bluuebunny/crossref_metadata_2025 huggingface dataset:
A COMPUTATIONAL-RAM (C-RAM) ARCHITECTURE FOR REAL-TIME MESH-BASED VIDEO MOTION TRACKING PART 2: MOTION COMPENSATION
Authors: SAYED MOHAMMED , BADAWY WAEL
Published: May 2005

This paper presents a new Computational-RAM (C-RAM) architecture for real-time mesh-based video motion tracking. In Part 1, the motion estimation part of the proposed architecture is presented. Here in Part 2, a new C-RAM mesh-based motion compensation architecture is presented. The input data to the architecture is the mesh nodes motion vectors and the reference frame and the output data is the compensated (i.e., predicted) frame. The architecture uses the affine transformation for warping the deformed patches in the reference frame into the undeformed patches in the current frame. The architecture computes the affine parameters using a multiplication-free algorithm. The reference and current frames are stored in embedded S-RAMs generated with Virage™ Memory Compiler. The proposed motion compensation architecture has been prototyped, simulated and synthesized using the TSMC 0.18 μm CMOS technology. Using 100 MHz clock frequency, the proposed architecture processes one CIF video frame (i.e., 352×288 pixels) in 0.59 ms, which means it can process up to 1694 frames per second. The core area of the proposed motion compensation architecture is 28.04 mm2 and it consumes 31.15 mW.
ON A BI-LAYER SHALLOW WATER MODEL WITH RIGID-LID HYPOTHESIS
Authors: DI MARTINO B. , ORENGA P. , PEYBERNES M.
Published: May 2005

In this paper, we present a new model for a bi-layer shallow water problem using the rigid-lid hypothesis. This model follows from the usual bi-layer model and can drastically decrease the computational time of simulation. But some mathematical and numerical difficulties appear. Particularly, we observe in the equations some terms in the form of 1/hi (where hi is the thickness of the layer) and we are not able to prove that hi > 0. To circumvent this difficulty, we replace in these terms hi by Hi > β > 0, where Hi is a characteristic thickness of the layer. This hypothesis is realistic if the fluctuations of hi are small, which is generally the case. Then, we prove existence and regularity results for this approximated problem which shows the convergence of the numerical scheme. Next, we present some comparative results in an idealized configuration between this model and the classical bi-layer shallow water model.
DISCONTINUOUS/CONTINUOUS LEAST-SQUARES FINITE ELEMENT METHODS FOR ELLIPTIC PROBLEMS
Authors: BENSOW RICKARD E. , LARSON MATS G.
Published: May 2005

Least-squares finite element methods (LSFEM) are useful for first-order systems, where they avoid the stability consideration of mixed methods and problems with constraints, like the div-curl problem. However, LSFEM typically suffer from requirements on the solution to be very regular. This rules out, e.g., applications posed on nonconvex domains. In this paper we study a least-squares formulation where the discrete space is enriched by discontinuous elements in the vicinity of singularities. The weighting on the interelement terms are chosen to give correct regularity of the solution space and thus making computation of less regular problems possible. We apply this technique to the first-order Poisson problem, show coercivity and a priori estimates, and present numerical results in 3D.
A DIRECTOR THEORY APPROACH FOR MODELING BLOOD FLOW IN THE ARTERIAL SYSTEM: AN ALTERNATIVE TO CLASSICAL 1D MODELS
Authors: ROBERTSON ANNE M. , SEQUEIRA ADÉLIA
Published: May 2005

It remains computationally infeasible to model the full three-dimensional (3D) equations for blood flow in large sections of the circulatory system. As a result, one-dimensional (1D) and lumped parameter models play an important role in studies of the arterial system. A variety of 1D models are used, distinguished by the closure approximations employed. In this paper, we introduce a nine-director theory for flow in axisymmetric bodies as an alternative to the 1D models. Advantages of the director theory include (i) the theory makes use of all components of linear momentum; (ii) the flow is not assumed to be uni-directional; (iii) the theory is hierarchical; (iv) there is no need for closure approximations; and (v) wall shear stress enters directly as a dependent variable. In order to simplify the equations for mathematical analysis, for this work, attention is focused on cases where it is appropriate to model the flow as quasi-steady and the wall motion does not have a significant impact on bulk flow parameters. This work lays the foundation for future applications of the theory to unsteady flows in flexible walled vessels. For the geometries considered here, the nine-director theory has the same advantage as 1D models in providing a relatively simple relation between flow rate and average pressure drop. Conditions for existence, uniqueness and local stability of steady solutions are determined for both the 1D and nine-director equations. The predictive capability of classical 1D models found in the recent literature and a nine-director model7,15 are carefully evaluated through comparison with analytical and computational solutions to the axisymmetric, steady Navier–Stokes equations in geometries relevant to blood flow. For these benchmark problems over the range of Reynolds numbers considered, the nine-director theory is found to provide better results than the classical 1D models. A novel approach for parameter identification is in the 1D model is given and shown to substantially improve its predictive capability in these test cases.
LITTLEWOOD–PALEY THEORY AND REGULARITY ISSUES IN BOLTZMANN HOMOGENEOUS EQUATIONS I: NON-CUTOFF CASE AND MAXWELLIAN MOLECULES
Authors: ALEXANDRE RADJESVARANE , SAFADI MOUHAMAD EL
Published: May 2005

We use Littlewood–Paley theory for the analysis of regularization properties of solutions of the homogeneous Boltzmann equation. For non-cutoff Maxwellian molecules, we show that such solutions are smoother than the initial data. Although the recent and up to date results of Desvillettes and Wennberg10 assume much more general assumptions on the collision cross sections, our method seems to be simpler than those used earlier to show such properties and also applies to any weak solution.
SIMPLE, BASIC, MECHANISMS THAT ENHANCE OR DIMINISH THE CONCENTRATION OF SELECTED METABOLITES WITHIN METABOLISING BIOLOGICAL SYSTEMS
Authors: TIENARI JUKKA
Published: May 2005

An attempt is made for pedagogical purposes to construct a model as simple as possible for analyzing biochemical control mechanisms that participate in the selection of molecules in biological systems. The analysis is simplified by an assumption that the system is in a steady state. The mechanisms result from the principle that in an open system the absolute rate constants determine the proportions of components. Reactions producing or consuming substances that influence the rates of other reactions in the system also influence the amounts of participating substances. Reciprocal effects result in internal control which selects some substances by increasing their relative amounts. Similar mechanisms also control processes other than chemical reactions. The selection contributes to the maintenance of the non-random distribution of molecules in the biosphere that allows certain biological molecules to be more abundant than other molecules consisting of the same elements and having comparable standard free energies of formation.
DYNAMIC ANALYSIS OF A HOLLING I PREDATOR-PREY SYSTEM WITH MUTUAL INTERFERENCE CONCERNING PEST CONTROL
Authors: ZHANG YUJUAN , XU ZHILONG , LIU BING , CHEN LANSUN
Published: May 2005

A Holling I predator-prey model with mutual interference concerning pest control is proposed and analyzed. The prey and predator are considered to be a pest and a natural enemy, respectively. The model is forced by the addition of periodic impulsive terms representing predator import (biological control) and pesticide application (chemical control) at different fixed moments. By using Floquet theory and small amplitude perturbations, we show the existence and stability of pest-free periodic solutions. Further, we prove that when the stability of pest-free periodic solutions is lost, the system is permanent by using analytic methods of differential equation theory. Numerical solutions are also given, which show that when stability of pest-free periodic solutions is lost, more exotic behavior can occur, such as quasi-periodic oscillation or chaos. We investigate the effect of impulsive perturbations on the unforced continuous system, and find that the forced system has a different dynamical behavior with a different range of initial values which are inside or outside the unstable limit cycle of the unforced continuous system. Finally, we compare the validity of the combination of biological control and chemical control with classical methods and conclude that the synthetical strategy is more effective than classical methods if we take effective chemical control.
THE EFFECT OF IMPULSIVE SPRAYING PESTICIDE ON STAGE-STRUCTURED POPULATION MODELS WITH BIRTH PULSE
Authors: LIU BING , TENG ZHIDONG , CHEN LANSUN
Published: May 2005

In most models of population dynamics, increases in population due to birth are assumed to be time dependent, but many species reproduce only a single period of the year. In this paper, we construct a stage-structured pest model with birth pulse and periodic spraying pesticide at fixed time in each birth period by using impulsive differential equation. Using the discrete dynamical system determined by the stroboscopic map, we obtain an exact periodic solution of systems which are with Ricker function or Beverton-Holt function, and obtain the threshold conditions for their stability. Further, we show that the time of spraying pesticide has a strong impact on the number of the mature pest population. Our results imply that the best time of spraying pesticide is at the end of the season, that is before and near the time of birth. Finally, by numerical simulations we find that the dynamical behaviors of the stage-structured population models with birth pulse and impulsive spraying pesticide are very complex, including period-doubling cascade, period-halving cascade, chaotic bands with periodic windows and "period-adding" phenomena.
BALANCED FUZZY COMPUTING UNIT
Authors: HOMENDA WLADYSLAW , PEDRYCZ WITOLD
Published: May 2005

We introduce and study a new concept of fuzzy computing units. This construct is is aimed at coping with "negative" (inhibitory) information and accommodating it in the language of fuzzy sets. The essential concept developed in this study deals with computing units exploiting the concept of balanced fuzzy sets. We recall how the membership notion of fuzzy sets can be extended to the [-1,1] range giving rise to balanced fuzzy sets and then summarize properties of augmented (extended) logic operations for these constructs. We show that this idea is particularly appealing in neurocomputing as the "negative" information captured through balanced fuzzy sets exhibits a straightforward correspondence with inhibitory processing mechanisms encountered in neural networks. This gives rise to interesting properties of balanced computing units when compared with fuzzy and logic neurons developed on the basis of classical logic and classical fuzzy sets. Illustrative examples concerning topologies and properties and learning of balanced fuzzy computing units are included. A number of illustrative examples concerning topologies, properties and learning of balanced fuzzy fuzzy computing units are included.
IMPRECISE SECOND-ORDER MODEL FOR A SYSTEM OF INDEPENDENT RANDOM VARIABLES
Authors: UTKIN LEV V.
Published: May 2005

A new hierarchical uncertainty model for combining different evidence about a system of statistically independent random variable is studied in the paper. It is assumed that the first-order level of the model is represented by sets of lower and upper previsions (expectations) of random variables and the second-order level is represented by sets of lower and upper probabilities which can be viewed as confidence weights for interval-valued expectations of the first-order level. The model is rather general and allows us to compute probability bounds and "average" bounds for previsions of a function of random variables. A numerical example illustrates this model.
DOMINATION IN PRODUCTS OF FUZZY GRAPHS
Authors: SOMASUNDARAM A.
Published: May 2005

In this paper we discuss several operations on fuzzy graphs such as union, join, composition, Cartesian product and study their domination parameters.
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: KREINOVICH VLADIK
Published: May 2005

This section is maintained by Vladik Kreinovich. Please send your abstracts (or copies of papers that you want to see reviewed here) to vladik@cs.utep.edu, or by regular mail to: VLADIK KREINOVICH, Department of Computer Science, University of Texas at El Paso, El Paso, TX 79968, USA.
ANALYSIS OF AN INTERNAL FIXATION OF A LONG BONE FRACTURE
Authors: RAMAKRISHNA K. , SRIDHAR I. , SIVASHANKER S. , GANESH V. K. , GHISTA D. N.
Published: May 2005

A major concern when a fractured bone is fastened by stiff-plates to the bone on its tensile surface is excessive stress shielding of the bone. The compressive stress shielding at the fracture-interface immediately after fracture-fixation delays bone healing. Likewise, the tensile stress shielding of the healed bone underneath the plate also does not enable it to recover its tensile strength. Initially, the effect of a uniaxial load and a bending moment on the assembly of bone and plate is investigated analytically. The calculations showed that the screws near the fracture site transfers more load than the screws away from the fracture site in axial loading and it is found that less force is required when the screw is placed near to fracture site than the screw placed away from the fracture site to make the bone and plate bend with same radius of curvature when subjected to bending moment. Finally, the viability of using a stiffness graded bone-plate as a fixator is studied using finite element analysis (FEA): the stiffness-graded plate cause less stress-shielding than stainless steel plate.
JOINT ENERGY BALANCES: THE COMMITMENT TO THE SYNCHRONIZATION OF MEASURING SYSTEMS
Authors: GÜNTHER M. , WITTE H. , BLICKHAN R.
Published: May 2005

Our study quantifies the amount of error induced in the calculated energy balances of the joints if a trigger offset between the measurement of ground reaction force and of video data occurs. Joint energy balances constitute the basis for an adequate interpretation of muscular activity. An estimation of the amount of this error introduced by deficient synchronization has not been published so far but currently seems to be essential in the face of commercial providers offering complete solutions from data acquisition up to inverse dynamics analyses. As an example, we applied an inverse dynamics process to a data set of the contact phase of human running where the synchronization was disturbed artificially. We compared the amount of error for different methods of inverse dynamics. We found that a time offset of 5 ms results in almost 100% error (compared to zero offset) in the energy balance of each joint (up to 28 J in the hip). A kinematic event appearing later on the time scale than the respective kinetics shifts the calculated main source of energy production from the ankle to the hip, and vice versa if appearing precipitate. This 5 ms synchronization error is even higher than the methodical error introduced when synchronizing correctly but using the static torque equilibrium instead of complex inverse dynamics for the calculation of joint torques. We conclude that when buying professional analysis systems a strong urge to prove exact synchronization should be put on the provider.
ADAPTIVE BONE REMODELING CRITERIA APPLIED TO DESIGN OPTIMIZATION OF FEMORAL COMPONENT OF HIP PROSTHESES
Authors: KATOOZIAN HAMID , BARANI ZOHREH , DAVY DWIGHT T.
Published: May 2005

Considering effects of physiological factors in failure of total hip arthroplasty, a numerical procedure was implemented for the three-dimesional (3D) shape optimization of femoral component of total hip replacements on the basis of remodeling objective functions. Design variables are the shape parameters, which define the femoral component geometry. The 3D design model was incorporated with 3D finite element analysis and a numerical optimization procedure. The main optimization goal was to reduce the potential for change of the bone morphology and to keep it close to the normal condition of an intact femur, by changing the geometry of the implant. Both local and global remodeling goals were examined. The results suggest a much more slender implant than is normally used would be required to minimize the remodeling potential. The results also demonstrated that the outcomes are indeed sensitive to whether the remodeling goal is treated as local or global.
Endogenous ATP Involvement in Mustard-Oil-Induced Central Sensitization in Trigeminal Subnucleus Caudalis (Medullary Dorsal Horn)
Authors: Chiang C. Y. , Zhang S. , Xie Y. F. , Hu J. W. , Dostrovsky J. O. , Salter M. W. , Sessle B. J.
Published: May 2005

Central sensitization represents a sustained hypersensitive state of dorsal horn nociceptive neurons that can be evoked by peripheral inflammation or injury to nerves and tissues. It reflects neuroplastic changes such as increases in neuronal spontaneous activity, receptive field size, and responses to suprathreshold stimuli and a decrease in activation threshold. We recently demonstrated that purinergic receptor mechanisms in trigeminal subnucleus caudalis (Vc; medullary dorsal horn) are also involved in the initiation and maintenance of central sensitization in brain stem nociceptive neurons of trigeminal subnucleus oralis. The aim of the present study was to investigate whether endogenous ATP is involved in the development of central sensitization in Vc itself. The experiments were carried out on urethan/α-chloralose anesthetized and immobilized rats. Single neurons were recorded and identified as nociceptive-specific (NS) in the deep laminae of Vc. During continuous saline superfusion (0.6 ml/h it) over the caudal medulla, Vc neuronal central sensitization was readily induced by mustard oil application to the tooth pulp. However, this mustard-oil-induced central sensitization could be completely blocked by continuous intrathecal superfusion of the wide-spectrum P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetra-sodium (33–100 μM) and by apyrase (an ectonucleotidase enzyme, 30 units/ml). Superfusion of the selective P2X1, P2X3 and P2X2/3 receptor antagonist 2′,3′- O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate (6–638 μM) partially blocked the Vc central sensitization. The two P2X receptor antagonists did not significantly affect the baseline nociceptive properties of the Vc neurons. These findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.
Localization and Expression of R-Cadherin in Skeletal Muscle following Nerve Injury
Authors: Niitsuma K. , Hatoko M. , Kuwahara M. , Tanaka A. , Yurugi S. , Iioka H.
Published: May 2005

Rats in which the sciatic nerves were cut were divided into two groups: animals with nerve sutured and animals with nerve not sutured. In the unsutured group, the levels of R-cadherin expression increased and then decreased to values lower than those of controls. In the sutured group, the levels of R-cadherin expression increased and then decreased to almost control values. These results suggest that R-cadherin plays some role in cells of normal and regenerating muscles.
Efficacy of Low-Dose FK506 in the Treatment of Myasthenia gravis – A Randomized Pilot Study
Authors: Nagane Yuriko , Utsugisawa Kimiaki , Obara Daiji , Kondoh Ryushi , Terayama Yasuo
Published: May 2005

To determine the efficacy of low-dose FK506 in the treatment of myasthenia gravis (MG), untreated de novo patients were randomly selected to receive treatment with (n = 18) or without (n = 16) FK506, and were evaluated for 1 year after treatment with limitation of daily dose of prednisolone. Low-dose FK506 reduced the duration of early-phase therapy in hospital (p < 0.05) and the need for combined therapy with plasmapheresis and high-dose intravenous methylprednisolone or high-dose intravenous methylprednisolone alone (p < 0.05). It also reduced the daily dose of prednisolone (p < 0.05) required to maintain minimal manifestations of MGFA postintervention status. None of the patients exhibited significant side effects up to 1 year after treatment. These findings suggest that low-dose FK506 is safe and efficacious for the treatment of de novo MG patients.
Thyroid Function, Cytokine and IGF-IGFBP Interactions in Cystic Fibrosis Patients
Authors: Volta Cecilia , Street Maria Elisabeth , Ziveri Maria Angela , Bonelli Patrizia , Spaggiari Cinzia , Grzincich Gian Luigi , Bernasconi Sergio
Published: May 2005

Background/Aims: Thyroid function impairment has been sporadically described in cystic fibrosis (CF) and ascribed to iodine overload or selenite deficiency. In this study we evaluated thyroid function in CF in order to verify these data and to evaluate if the modifications were related to serum levels of markers of inflammation and growth factors that we have previously shown to be altered in CF. Methods: Seventeen young adult CF patients and 18 age-matched controls were enrolled in this study. The diagnosis of CF was confirmed by genetic analysis. None was treated with pulmonary expectorants. Serum IL-1β, IL-6, TNF-α, IGF-I, IGF-II, IGFBP-2, IGFBP-3, TSH, fT3 and fT4 were measured using standard commercial kits. Results: TSH, fT3 and fT4 serum levels were similar in CF patients and controls. Within the patient group, thyroid function did not vary in relation to C-reactive protein serum levels, respiratory function and clinical conditions (Shwachman score). No correlation was found with any growth factor or cytokine analyzed. Conclusions: At variance with the few previously published data, we did not detect any difference in thyroid function in patients with CF compared with normal healthy subjects. This could be due to the fact that no iodine overload or selenite deficiency was present in our patients. Thyroid function seemed independent of markers of inflammation and IGF-IGFBP serum levels.
Effects of Weight Loss in Overweight/Obese Individuals and Long-Term Hypertension Outcomes
Authors: Aucott Lorna , Poobalan Amudha , Smith W. Cairns S. , Avenell Alison , Jung Roland , Broom John
Published: May 2005

Many studies have assessed short-term effects of weight loss on blood pressure, whereas little attention has been paid to long-term effects. We conducted a systematic review to evaluate the long-term effects of weight loss on hypertension outcome measures in adults using literature published from 1966 to 2001. All prospective studies and trials, performed on participants with body mass index of ≥28 kg/m
2
with a follow-up of >2 years and weight changes recorded, were included. The data from these studies were used to model the long-term effects on blood pressure. Previous reviews on shorter-term studies indicate a 1:1 drop in blood pressure (mm Hg) with weight loss (kilograms). Our findings, based on studies with follow-up of ≥2 years, demonstrate blood pressure decreases less than this after weight loss. The surgical intervention studies exhibited huge weight losses with undramatic blood pressures changes. When surgical interventions are excluded, the models suggest that for 10 kg weight loss, decreases of 4.6 mm Hg and 6.0 mm Hg in diastolic and systolic blood pressure, respectively, may be expected, about half of that predicted from the short-term trials. Initial blood pressure, the length of follow-up, medication changes, and physiological restrictions may contribute to this reduced effect in the long-term studies. Extrapolation of short-term blood pressure changes with weight loss to the longer term is potentially misleading. The weight/hypertension relationship is complex and needs well-conducted studies with long-term follow-up to examine the effects of weight loss on hypertension outcomes.
Effect of Body Mass Index Changes Between Ages 5 and 14 on Blood Pressure at Age 14
Authors: Mamun Abdullah A. , Lawlor Debbie A. , O’Callaghan Michael J. , Williams Gail M. , Najman Jake M.
Published: May 2005

Weight reduction in clinical populations of severely obese children has been shown to have beneficial effects on blood pressure, but little is known about the effect of weight gain among children in the general population. This study compares the mean blood pressure at 14 years of age with the change in overweight status between ages 5 and 14. Information from 2794 children born in Brisbane, Australia, and who were followed up since birth and had body mass index (BMI) and blood pressure measurements at ages 5 and 14 were used. Systolic and diastolic blood pressure at age 14 was the main outcomes and different patterns of change in BMI from age 5 to 14 were the main exposure. Those who changed from being overweight at age 5 to having normal BMI at age 14 had similar mean blood pressures to those who had a normal BMI at both time points: age- and sex-adjusted mean difference in systolic blood pressure 1.54 (−0.38, 3.45) mm Hg and in diastolic blood pressure 0.43 (−0.95, 1.81) mm Hg. In contrast, those who were overweight at both ages or who had a normal BMI at age 5 and were overweight at age 14 had higher blood pressure at age 14 than those who had a normal BMI at both times. These effects were independent of a range of potential confounding factors. Our findings suggest that programs that successfully result in children changing from overweight to normal-BMI status for their age may have important beneficial effects on subsequent blood pressure.
Kidney in Early Atherosclerosis
Authors: Chade Alejandro R. , Lerman Amir , Lerman Lilach O.
Published: May 2005

Atherosclerosis represents one of the major causes of premature death in the United States today, and it is frequently associated with, exacerbates, and is aggravated by chronic kidney disease (CKD). Atherosclerosis integrates the response to a number of insults, and consequently, the accelerated atherosclerosis found in CKD patients is associated with activation of a variety of humoral and tissue mechanisms. Hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome, and additional nontraditional risk factors can damage the kidney directly and by promoting intrarenal atherogenesis, even in the absence of obstructive lesions in the renal artery. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. In turn, progressive deterioration of renal function in CKD may lead to dyslipidemia or accumulation of uremic toxins, which can induce production of free radicals and activate proinflammatory and fibrogenic factors, leading to vascular endothelial cell dysfunction and injury, and favoring development of atherosclerosis. Therefore, the kidney can be a villain or a victim during atherogenesis. The purpose of this review is to provide new insights into the mechanisms by which atherogenic factors may instigate early renal injury.
Contribution of Arachidonic Acid Metabolites Derived Via Cytochrome P4504A to Angiotensin II–Induced Neointimal Growth
Authors: Yaghini Fariborz A. , Zhang Chunxiang , Parmentier Jean-Hugues , Estes Anne M. , Jafari Nauzanene , Schaefer Susan A. , Malik Kafait U.
Published: May 2005

Angiotensin II and the arachidonic acid metabolite derived via cytochrome P450 20-hydroxyeicostetraenoic acid promote vasoconstriction and vascular smooth muscle cell (VSMC) proliferation. This study was conducted to determine if 20-hydroxyeicostetraenoic acid contributes to angiotensin II-induced neointimal formation in balloon-injured rat carotid artery. In anesthetized rats, the drugs were infused into the clamped segment of the injured right common carotid artery for 60 minutes. The drug solution and catheter were withdrawn, the common carotid artery was ligated, and blood flow was restored. Exposure of the injured artery to angiotensin II (200 nmol/L) or arachidonic acid (10 μmol/L) increased neointimal thickening at day 14 (intima/media ratio 0.71±0.14 with vehicle versus 1.65±0.10 with angiotensin II or 1.31±0.13 with arachidonic acid;
P
<0.05). Cytochrome P450 4A1 antisense, but not scrambled, oligodeoxynucleotide (100 nmol/L) reduced angiotensin II-induced or arachidonic acid-induced neointimal thickening (intima/media ratio 0.90±0.07 for angiotensin II and 0.95±0.06 for arachidonic acid). 20-hydroxyeicostetraenoic acid (0.5 μmol/L) also increased neointimal thickening of injured artery (intima/media ratio 1.15±0.03); this was not altered by cytochrome P450 4A1 antisense oligodeoxynucleotide. Angiotensin II, arachidonic acid, and 20-hydroxyeicostetraenoic acid also induced the expression of cytochrome P450 4A and increased the number of CD45-positive cells; the latter effect of angiotensin II and arachidonic acid, but not 20-hydroxyeicostetraenoic acid, was diminished by cytochrome P450 4A1 antisense oligodeoxynucleotide. These data suggest that arachidonic acid metabolites derived via cytochrome P450 4A, most likely 20-hydroxyeicostetraenoic acid, mediate angiotensin II-induced neointimal thickening in injured rat carotid artery.
Augmented Input From Cardiac Sympathetic Afferents Inhibits Baroreflex in Rats With Heart Failure
Authors: Gao Lie , Schultz Harold D. , Patel Kaushik P. , Zucker Irving H. , Wang Wei
Published: May 2005

It has been established that the baroreflex is markedly decreased in chronic heart failure (CHF). Our recent study has indicated that activation of the cardiac sympathetic afferent reflex (CSAR) inhibits the baroreflex in normal rats, and in the rats with CHF the CSAR is significantly enhanced, which is related to augmented central angiotensin II (Ang II) mechanism. Therefore, the hypothesis is that the augmented CSAR in the CHF state tonically inhibits the baroreflex via central AT
1
receptor. To test the hypothesis, the rats with myocardial infarction-induced CHF or sham surgery were anesthetized with α-chloralose and urethane, vagotomized, and recordings were made of the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). We found: (1) left ventricular epicardial application of capsaicin or electrical stimulation of the central end of the left cardiac sympathetic nerve blunted the baroreflex in both sham and CHF rats; (2) left ventricular epicardial application of lidocaine had no significant effects on the baroreflex in sham rats but improved the baroreflex in CHF rats (maximum slope, 1.7±0.3 to 2.9±0.2%/mm Hg;
P
<0.01); and (3) intracerebral ventricular injection of losartan had no significant effect on baroreflex in sham rats but improved the baroreflex in CHF rats (maximum slope 1.9±0.2 to 3.1±0.2%/mm Hg;
P
<0.01). These results suggest that tonic cardiac sympathetic afferent input plays an important role in the blunted baroreflex associated with CHF, which is mediated by central AT
1
receptors.
Dual ECE/NEP Inhibition on Cardiac and Neurohumoral Function During the Transition From Hypertrophy to Heart Failure in Rats
Authors: Emoto Noriaki , Raharjo Sunu Budhi , Isaka Daiji , Masuda Shigeru , Adiarto Suko , Jeng Arco Y. , Yokoyama Mitsuhiro
Published: May 2005

CGS 26303 is a vasopeptidase inhibitor that simultaneously inhibits endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). We compared the effects of chronic treatment with CGS 26303 to the selective inhibition of angiotensin-converting enzyme (ACE) and NEP during the transition from left ventricular hypertrophy (LVH) to congestive heart failure (CHF) in hypertensive rats. LV geometry and function were assessed in Dahl salt-sensitive rats placed on a high-salt diet from age 6 weeks (hypertensive rats) and in control rats fed a low-salt diet. The hypertensive rats were randomized into groups that received no treatment or were treated with an ACE inhibitor (temocapril), an ECE/NEP inhibitor (CGS 26303), or a NEP inhibitor (CGS 24592) from the LVH stage (11 weeks) to the CHF stage (17 weeks). All treatments decreased the systolic blood pressure equally and significantly improved LV fractional shortening. Both temocapril and CGS 26303 ameliorated LV perivascular fibrosis, reduced mRNA levels of types I and III collagen, and decreased the heart weight/body weight ratio. CHF rats had increased plasma ET-1 levels compared with control rats. Only CGS 26303 reduced ET-1 to normal levels. ET-1 levels were found to correlate with heart/body weight, right ventricle/body weight and perivascular fibrosis ratios. During the transition to CHF, CGS 26303 produces effects that are comparable to temocapril and superior to CGS 24592. The beneficial effects of CGS 26303 are likely caused in part by the greater reduction of plasma ET-1. Dual ECE/NEP inhibitor may provide a new strategy for the treatment of human heart failure.
Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture
Authors: Ahimastos Anna A. , Natoli Alaina K. , Lawler Adam , Blombery Peter A. , Kingwell Bronwyn A.
Published: May 2005

Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid–femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10±0.02 mL/mm Hg, (
P
<0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7±0.2 m/s (
P
<0.001), augmentation index by 4.1±0.3% (
P
<0.001), and systolic blood pressure by 5±1 mm Hg (
P
<0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (
P
=0.59). In cell culture, ramiprilat decreased collagen deposition by >50% and increased elastin and fibrillin-1 deposition by >3- and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.
Association of Hypoadiponectinemia With Smoking Habit in Men
Authors: Iwashima Yoshio , Katsuya Tomohiro , Ishikawa Kazuhiko , Kida Iwao , Ohishi Mitsuru , Horio Takeshi , Ouchi Noriyuki , Ohashi Koji , Kihara Shinji , Funahashi Tohru , Rakugi Hiromi , Ogihara Toshio
Published: May 2005

Adiponectin is emerging as an important molecule in obesity, the metabolic syndrome, and cardiovascular disease. On the other hand, smoking habit is well known to be related to cardiovascular disease and hypertension. To examine the association between adiponectin concentration and smoking habit, we performed an epidemiological survey and an acute exposure test in humans and an experiment in adipocytes to elucidate the mechanism underlying the association between adiponectin and smoking. In the epidemiological study, we enrolled a total of 331 male subjects to examine chronic smoking exposure. Plasma adiponectin was significantly lower (
P
=0.01) in current smokers (5.3±0.3 μg/mL) than in never-smokers (6.5±0.4 μg/mL). A significant association between smoking and low adiponectin level was also confirmed in multiple regression analysis including age, body mass index, hypertension, diabetes, hyperlipidemia, and creatinine clearance (never-smokers 6.5±0.4 μg/mL; past smokers 5.6±0.3 μg/mL; current smokers 5.2±0.4 μg/mL;
F
=4.52;
P
=0.01). To examine the acute effect of smoking on adiponectin concentration for 12 hours, we measured plasma adiponectin level in 5 male never-smokers before smoking and 3, 6, and 12 hours after smoking, with the result that adiponectin showed a significant decrease after smoking (12 hours; −14.5±0.6%;
P
<0.01). In cultured mouse 3T3-L1 adipocytes, H
2
O
2
and nicotine reduced the mRNA expression and secretion of adiponectin in a dose-dependent manner. Smoking habit is associated with adiponectin concentration in men, and its suppressive effect is mediated in part through direct inhibition of smoking on adiponectin expression in adipocytes.
Identification and Characterization of Two Genes (MIP-1β, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation
Authors: Roussoulières A.L.S. , Raisky O. , Chalabreysse L. , Dureau G. , Cerutti C. , Thieblemont C. , Boissonnat P. , Sebbag L. , Obadia J.-F. , Ninet J. , Bastien O. , Thivolet-Bejui F. , McGregor J.L.
Published: May 2005

Background—

Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection.

Methods and Results—

Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1β (MIP-1β), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model.

Conclusions—

We have demonstrated that the upregulation of MIP-1β and downregulation of VE-cadherin may strongly participate in human acute heart rejection.
Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2
Authors: Ferrario Carlos M. , Jessup Jewell , Chappell Mark C. , Averill David B. , Brosnihan K. Bridget , Tallant E. Ann , Diz Debra I. , Gallagher Patricia E.
Published: May 2005

Background—

Angiotensin-converting enzyme 2 (ACE2) has emerged as a novel regulator of cardiac function and arterial pressure by converting angiotensin II (Ang II) into the vasodilator and antitrophic heptapeptide, angiotensin-(1–7) [Ang-(1–7)]. As the only known human homolog of ACE, the demonstration that ACE2 is insensitive to blockade by ACE inhibitors prompted us to define the effect of ACE inhibition on the ACE2 gene.

Methods and Results—

Blood pressure, cardiac rate, and plasma and cardiac tissue levels of Ang II and Ang-(1–7), together with cardiac ACE2, neprilysin, Ang II type 1 receptor (AT
1
), and
mas
receptor mRNAs, were measured in Lewis rats 12 days after continuous administration of vehicle, lisinopril, losartan, or both drugs combined in their drinking water. Equivalent decreases in blood pressure were obtained in rats given lisinopril or losartan alone or in combination. ACE inhibitor therapy caused a 1.8-fold increase in plasma Ang-(1–7), decreased plasma Ang II, and increased cardiac ACE2 mRNA but not cardiac ACE2 activity. Losartan increased plasma levels of both Ang II and Ang-(1–7), as well as cardiac ACE2 mRNA and cardiac ACE2 activity. Combination therapy duplicated the effects found in rats medicated with lisinopril, except that cardiac ACE2 mRNA fell to values found in vehicle-treated rats. Losartan treatment but not lisinopril increased cardiac tissue levels of Ang II and Ang-(1–7), whereas none of the treatments had an effect on cardiac neprilysin mRNA.

Conclusions—

Selective blockade of either Ang II synthesis or activity induced increases in cardiac ACE2 gene expression and cardiac ACE2 activity, whereas the combination of losartan and lisinopril was associated with elevated cardiac ACE2 activity but not cardiac ACE2 mRNA. Although the predominant effect of ACE inhibition may result from the combined effect of reduced Ang II formation and Ang-(1–7) metabolism, the antihypertensive action of AT
1
antagonists may in part be due to increased Ang II metabolism by ACE2.
Risk Factors for Cardiovascular Disease in Homeless Adults
Authors: Lee Tony C. , Hanlon John G. , Ben-David Jessica , Booth Gillian L. , Cantor Warren J. , Connelly Philip W. , Hwang Stephen W.
Published: May 2005

Background—

Homeless people represent an extremely disadvantaged group in North America. Among older homeless men, cardiovascular disease (CVD) is the leading cause of death. The objective of this study was to examine cardiovascular risk factors in a representative sample of homeless adults and identify opportunities for improved risk factor modification.

Methods and Results—

Homeless persons were randomly selected at shelters for single adults in Toronto. Response rate was 79%. Participants (n=202) underwent interviews, physical measurements, and blood sampling. The mean age of participants was 42 years, and 89% were men. The prevalence of smoking among homeless subjects (78%; 95% confidence interval [CI], 72% to 84%) was significantly higher than in the general population (standardized morbidity ratio [SMR], 254; 95% CI, 216 to 297). Hypertension, high cholesterol, and diabetes were not more prevalent than in the general population but were often poorly controlled. Homeless men were significantly less likely to be overweight or obese than men in the general population (SMR, 79; 95% CI, 63 to 98). Cocaine use in the last year was reported by 29% of subjects (95% CI, 23% to 36%). CVD was reported by 15% of subjects, fewer than one third of whom reported taking aspirin or cholesterol-lowering medication. According to multiple-risk-factor equations, the median estimated 10-year absolute risk of myocardial infarction or coronary death among homeless men aged 30 to 74 years was 5% (interquartile range, 3% to 9%).

Conclusions—

Cardiovascular risk factor modification is suboptimal among homeless adults in Toronto, despite universal health insurance. Multiple risk factor equations may underestimate true risk in this population because of inadequate accounting for factors such as cocaine use and heavy smoking.
Delayed Preconditioning-Mimetic Actions of Nitroglycerin in Patients Undergoing Exercise Tolerance Tests
Authors: Jneid Hani , Chandra Mukul , Alshaher Motaz , Hornung Carlton A. , Tang Xian-Liang , Leesar Massoud , Bolli Roberto
Published: May 2005

Background—

Nitroglycerin (NTG) induces delayed preconditioning (PC)-mimetic effects in animal models and in humans during coronary angioplasty. We tested the hypothesis that NTG mitigates ischemia and enhances functional capacity during an exercise tolerance test (ETT) in patients with coronary artery disease.

Methods and Results—

Twenty-eight patients with stable angina and ischemia documented by a stress test were randomized in a double-masked, crossover design to receive a titrated intravenous infusion of NTG or normal saline over 4 hours. At 24 to 28 hours after study medication infusion, each patient underwent 2 ETTs separated by a 1-week washout period. Compared with control patients, pretreatment with NTG was associated with a dose-dependent increase in exercise duration averaging 40 seconds (412±19 versus 372±24 seconds,
P
=0.014) and an improvement in ECG manifestations of ischemia, as shown by a decrease in maximal ST-segment depression (1.84±0.14 versus 1.63±0.13 mm,
P
=0.011), sum of ST-segment depressions in 12 leads (7.64±1.01 versus 6.61±0.83 mm,
P
=0.027), and time to resolution of ST-segment depression (229±30 versus 207±28 s,
P
=0.018). These benefits occurred despite an increase in myocardial workload after NTG, as indicated by a higher peak rate-pressure product (24 492±1054 versus 22 536±1019 mm Hg/min,
P
=0.015).

Conclusions—

NTG produces a late PC-mimetic effect that mitigates the ECG manifestations of ischemia during exercise and improves exercise capacity. To our knowledge, this is the first study to demonstrate that NTG can alleviate exercise-induced ischemia 24 hours after its administration, long after the hemodynamic effects have subsided. The finding that nitrate-induced late PC ameliorates a common manifestation of coronary artery disease has potentially significant implications for the management of this disorder and for the design of clinical trials.
Precisely Exploring Medical Models and Volumes in Collaborative Virtual Reality
Authors: Silverstein Jonathan C. , Dech Fred
Published: May 2005

We describe a virtual-reality widget library and two medical applications built on the widget library. These two applications, education using surface models and radiological volume visualization, make use of collaborative interaction techniques. These techniques support a high degree of precision with respect to manipulation of data and data parameters. The 3D widgets instantiated in these applications are synchronized between clients in order to facilitate the high degree of interactivity necessary for productive investigation of shared medical models and volume data. We discuss challenges that face the investigator in an immersive 3D environment as opposed to that of a 2D desktop environment. We describe how these differences have led us to criteria for development of the shared 3D Virtual Reality (VR) graphical user interfaces (GUIs) used in the biomedical applications presented. We review our educational validations already conducted for the surface model exploration application and preview our future work toward a single advanced biomedical collaboration environment.
The Responses of People to Virtual Humans in an Immersive Virtual Environment
Authors: Garau Maia , Slater Mel , Pertaub David-Paul , Razzaque Sharif
Published: May 2005

This paper presents an experiment investigating the impact of behavior and responsiveness on social responses to virtual humans in an immersive virtual environment (IVE). A number of responses are investigated, including presence, copresence, and two physiological responses—heart rate and electrodermal activity (EDA). Our findings suggest that increasing agents' responsiveness even on a simple level can have a significant impact on certain aspects of people's social responses to human-oid agents.

Despite being aware that the agents were computer-generated, participants with higher levels of social anxiety were significantly more likely to avoid “disturbing” them. This suggests that on some level people can respond to virtual humans as social actors even in the absence of complex interaction.

Responses appear to be shaped both by the agents' behaviors and by people's expectations of the technology. Participants experienced a significantly higher sense of personal contact when the agents were visually responsive to them, as opposed to static or simply moving. However, this effect diminished with experienced computer users. Our preliminary analysis of objective heart-rate data reveals an identical pattern of responses.