay data are employed. Implications of a deviation for “new physics” contributions, along with an outlook for future improvements in theory and experiment, are briefly discussed.
THE SOLARhepPROCESS
Authors: Kubodera Kuniharu , Park Tae-Sun
Published: November 2004

▪ Abstract  The hep process is a weak-interaction reaction, [Formula: see text], which occurs in the sun. There is renewed interest in hep owing to current experimental efforts to extract from the observed solar neutrino spectrum information on nonstandard physics in the neutrino sector. hep produces highest-energy solar neutrinos, although their flux is quite modest. This implies that the hep neutrinos can at some level influence the solar neutrino spectrum near its upper end. Therefore, a precise interpretation of the observed solar neutrino spectrum requires an accurate estimate of the hep rate. This is an interesting but challenging task. We describe the difficulties involved and how the recent theoretical developments in nuclear physics have enabled us to largely overcome these difficulties. A historical survey of hep calculations is followed by an overview of the latest developments. We compare the results obtained in the conventional nuclear physics approach and those obtained in a newly developed effective field theory approach. We also discuss the current status of the experiments relevant to hep.
GRAVITATIONAL WAVE ASTRONOMY
Authors: Camp Jordan B. , Cornish Neil J.
Published: November 2004

▪ Abstract  The existence of gravitational radiation is a direct prediction of Einstein's theory of general relativity, published in 1916. The observation of gravitational radiation will open a new astronomical window on the universe, allowing the study of dynamic strong-field gravity, as well as many other astrophysical objects and processes impossible to observe with electromagnetic radiation. The relative weakness of the gravitational force makes detection extremely challenging; nevertheless, sustained advances in detection technology have made the observation of gravitational radiation probable in the near future. In this article, we review the theoretical and experimental status of this emerging field.
Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes
Authors: Ravikumar B. , Carey P. E. , Snaar J. E. M. , Deelchand D. K. , Cook D. B. , Neely R. D. G. , English P. T. , Firbank M. J. , Morris P. G. , Taylor R.
Published: November 2004

Liver and skeletal muscle triglyceride stores are elevated in type 2 diabetes and correlate with insulin resistance. As postprandial handling of dietary fat may be a critical determinant of tissue triglyceride levels, we quantified postprandial fat storage in normal and type 2 diabetes subjects. Healthy volunteers ( n = 8) and diet-controlled type 2 diabetes subjects ( n = 12) were studied using a novel 13C magnetic resonance spectroscopy protocol to measure the postprandial increment in liver and skeletal muscle triglyceride following ingestion of 13C-labeled fatty acids given with a standard mixed meal. The postprandial increment in hepatic triglyceride was rapid in both groups (peak increment controls: +7.3 ± 1.5 mmol/l at 6 h, P = 0.002; peak increment diabetics: +10.8 ± 3.4 mmol/l at 4 h, P = 0.009). The mean postprandial incremental AUC of hepatic 13C enrichment between the first and second meals (0 and 4 h) was significantly higher in the diabetes group (6.1 ± 1.4 vs. 1.7 ± 0.6 mmol·l−1·h−1, P = 0.019). Postprandial increment in skeletal muscle triglyceride in the control group was small compared with the diabetic group, the mean 24-h postprandial incremental AUC being 0.2 ± 0.3 vs. 1.7 ± 0.4 mmol·l−1·h−1 ( P = 0.009). We conclude that the postprandial uptake of fatty acids by liver and skeletal muscle is increased in type 2 diabetes and may underlie the elevated tissue triglyceride stores and consequent insulin resistance.
Fixed point characterization of left amenable Lau algebras
Authors: Nasr-Isfahani R.
Published: November 2004

The present paper deals with the concept of left amenability for a wide range of Banach algebras known as Lau algebras. It gives a fixed point property characterizing left amenable Lau algebras 𝒜
in terms of left Banach 𝒜‐modules. It also offers an application of this result to some Lau algebras related to a locally compact group G, such as the Eymard‐Fourier algebra A(G), the Fourier‐Stieltjes algebra B(G), the group algebra L1(G), and the measure algebra M(G). In particular, it presents some equivalent statements which characterize amenability of locally compact groups.
Magnetohydrodynamics effect on three‐dimensional viscous incompressible flowbetween two horizontal parallel porous plates and heat transfer withperiodic injection/suction
Authors: Sharma Pawan Kumar , Chaudhary R. C.
Published: November 2004

We investigate the hydromagnetic effect on viscous incompressible flow between two horizontal parallel porous flat plates with transverse sinusoidal injection of the fluid at the stationary plate and its corresponding removal by periodic suction through the plate in uniform motion. The flow becomes three dimensional
due to this injection/suction velocity. Approximate solutions are obtained for the flow field, the pressure, the skin‐friction, the temperature field, and the rate of heat transfer. The dependence of solution on M
(Hartmann number) and λ
(injection/suction) is investigated by the graphs and tables.
Linear maps preserving rank 2 on the space of alternatematrices and their applications
Authors: Cao Chongguang , Tang Xiaomin
Published: November 2004

Denote by 𝒦n(F) the linear space of all
n × n
alternate matrices over a field F. We first characterize all linear bijective maps on 𝒦n(F)(n ≥ 4) preserving rank 2 when F is any field, and thereby the characterization of all linear bijective maps on 𝒦n(F) preserving the max‐rank is done when F is any field
except for {0, 1}
. Furthermore, the linear preservers of the determinant (resp., adjoint) on
𝒦n(F) are also characterized by
reducing them to the linear preservers of the max‐rank when n
is even and F
is any field except for {0, 1}. This paper can be viewed as a supplement version of several related results.
Controlling the dynamics of Burgers equation with a high‐order nonlinearity
Authors: Smaoui Nejib
Published: November 2004

We investigate analytically as well as numerically Burgers equation with a high‐order nonlinearity (i.e.,
ut = νuxx − unux + mu + h(x)). We show existence of an absorbing ball in L2[0, 1]
and uniqueness of steady state solutions for all integer n ≥ 1. Then, we use an adaptive nonlinear boundary controller to show that it guarantees global asymptotic stability in time and convergence of the solution to the trivial solution. Numerical results using Chebychev collocation method with backward Euler time stepping scheme are presented for both the controlled and the uncontrolled equations illustrating the performance of the controller and supporting the analytical results.
On the optimality of double‐bracket flows
Authors: Bloch Anthony M. , Iserles Arieh
Published: November 2004

We analyze the optimality of the stable fixed point of the double‐bracket equations. We introduce different types of optimality and prove local and global optimality results with respect to the
Schatten p‐norms.
Tissue Factor–Factor VIIa Signaling
Authors: Rao L. Vijaya Mohan , Pendurthi Usha R.
Published: November 2004

How does tissue factor (TF), whose principle role is to support clotting factor VIIa (FVIIa) in triggering the coagulation cascade, affect various pathophysiological processes? One of the answers is that TF interaction with FVIIa not only initiates clotting but also induces cell signaling via activation of G-protein–coupled protease activated receptors (PARs). Recent studies using various cell model systems and limited in vivo systems are beginning to define how TF–VIIa-induced signaling regulates cellular behavior. Signaling pathways initiated by both TF–VIIa protease activation of PARs and phosphorylation of the TF–cytoplasmic domain appear to regulate cellular functions. In the present article, we review the emerging data on the mechanism of TF-mediated cell signaling and how it regulates various cellular responses, with particular focus on TF–VIIa protease-dependent signaling.
Statins and Blood Coagulation
Authors: Undas Anetta , Brummel-Ziedins Kathleen E. , Mann Kenneth G.
Published: November 2004

The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events.
Inhibition of Triglyceride Synthesis as a Treatment Strategy for Obesity
Authors: Chen Hubert C. , Farese Robert V.
Published: November 2004

Because the ability to make triglycerides is essential for the accumulation of adipose tissue, inhibition of triglyceride synthesis may ameliorate obesity and its related medical consequences. Acyl coenzyme A (CoA):diacylglycerol acyltransferase 1 (DGAT1) is 1 of 2 DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 are resistant to obesity and have increased sensitivity to insulin and leptin. DGAT1-deficient mice are also resistant to diet-induced hepatic steatosis. The effects of DGAT1 deficiency on energy and glucose metabolism result in part from the altered secretion of adipocyte-derived factors. Although complete DGAT1 deficiency causes alopecia and impairs development of the mammary gland, these abnormalities are not observed in mice with partial DGAT1 deficiency. These findings suggest that pharmacological inhibition of DGAT1 may be a feasible therapeutic strategy for human obesity and type 2 diabetes.
Effects of Exercise Training and Deconditioning on Platelet Aggregation Induced by Alternating Shear Stress in Men
Authors: Wang Jong-Shyan , Li Yu-San , Chen Jin-Chung , Chen Yu-Wen
Published: November 2004

Objective—

Alternating shear stress, which resembles the flow condition in stenotic arteries, induces platelet aggregation. This study investigated how exercise training and deconditioning influence alternating shear-induced platelet aggregation (ASIPA) and clarify the mechanisms underlying ASIPA.

Methods and Results—

Thirty healthy male sedentary subjects were randomly divided into control and trained groups. The trained men were trained on a bicycle ergometer at ≈60% of maximal oxygen consumption for 30 minutes per day, 5 days per week for 8 weeks, and then were deconditioned for 8 weeks. The experimental results indicate the following: (1) short-term strenuous exercise increases the extent of ASIPA and is accompanied by increased the von Willebrand factor (vWF) binding and P-selectin expression on platelets in both the control and trained groups, whereas the enhancement of platelet function decreases after exercise training in trained subjects; (2) at rest and immediately after exercise, ASIPA and the vWF binding and P-selectin expression on platelets are reduced by training, but remain unchanged in the control group; and (3) deconditioning reverses the effects of training on resting and postexercise state.

Conclusions—

Exercise training suppresses the extent of ASIPA, probably by reducing vWF binding to platelets and P-selectin expression on platelets. However, deconditioning reverses the training effects.
Thrombin Stimulates Human Endothelial Arginase Enzymatic Activity via RhoA/ROCK Pathway
Authors: Ming Xiu-Fen , Barandier Christine , Viswambharan Hema , Kwak Brenda R. , Mach François , Mazzolai Lucia , Hayoz Daniel , Ruffieux Jean , Rusconi Sandro , Montani Jean-Pierre , Yang Zhihong
Published: November 2004

Background—

Arginase competes with endothelial nitric oxide synthase (eNOS) for the substrate
l
-arginine and decreases NO production. This study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis.

Methods and Results—

In human endothelial cells isolated from umbilical veins, thrombin concentration- and time-dependently stimulated arginase enzymatic activity, reaching a 1.9-fold increase (
P
<0.001) at 1 U/mL for 24 hours. The effect of thrombin was prevented by C3 exoenzyme or the HMG-CoA reductase inhibitor fluvastatin, which inhibit RhoA, or by the ROCK inhibitors Y-27632 and HA-1077. Adenoviral expression of constitutively active RhoA or ROCK mutants enhanced arginase activity (≈3-fold,
P
<0.001), and the effect of active RhoA mutant was inhibited by the ROCK inhibitors. Neither thrombin nor the active RhoA/ROCK mutants affected arginase II protein level, the only isozyme detectable in the cells. Moreover, a significantly higher arginase II activity (1.5-fold, not the protein level) and RhoA protein level (4-fold) were observed in atherosclerotic aortas of apoE
−/−
compared with wild-type mice. Interestingly,
l
-arginine (1 mmol/L), despite a significantly higher eNOS expression in aortas of apoE
−/−
mice, evoked a more pronounced contraction, which was reverted to a greater vasodilation by the arginase inhibitor
l
-norvaline (20 mmol/L) compared with the wild-type animals (n=5,
P
<0.001).

Conclusions—

Thrombin enhances arginase activity via RhoA/ROCK in human endothelial cells. Higher arginase enzymatic activity is involved in atherosclerotic endothelial dysfunction in apoE
−/−
mice. Targeting vascular arginase may represent a novel therapeutic possibility for atherosclerosis.
Toll-Like Receptor 2 Mediates
Staphylococcus aureus
–Induced Myocardial Dysfunction and Cytokine Production in the Heart
Authors: Knuefermann Pascal , Sakata Yasushi , Baker J. Scott , Huang Chien-Hua , Sekiguchi Kenichi , Hardarson Hordur S. , Takeuchi Osamu , Akira Shizuo , Vallejo Jesus G.
Published: November 2004

Background—

Staphylococcus aureus
sepsis is associated with significant myocardial dysfunction. Toll-like receptor 2 (TLR2) mediates the inflammatory response to
S aureus
and may trigger an innate immune response in the heart. We hypothesized that a TLR2 deficiency would attenuate
S aureus
–induced cardiac proinflammatory mediator production and the development of cardiac dysfunction.

Methods and Results—

Wild-type and TLR2-deficient (TLR2D) mice were studied.
S aureus
challenge significantly increased tumor necrosis factor, interleukin-1β, and nitric oxide expression in hearts of wild-type mice. This response was significantly blunted in TLR2D mice. Hearts from TLR2D mice had impaired
S aureus
–induced activation of interleukin-1 receptor–associated kinase, c-Jun NH
2
terminal kinase, nuclear factor-κB, and activator protein-1. Moreover, hearts from TLR2D mice were protected against
S aureus
–induced contractile dysfunction.

Conclusions—

These results show for the first time that TLR2 signaling contributes to the loss of myocardial contractility and cytokine production in the heart during
S aureus
sepsis.
Factor V
Leiden
Inhibits Fibrinolysis In Vivo
Authors: Parker Andrew C. , Mundada Lakshmi V. , Schmaier Alvin H. , Fay William P.
Published: November 2004

Background—

Factor V
Leiden
(fV
Leiden
) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fV
Leiden
inhibits fibrinolysis in vivo.

Methods and Results—

Radiolabeled clots were injected into the jugular veins of wild-type mice and mice heterozygous (
fV
+/Q
) or homozygous (
fV
Q/Q
) for fV
Leiden
. Mean percent clot lysis 5 hours later was significantly reduced in
fV
Q/Q
mice (14.3±3.6%, n=13) compared with wild-type mice (40.2±7.0%, n=17;
P
<0.01) and intermediate in
fV
+/Q
mice (29.4±8.7%, n=9;
P
<0.03 versus
fV
Q/Q
,
P
=0.36 versus wild type). The rate of in vitro lysis of plasma clots prepared from
fV
+/Q
or
fV
Q/Q
mice was significantly slower than that of wild-type plasma clots, whereas in vitro clot lysis did not differ significantly between groups after inhibiting thrombin-activatable fibrinolysis inhibitor.

Conclusions—

fV
Leiden
inhibits fibrinolysis in vivo, suggesting an additional pathway by which this mutation promotes thrombosis.
Postprandial Hypertriglyceridemia Increases Circulating Levels of Endothelial Cell Microparticles
Authors: Ferreira Alexandre C. , Peter Arley A. , Mendez Armando J. , Jimenez Joaquín J. , Mauro Lucia M. , Chirinos Julio A. , Ghany Reyan , Virani Salim , Garcia Santiago , Horstman Lawrence L. , Purow Joshua , Jy Wenche , Ahn Yeon S. , de Marchena Eduardo
Published: November 2004

Background—

This study evaluated a possible relationship between levels of endothelial microparticles (EMPs), known to be a sensitive indicator of endothelial disturbance, and changes in postprandial lipid levels in healthy volunteers after a low- or high-fat meal.

Methods and Results—

Eighteen healthy subjects without known cardiovascular risk factors were evaluated. Lipid and EMP levels were measured before and 1 and 3 hours after a single low- or high-fat isocaloric meal. The low-fat meal had no significant postprandial effect on EMPs or lipids compared with fasting levels. In contrast, a single high-fat meal significantly increased EMP levels after 1 and 3 hours, from 389±54 (thousands per milliliter) when fasting to 541±139 (
P
=0.0002) and 677±159 (
P
<0.0001), respectively, and correlated with a postprandial elevation in serum triglycerides.

Conclusions—

A single high-fat meal led to a significant elevation of plasma EMP levels in healthy, normolipidemic subjects and correlated with a postprandial elevation of serum triglycerides. EMPs may be an indirect marker of endothelial dysfunction or injury induced by postprandial triglyceride-rich lipoproteins.
Brachial Artery Vasodilator Function and Systemic Inflammation in the Framingham Offspring Study
Authors: Vita Joseph A. , Keaney John F. , Larson Martin G. , Keyes Michelle J. , Massaro Joseph M. , Lipinska Izabella , Lehman Birgitta T. , Fan Shuxia , Osypiuk Ewa , Wilson Peter W.F. , Vasan Ramachandran S. , Mitchell Gary F. , Benjamin Emelia J.
Published: November 2004

Background—

In experimental studies, traditional risk factors and proinflammatory processes alter the regulatory functions of the vascular endothelium to promote atherosclerosis. These alterations include expression of leukocyte adhesion molecules and decreased bioavailability of endothelium-derived nitric oxide, an important regulator of vascular homeostasis and tone. The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain.

Methods and Results—

To test the hypothesis that inflammation impairs endothelial function in humans, we measured brachial artery flow-mediated dilation, reactive hyperemia, and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), and monocyte chemotactic protein-1 (MCP-1) in 2701 participants from the Framingham Study (mean age 61 years, 53% women). There were modest unadjusted inverse correlations between flow-mediated dilation and CRP, IL-6, and sICAM-1 (
P
<0.001 for all) that were rendered nonsignificant after accounting for traditional coronary risk factors. For reactive hyperemia, we observed inverse correlations with markers of inflammation in unadjusted models that were attenuated 57% to 74% after accounting for risk factors. However, partial correlations of CRP, IL-6, and sICAM-1 with reactive hyperemia remained significant.

Conclusions—

Our observations are consistent with the hypothesis that risk factors induce a state of inflammation that impairs vascular function. For flow-mediated dilation, we found no evidence that inflammation has additional effects beyond those attributable to traditional risk factors. The incremental contribution of CRP, IL-6, and sICAM-1 to reactive hyperemia above and beyond known risk factors suggests that systemic inflammation may contribute to impaired vasomotor function in forearm microvessels.
Prenatal Environmental Tobacco Smoke Exposure Promotes Adult Atherogenesis and Mitochondrial Damage in Apolipoprotein E
−/−
Mice Fed a Chow Diet
Authors: Yang Zhen , Knight Cynthia A. , Mamerow Madonna M. , Vickers Kasey , Penn Arthur , Postlethwait Edward M. , Ballinger Scott W.
Published: November 2004

Background—

Environmental tobacco smoke (ETS) exposure is recognized as a cardiovascular disease risk factor; however, the impact of prenatal ETS exposure on adult atherogenesis has not been examined. We hypothesized that in utero ETS exposure promotes adult atherosclerotic lesion formation and mitochondrial damage.

Methods and Results—

Atherosclerotic lesion formation, mitochondrial DNA damage, antioxidant activity, and oxidant load were determined in cardiovascular tissues from adult apolipoprotein E
−/−
mice exposed to either filtered air or ETS in utero and fed a standard chow diet (4.5% fat) from weaning until euthanasia. All parameters were significantly altered in male mice exposed in utero to ETS.

Conclusions—

These data support the hypothesis that prenatal ETS exposure is sufficient to promote adult cardiovascular disease development.
Optimal Threshold Value for Left Ventricular Hypertrophy in Blacks
Authors: Nunez Eduardo , Arnett Donna K. , Benjamin Emelia J. , Liebson Philip R. , Skelton Thomas N. , Taylor Herman , Andrew Michael
Published: November 2004

The distribution of echocardiographic left ventricular (LV) mass differs among ethnicities. Because ethnic-specific echocardiographic criteria for LV hypertrophy (LVH) are not established, we determined whether threshold values derived from overwhelmingly white populations are appropriate for blacks, a subgroup having more LVH. Between 1992 and 1994, LV mass was measured echocardiographically in the Jackson, Mississippi, black cohort of the Atherosclerosis Risk in Communities study. Participants free of prevalent cardiovascular disease (CVD) (n=1616; mean±SD, age 59±5.7; 65% women and 57% with hypertension) were included. The optimal LVH threshold value was selected from the continuum of LV mass index (LVMI=LV mass/height
2.7
) using 3 methods: (1) the best operating point from the area under the resulting receiver-operating characteristic (ROC) curve predicting incident CVD; (2) the value with the smallest probability value associated with incident CVD; and (3) visual inspection of functions of LVMI and CVD in the general additive model (GAM) plot. At a median follow-up of 6.8 years, there were 192 events (coronary heart disease=87, stroke=62, and congestive heart failure=43; incidence=17.6/1000 person-years). The best operating point from the resulting ROC analysis was 51.2 g/m
2.7
for sensitivity (53.4%) and specificity (61.5%). The Cox and GAM models adjusted for age, gender, systolic blood pressure, hypertension, diabetes, smoking, total cholesterol-to-high-density lipoprotein ratio, LVH by ECG criterion, and socioeconomic status found 50 to 51 g/m
2.7
as the optimal threshold for LVH in middle-aged blacks, corresponding to a minimum probability value and to a log-hazard ratio of zero, respectively. Because these values are close to the 51 g/m
2.7
established from predominantly white populations, this cutpoint is appropriate for both groups.
Birth Weight and Blood Pressure in Childhood
Authors: Primatesta Paola , Falaschetti E. , Poulter Neil R.
Published: November 2004

Findings of previous reports relating low birth weight with raised blood pressure in childhood and adolescence have been inconsistent. The present study uses cross-sectional data from a series of nationally representative annual surveys—the Health Survey for England—between 1995 and 2002, totaling a sample of 15 629 children aged 5 to 15. A significant negative relationship between birth weight, in quartiles or dichotomized as low (<2.5 kg) and normal (≥2.5 kg) and systolic blood pressure was apparent. Linear regression analyses confirmed these findings. When current weight was included in the model, the strength of the relationship increased. An interaction term between birth weight and current weight was not significant. A life-course plot for those aged 13 to 15 (n=3900), converting the weight measurements at birth and as a teenager to standard deviation scores to make the regression coefficients comparable, showed the importance of weight gain on blood pressure (1 standard deviation increase in weight from birth to age 13 to 15 was associated with an increase in systolic blood pressure of 0.8 mm Hg). Separating those with low and normal birth weight demonstrated that the increase in weight from birth to adolescence had an effect on blood pressure in both those with low and normal birth weight. Postnatal changes in size have a more important effect on blood pressure in childhood and adolescence than birth weight. Reducing the prevalence of overweight among children may reduce their systolic blood pressure importantly and, particularly among children with lower birth weight, the prevalence of hypertension later in life.
Signaling via the Angiotensin-Converting Enzyme Enhances the Expression of Cyclooxygenase-2 in Endothelial Cells
Authors: Kohlstedt Karin , Busse Rudi , Fleming Ingrid
Published: November 2004

Angiotensin-converting enzyme (ACE) inhibitors elicit outside-in signaling via ACE in endothelial cells. This involves the CK2-mediated phosphorylation of ACE on Ser
1270
and the activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway, resulting in an enhanced endothelial ACE expression. Because cyclooxygenase-2 (COX-2) expression is reported to be increased in subjects treated with ACE inhibitors, we determined the role of ACE signaling in this phenomenon and the transcription factors involved. In lungs from mice treated with the ACE inhibitor ramipril for 5 days, COX-2 expression was increased. A similar (1.5- to 2-fold) increase in COX-2 protein was detected in primary cultures of human endothelial cells treated with ramiprilat. In an endothelial cell line stably expressing human somatic ACE, ramiprilat increased COX-2 promoter activity, an effect not observed in ACE-deficient cells or cells expressing a nonphosphorylatable ACE mutant (S1270A). The ramiprilat-induced, ACE-dependent increase in COX-2 expression and promoter activity (both 1.5- to 2-fold greater than control) was prevented by the inhibition of JNK. Ramiprilat significantly enhanced the DNA binding activity of activator protein-1 in cells expressing ACE but not S1270A ACE. Activator protein-1 decoy oligonucleotides prevented the ACE inhibitor-induced increase in COX-2 promoter activity and protein expression. As a consequence of the ramiprilat-induced increase in COX-2 expression, prostacyclin and prostaglandin E
2
, but not thromboxane A
2
, production was increased and was inhibited by the COX-2 inhibitor celecoxib. These results indicate that ACE signaling may underlie the increase in COX-2 and prostacyclin levels in patients treated with ACE inhibitors.
Childhood Uric Acid Predicts Adult Blood Pressure
Authors: Alper Arnold B. , Chen Wei , Yau Lillian , Srinivasan Sathanur R. , Berenson Gerald S. , Hamm L. Lee
Published: November 2004

Uric acid has been proposed as an important risk factor in the development of primary hypertension in humans. However, limited information is available linking childhood uric acid levels and blood pressure levels in adulthood. This study examined 334 whites and 243 blacks enrolled in the Bogalusa Heart Study as children aged 5 to 17 years and as adults aged 18 to 35 years. The average follow-up period was 12 years. Childhood uric acid was significantly correlated with childhood and adult blood pressure, both systolic and diastolic. In a multivariate regression analysis, adjusting for age, sex, race, childhood body mass index, childhood uric acid levels, and change in levels of uric acid were significant predictors of adult diastolic blood pressure, whereas change in uric acid was a significant predictor of adult systolic blood pressures. In conclusion, elevated childhood serum uric acid levels are associated with increased blood pressure beginning in childhood and higher blood pressure levels that persist into adulthood, in males and females, whites and blacks, suggesting that early elevations in serum uric acid levels may play a key role in the development of human hypertension.
Prediction of Heart Failure by Amino Terminal-pro–B-Type Natriuretic Peptide and C-Reactive Protein in Subjects With Cerebrovascular Disease
Authors: Campbell Duncan J. , Woodward Mark , Chalmers John P. , Colman Samuel A. , Jenkins Alicia J. , Kemp Bruce E. , Neal Bruce C. , Patel Anushka , MacMahon Stephen W.
Published: November 2004

B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal–pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure–lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor–based therapy.
Characteristics of Prolonged Ca
2+
Release Events Associated With the Nuclei in Adult Cardiac Myocytes
Authors: Yang Zhaokang , Steele Derek S.
Published: November 2004

Confocal microscopy was used to study the properties of nuclear Ca
2+
regulation in adult ventricular myocytes. Prolonged nuclear Ca
2+
release (PNCR) events were identified in both intact and permeabilized rat myocytes. PNCR occurred spontaneously and was restricted to localized regions at the ends of the elongated nuclei. Typically, PNCR took the form of a rapid rise in [Ca
2+
] followed by a maintained plateau. The mean duration of PNCR (1.78±0.19 seconds) was markedly greater than the half decay time for cytosolic Ca
2+
sparks (31.2±0.56 ms) obtained under the same conditions. The PNCR width at half maximum amplitude (5.0±0.2 μm) was also significantly greater than that of cytosolic Ca
2+
sparks (2.6±0.05 μm) obtained under the same conditions. Experiments involving the use of syto-11 to accurately locate the nuclei demonstrated that PNCR originates from the nuclear envelope or a closely associated structure. The spatial spread of PNCR was asymmetrical, with greater diffusion of Ca
2+
toward the center of the nucleus than the cytosol. Both PNCR and Ca
2+
sparks were abolished by interventions that deplete SR Ca
2+
stores or inhibit RYR activation. Experiments on intact, electrically stimulated cells revealed that diffusion of Ca
2+
from the ends of the nucleus toward the center is a prominent feature of the nucleoplasmic Ca
2+
transient. The possibility that recruitment of Ca
2+
release sites involved in PNCR might influence the temporal and spatial characteristics of the nucleoplasmic [Ca
2+
] transient is considered.
Bone Marrow Cells Differentiate in Cardiac Cell Lineages After Infarction Independently of Cell Fusion
Authors: Kajstura Jan , Rota Marcello , Whang Brian , Cascapera Stefano , Hosoda Toru , Bearzi Claudia , Nurzynska Daria , Kasahara Hideko , Zias Elias , Bonafé Massimiliano , Nadal-Ginard Bernardo , Torella Daniele , Nascimbene Angelo , Quaini Federico , Urbanek Konrad , Leri Annarosa , Anversa Piero
Published: November 2004

Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit–positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.