bluuebunny/crossref_metadata_2025 huggingface dataset:
A MARKET OF INHOMOGENEOUS THRESHOLD CELLULAR AUTOMATA
Authors: STAUFFER DIETRICH , WEISBUCH GÉRARD
Published: January 2004

This article summarizes some physics aspects of the market model of Weisbuch and Stauffer, Physica A (2003): How do demand and quality expectation adjust to each other in a buyer dominated market like cinema visits? And how can business cycles be modelled?
CHAOTIC NETWORKS UNDER THRESHOLDING
Authors: SINHA SUDESHNA
Published: January 2004

We review some results on the phenomenology of networks of chaotic elements under threshold activated coupling. We show how thresholding at different levels gives rise to behaviour ranging from spatiotemporal cycles and spatiotemporal chaos, to scaling regimes reminiscent of self-organized criticality. We also indicate how our knowledge of the dynamical consequences of varying threshold levels can be used to design control algorithms targetting a wide range of spatiotemporal patterns. Some of these concepts are verified in experiments on chaotic electrical circuits.
A GENERALIZATION OF THE DETERMINISTIC ANNEALING EM ALGORITHM BY MEANS OF NON-EXTENSIVE STATISTICAL MECHANICS
Authors: INOUE JUN-ICHI , TABUSHI KATSUMI
Published: January 2004

We extend the EM algorithm to overcome its bottleneck, that is to say, the problem of local maxima of the marginal likelihood due to its strong dependence of initial conditions. As an alternative posterior distribution appearing in the so-called Q function, we use the distribution that maximizes the non-extensive Tsallis entropy. The distribution we introduce has a parameter q which represents the non-extensive property of the entropy. We control the parameter q so as to weaken the influence of the initial conditions. In order to investigate its performance, we apply our algorithm to Gaussian mixture estimation problems under some additive noises. In large data limit, we derive the averaged update equations with respect to hyper-parameters, marginal likelihood etc. analytically. Our analysis supports usefulness of our algorithm.
THEORY OF TOMOGRAPHY FOR THE WIGNER FUNCTION OF TRIPARTITE ENTANGLED SYSTEMS
Authors: FAN HONG-YI , JIANG NIAN-QUAN
Published: January 2004

Based on the observation that for an entangled-particles system, the physical meaning of the Wigner distribution function should lie in that its marginal distributions would give the probability of finding the particles in an entangled way, we establish a tomography theory for the Wigner function of tripartite entangled systems. The newly constructed tripartite entangled state representation of the three-mode Wigner operator plays a central role in realizing this goal.
EFFECT OF HOPPING AND ELECTRONIC CORRELATION ON ELECTRON–HOLE COUPLING IN DISORDERED SEMICONDUCTOR DOUBLE LAYER
Authors: YARTSEV V. M. , SINGH M. R. , DESFORGES J.
Published: January 2004

The effect of the hopping term in the formation of excitons is studied in semiconductor nanostructures where electrons and holes are spatially separated by a potential barrier. We use the lattice gas model where electron–hole system is divided into unit cells with the effective lattice constant being of the order of the exciton size. The exciton density is calculated as a function of the disorder for several fixed values of the hopping integral. It is found that as the value of the hopping integral increases the exciton density decreases rapidly both for weak and strong disorder. Electronic correlation is treated explicitly by introducing repulsion between equally charged carriers and attraction between an electron and a hole from neighboring cells.
DIMENSIONALITY EFFECTS IN TURING PATTERN FORMATION
Authors: LEPPÄNEN TEEMU , KARTTUNEN MIKKO , KASKI KIMMO , BARRIO RAFAEL A.
Published: January 2004

The problem of morphogenesis and Turing instability are revisited from the point of view of dimensionality effects. First the linear analysis of a generic Turing model is elaborated to the case of multiple stationary states, which may lead the system to bistability. The difference between two- and three-dimensional pattern formation with respect to pattern selection and robustness is discussed. Preliminary results concerning the transition between quasi-two-dimensional and three-dimensional structures are presented and their relation to experimental results are addressed.
STUDY OF FINITE SIZE EFFECTS ON DIRECTED SPIRAL PERCOLATION
Authors: SANTRA S. B.
Published: January 2004

Percolation under both directional and rotational constraints is studied numerically on the square lattice of different finite sizes L. The critical percolation threshold pc≈0.655 of the infinite network is determined by extrapolating the finite size data. The fractal dimension df of the infinite percolation clusters is found df≈1.72 from the finite size scaling, S∞~Ldf where S∞ is the mass of the infinite cluster. The critical exponents are estimated as a function of the system size L. It is seen that the results of smaller systems converge to that of the large systems. The results are then extrapolated to the infinite network. The extrapolated results for the infinite network are compared with Monte Carlo results on a single large lattice. A good agreement is found.
FAILURE PROPERTIES OF FIBER BUNDLE MODELS
Authors: PRADHAN SRUTARSHI , CHAKRABARTI BIKAS K.
Published: January 2004

We study the failure properties of fiber bundles when continuous rupture goes on due to the application of external load on the bundles. We take the two extreme models: equal load sharing model (democratic fiber bundles) and local load sharing model. The strength of the fibers are assumed to be distributed randomly within a finite interval. The democratic fiber bundles show a solvable phase transition at a critical stress (load per fiber). The dynamic critical behavior is obtained analytically near the critical point and the critical exponents are found to be universal. This model also shows elastic-plastic like nonlinear deformation behavior when the fiber strength distribution has a lower cut-off. We solve analytically the fatigue-failure in a democratic bundle, and the behavior qualitatively agrees with the experimental observations. The strength of the local load sharing bundles is obtained numerically and compared with the existing results. Finally we map the failure phenomena of fiber bundles in terms of magnetic model (Ising model) which may resolve the ambiguity of studying the failure properties of fiber bundles in higher dimensions.
DRIVEN RANDOM FIELD ISING MODEL: SOME EXACTLY SOLVED EXAMPLES IN THRESHOLD ACTIVATED KINETICS
Authors: SHUKLA PRABODH
Published: January 2004

The random field Ising Model (RFIM) driven by a slowly varying uniform external field at zero temperature provides a caricature of several threshold activated systems. In this model, the non-equilibrium response of the system can be obtained analytically in one dimension as well as on a Bethe lattice if the initial state of the system has all spins aligned parallel to each other. We consider ferromagnetic as well as anti-ferromagnetic interactions. The ferromagnetic model exhibits avalanches and non-equilibrium critical behavior. The anti-ferromagnetic model is marked by the absence of these features. The ferromagnetic model is Abelian, and the anti-ferromagnetic model is non-Abelian. Theoretical approaches based on the probabilistic method are discussed in the two cases, and illustrated by deriving some basic results.
MONTE CARLO SIMULATION OF ACTIN FILAMENT BASED CELL MOTILITY
Authors: HERRMANN K. -H. , SATYANARAYANA S. V. M. , SRIDHAR V. , MURTHY K. P. N.
Published: January 2004

Cell motility resulting from actin polymerization is modeled on a two-dimensional square lattice. The treadmilling of actin filaments, formation of lamellipodia, protrusion and motility of the model cell are studied using Monte Carlo simulations. The grid space of the square lattice and the Monte Carlo step are related to length and time scales of the problem. The average velocity computed with this prescription from the simulations shows a remarkable agreement with the experimental velocity of a keratocyte. The model cell captures the essential aspects of treadmilling based motility. The movement of the model cell is diffusive for small times and exhibits a cross over to polymerization driven drift for large times. The studies on the parameter sensitivity of cell velocity indicated that the optimal choice of number of monomers, the number of filaments, the rate of depolymerization and the monomer diffusion leads to large velocities. The cell velocity distribution is found to be Gaussian and is in agreement with some of the experimental work.
FRICTIONAL INDETERMINANCY OF FORCES IN HARD-DISK PACKINGS
Authors: UNGER TAMÁS , KERTÉSZ JÁNOS
Published: January 2004

We study the statical indeterminacy of contact forces in 2D random frictional packings of perfectly rigid disks. Based on contact dynamics simulations we perform a random walk in the force space in order to explore the equilibrium force-states for a fixed packing structure. Our measurement is in agreement with the isostaticity of frictionless hard particles, in that case forces are fully determined. For non-zero friction coefficient the problem gets undetermined, the possible force fluctuations are growing with increasing friction up to a maximum at friction coefficient around 0.1. Further increase of friction reduces the force fluctuations on the average.
IN-PLANE ROUGHNESS OF BRITTLE CRACKS
Authors: BATROUNI G. GEORGE , HANSEN ALEX , SCHMITTBUHL JEAN
Published: January 2004

We review and discuss recent work on the in-plane roughness of slow-propagating brittle mode I fractures.
VENTRICULAR FIBRILLATION IN A SIMPLE EXCITABLE MEDIUM MODEL OF CARDIAC TISSUE
Authors: SHAJAHAN T. K. , SINHA SITABHRA , PANDIT RAHUL
Published: January 2004

Ventricular fibrillation (VF), the major reason behind sudden cardiac death, is turbulent cardiac electrical activity in which rapid, irregular disturbances in spatiotemporal electrical activation of heart make it incapable of any concerted pumping action. We give a brief overview of the simple Panfilov model for ventricular fibrillation, with emphasis on studies that have elucidated the nature of spiral turbulence which is the analog of VF here. The control of such turbulence is briefly touched upon. Preliminary results are presented for the effects of conduction inhomogeneity on spiral breakup, and the transition from functional to anatomical reentry as a function of the size and position of the inhomogeneity.
METAL–INSULATOR TRANSITION IN A QUASI-LOW-DIMENSIONAL SEMICONDUCTOR SYSTEM
Authors: PETER A. JOHN
Published: January 2004

Metal–Insulator transition using exact quasi dielectric functions is investigated for a shallow donor in an isolated well of GaAs/Ga 1-x Al s As superlattice system within the effective mass approximation. Vanishing of the donor ionization energy as a function of well width and the donor concentration suggests that no transition is possible below a well width of 50 Å supporting the scaling theory of localization. The effects of Anderson localization, exchange and correlation in the Hubbard model are included in a simple way. The relationship between the present model and the Mott criterion in terms of Hubbard model is also brought out. The critical concentration is enhanced when a random distribution of impurities is considered. Results are compared with the existing data available and discussed in the light of existing literature.
EFFECT OF TEMPERATURE ON THE BINDING ENERGY OF LOW LYING EXCITED STATES IN A QUANTUM WELL
Authors: NITHIANANTHI P. , JAYAKUMAR K.
Published: January 2004

The temperature dependent binding energy of some low lying excited states for a compositional Quantum Well have been calculated for various impurity locations by extending the investigation of Elabsy.4 It has been observed that the temperature plays an important role in the binding energy of low lying excited states also.
ON A MODEL OF SUPERCONDUCTIVITY REALIZED IN THE METALLIC PHASE OF STRONGLY CORRELATED ELECTRONS REVEALING A FIRST-ORDER PHASE TRANSITION
Authors: GONCZAREK RYSZARD , KRZYZOSIAK MATEUSZ
Published: January 2004

Model of superconductivity in the metallic phase of strongly correlated electrons in a half-filled narrow band forming a paramagnetic spin liquid is presented. A qualitatively new ground state and other eigenstates for the superconducting phase are found. Thermodynamic functions are derived within the Bogolubov method. Analytical formulae for the free energy as well as the gap equation and the equation for the chemical potential are presented. It is shown that the energy gap and the chemical potential are mutually correlated functions which must be simultaneously derived in a self-consistent manner. The gap equation and the equation for the chemical potential are numerically solved. The energy gap is doubly-valued in the subcritical temperature region, however only for the higher values of the gap the superconducting phase is stable. The phase transition between the superconducting and the normal phase is found to be of the first order with a conspicuous discontinuity in the entropy. Moreover it is shown that the derivation of the superconducting specific heat from the thermodynamic potential difference requires to include a chemical potential contribution.
ONE- AND TWO-PARTICLE PHENOMENA IN THE ELECTRONIC LIFETIMES IN METALS: QUASIPARTICLES AND TRANSIENT EXCITONS
Authors: SCHÖNE WOLF-DIETER
Published: January 2004

The experimental and theoretical investigation of the lifetime of excited electrons is of great importance for a variety of different fields in condensed matter physics. In this review two distinct classes of processes are discussed, which determine the lifetime of excited electrons in crystalline systems. One class is single-particle processes, which in many cases is able to describe the decay of excited electrons. For systems with weakly correlated electrons the state-of-the-art method is the solution of the Dyson equation using the GW approximation for the electronic self-energy. If applicable this approach leads to very good results. However, many of the experimental studies about the lifetime of excited electrons have been done using time-resolved two-photon photoemission spectroscopy utilizing ultrashort laser pulses. This technique, applied to materials with localized d electrons, can lead to the creation of bound, excitonic-like states in metals on a very short time scale, which are beyond the physics described in the single-particle approach. In this review the experimental evidence for both mechanisms is given and the theoretical tools to describe them are discussed. Furthermore, theoretical results are presented and compared to experimentally available data.
EXACT AND SELF-CONSISTENT RESULTS IN ONE-DIMENSIONAL REPULSIVE HUBBARD MODEL
Authors: KOCHARIAN ARMEN N. , YANG C. , CHIANG Y. L. , CHOU T. Y.
Published: January 2004

The shortcomings and advantages of the generalized self-consistent field (GSCF) approach, which includes the electron–hole order parameter [Formula: see text] and the average spin s within the one-dimensional repulsive Hubbard model, are analyzed by comparison of the ground state properties with the corresponding Bethe ansatz results in an entire parameter space of interaction strength U/t ≥ 0, magnetic field h ≥ 0 and electron concentration 0 ≤ n ≤ 1. The GSCF spectral characteristics are derived and criteria are found for the stability of incommensurate magnetic phase with the wave number 0 < q < π. The GSCF theory displays a simple relationship for the double occupancy D(+) in terms of n, s and [Formula: see text], where D(+) underestimates electron correlations at weak and intermediate ranges and overestimates correlations at large interaction strengths. Beyond some critical U/t and n≠1 the GSCF D(+) for spatially homogeneous state vanishes, while the exact D for all n at h=0 decreases gradually as U/t increases. At n ≠ 1 the GSCF chemical potential μ(+) overestimates electron correlations everywhere and variation μ(+)versusn displays electron instability toward the phase separation in the vicinity of n=1. Exactly at n=1 the GSCF μ(+)versusU/t always underestimates electron correlation and as U/t → ∞ at h=0 we have μ(+) → 0, while the Bethe ansatz result gives μ → 2t. In the limiting cases U/t → 0 and U/t → ∞ for all h ≥ 0 and 0 ≤ n ≤ 1 the GSCF ground state energy is exact, which is necessary for formulation of converging perturbation procedure about mean field solution in the entire parameter space.
INTENSITY DEPENDENT COUPLING HAMILTONIAN VIA MULTI-PHOTON INTERACTION IN A KERR MEDIUM
Authors: ZAIT R. A.
Published: January 2004

We study the dynamics and quantum characteristics of a single two-level atom interacting with a single mode cavity field undergoing a multi-photon processes in the presence of a nonlinear Kerr-like medium. The wavefunctions of the multi-photon system are obtained when the atom starts in the excited and in the ground state. The atomic inversion, the squeezing of the radiation field and the quasiprobability distribution Q-function of the field are discussed. Numerical results for these characteristics are presented when the atom starts in the excited state and the field mode in a coherent state. The influence of the presence and absence of the number operator and the Kerr medium for the one- and two-photon processes on the evolution of these characteristics are analyzed.
SUBLATTICES OF LATTICES OF ORDER-CONVEX SETS, II.
Authors: SEMENOVA MARINA , WEHRUNG FRIEDRICH
Published: January 2004

For a positive integer n, we denote by SUB (respectively, SUBn) the class of all lattices that can be embedded into the lattice Co(P) of all order-convex subsets of a partially ordered set P (respectively, P of length at most n). We prove the following results:

(1) SUBnis a finitely based variety, for any n≥1.

(2) SUB2is locally finite.

(3) A finite atomistic lattice L without D-cycles belongs to SUB if and only if it belongs to SUB2; this result does not extend to the nonatomistic case.

(4) SUBnis not locally finite for n≥3.
FREE MONOID THEORY: MAXIMALITY AND COMPLETENESS IN ARBITRARY SUBMONOIDS
Authors: NÉRAUD JEAN , SELMI CARLA
Published: January 2004

In this paper, we discuss the different notions of local topological density for subsets of the free monoid A*. We introduce the notion of weak completeness for a set X, relatively to an arbitrary submonoid M of A*.

For the so-called strongly M-thin codes, we establish that weak completeness is equivalent to maximality in M. This constitutes a new generalization of a famous result due to Schützenberger.
ON THE CHECKING OF G-COHERENCE OF CONDITIONAL PROBABILITY BOUNDS
Authors: BIAZZO VERONICA , GILIO ANGELO , SANFILIPPO GIUSEPPE
Published: January 2004

We illustrate an approach to uncertain knowledge based on lower conditional probability bounds. We exploit the coherence principle of de Finetti and a related notion of generalized coherence (g-coherence), which is equivalent to the "avoiding uniform loss" property introduced by Walley for lower and upper probabilities. Based on the additive structure of random gains, we define suitable notions of non relevant gains and of basic sets of variables. Exploiting them, the linear systems in our algorithms can work with reduced sets of variables and/or constraints. In this paper, we illustrate the notions of non relevant gain and of basic set by examining several cases of imprecise assessments defined on families with three conditional events. We adopt a geometrical approach, obtaining some necessary and sufficient conditions for g-coherence. We also propose two algorithms which provide new strategies for reducing the number of constraints and for deciding g-coherence. In this way, we try to overcome the computational difficulties which arise when linear systems become intractable. Finally, we illustrate our methods by giving some examples.
A lower bound for ratio of power means
Authors: Qi Feng , Guo Bai-Ni , Debnath Lokenath
Published: January 2004

Let n and m be natural numbers. Suppose that is an increasing, logarithmically convex, and positive sequence. Denote the power mean Pn(r) for any given positive real number r by . Then Pn(r)/Pn+m(r) ≥ an/an+m. The lower bound is the best possible.
On Gromov′s theorem and L 2‐Hodge decomposition
Authors: Gong Fu-Zhou , Wang Feng-Yu
Published: January 2004

Using a functional inequality, the essential spectrum and eigenvalues are estimated for Laplace‐type operators on Riemannian vector bundles. Consequently, explicit upper bounds are obtained for the dimension of the corresponding L 2‐harmonic sections. In particular, some known results concerning Gromov′s theorem and the L 2‐Hodge decomposition are considerably improved.
Estimates of convolutions of certain number‐theoretic error terms
Authors: Ivić Aleksandar
Published: January 2004

Several estimates for the convolution function and its iterates are obtained when f(x) is a suitable number‐theoretic error term. We deal with the case of the asymptotic formula for (k = 1, 2), the general Dirichlet divisor problem, the problem of nonisomorphic Abelian groups of given order, and the Rankin‐Selberg convolution.
[Retracted] Partial sums of functions of bounded turning
Authors: Jahangiri Jay M. , Farahmand K.
Published: January 2004

We determine conditions under which the partial sums of the Libera integral operator of functions of bounded turning are also of bounded turning.
Thrombin binding to GPIbα induces integrin αIIbβ3 dependent platelet adhesion to fibrin in ex vivo flowing whole blood
Authors: Reigner Sylvie C. , Steiner Beat , Dubois Christophe , Riederer Markus
Published: January 2004

We have investigated the role of the thrombin/GPIbα interaction in the adhesion of platelets to fibrin in a whole blood ex vivo perfusion model at a shear rate of 280 s-1. Blood was perfused through parallel-plate chambers containing coverslips coated with cells expressing tissue factor, leading to the generation of thrombin and thus, deposition of fibrin onto the exposed cells. Adhesion of platelets to fibrin and thrombus growth were analyzed. Interestingly, when GPIbα was removed from the platelet surface by action of mocarhagin, platelet adhesion on fibrin was inhibited. Furthermore, a monoclonal antibody, VM16d, directed against the thrombin binding site on GPIbα also inhibited platelet adhesion on fibrin, showing the importance of the thrombin/GPIbα interaction. We then looked at the involvement of αIIbβ3 and showed that platelet adhesion and thrombus growth on fibrin were inhibited by the dodecapeptide, whereas lamifiban only inhibited the growth of the platelet thrombus. These results indicated that binding of thrombin to GPIbα induced an intracellular signaling leading to the interaction of the platelet integrin αIIbβ3 with the fibrindodecapeptide sequence.
Coagulopathy of sepsis
Authors: Dempfle Carl-Erik
Published: January 2004

Disseminated intravascular coagulation (DIC) is a common phenomenon in patients with sepsis, but the clinical implications of this condition are not clear. Clinical trials with coagulation inhibitors have failed to show a significant benefit concerning survival. DIC is primarily a laboratory diagnosis, based on the combination of elevated fibrin-related markers (FRM), with decreased procoagulant factors and platelets. Non-overt DIC is observed in most patients with sepsis, whereas overt DIC is less frequent. Patients with overt DIC may display consumption coagulopathy and purpura fulminans. Consumption coagulopathy is a bleeding disorder caused by low levels of platelets and procoagulant factors associated with massive coagulation activation. Purpura fulminans is caused by widespread microvascular thrombosis, resulting in tissue necrosis. Treatment with drotrecogin alfa (activated) improves survival and other outcome parameters in severe sepsis, including a subgroup of patients fulfilling the laboratory criteria of overt DIC. No randomized trials demonstrating effective therapies in consumption coagulopathy have been published. Bleeding patients with consumption coagulopathy are most frequently treated with platelet transfusions and various plasma products including fresh frozen plasma and coagulation factor concentrates. Based on case reports, treatment with drotrecogin alfa (activated) or substitution of protein C have been recommended for adjuvant treatment of sepsis-related purpura fulminans.
Relationships between plasma adiponectin and blood cells, hepatopancreatic enzymes in women
Authors: Namioka Katsuhiko , Katayose Shinji , Matsubara Miyao
Published: January 2004

Adiponectin, which is secreted specifically from adipocyte, is thought to play a key role in the metabolic syndrome. We studied the associations of plasma adiponectin concentrations with blood cells and hepatopancreatic enzymes in 339 women aged 54.0 ± 0.8 (mean ± SE) years. Plasma adiponectin before and after adjustment for body composition or calculated insulin resistance increased in slight anemic women (372.6 ± 2.6 ×104/mm3) compared with non-anemic subjects (471.1 ± 1.7) (all p < 0.0001), and were inversely associated with red blood cells (RBC), hemoglobin, hematocrit, white blood cells and platelet values (p < 0.0001 ∼ 0.02), independent of age, diastolic blood pressure, body mass index, serum triglyceride, insulin resistance or blood urea nitrogen. Age and adiponectin/body fat mass (%) were negative, and blood pressure and insulin resistance were positive significant independent determinants of RBC in stepwise regression analysis. Moreover, adiponectin before and after adjustment were inversely associated with serum ALAT,γGTP and ChE, and positively with amylase levels (p < 0.0001 ∼ 0.02). These results indicate the possibility that increased adiponectin may contribute to the suppressive bone marrow function in vivo. Combined with the leptin’s data, adipocyte derived proteins were related to the hematopoiesis, therefore it has shown the possible existence of adipose tissue/ bone marrow function linkage more clearly. Furthermore, hepatopancreatic enzyme associations with this protein may indicate the possibility that adiponectin will regulate the hepatopancreatic function in health and disease.
Plasma MMP–2 and MMP–9 and their inhibitors TIMP-1 and TIMP-2 during human orthotopic liver transplantation
Authors: Kuyvenhoven Johan , Molenaar Quintus , Veldman Marietta , Palareti Gualtiero , Legnani Cristina , Moolenburgh Sanne , Terpstra Onno , Lamers Cornelis , van Hoek Bart , Porte Robert , Verspaget Hein
Published: January 2004

Uncontrolled activation of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation, yet little is known about the activation of MMPs during orthotopic liver transplantation (OLT). OLT is associated with increased fibrinolytic activity due to elevated plasmin generation. The serine-protease plasmin not only causes degradation of fibrin clots but is also thought, amongst others, to play a role in the activation of some matrix metalloproteinases. We therefore studied the evolution of MMP-2 and -9 plasma concentrations during OLT and the effect of serine-protease inhibition by aprotinin on the level and activation of these MMPs. In a group of 24 patients who participated in a randomized, double-blind, placebo-controlled study we determined serial MMP-2 and MMP-9 plasma levels during transplantation using ELISA (total MMP), activity assays (activatable MMP) and zymography. In addition, the MMP-inhibitors TIMP-1 and TIMP-2 were assessed by ELISA. The putative regulating factors tumor necrosis factor alpha (TNF-α) and tissue-type plasminogen activator (t-PA) were assessed as well. Patients were administered high-dose aprotinin, regular-dose aprotinin or placebo during surgery. Plasma TIMP-1, TIMP-2 and MMP-2 level gradually decreased during transplantation. Approximately twothirds of total MMP-2 appeared to be in its activatable proMMP form. No release of MMP-2 from the graft could be detected. In contrast, plasma levels of MMP-9 increased sharply during the anhepatic and postreperfusion periods. Peak MMP-9 levels of about eight times above baseline were found at 30 minutes after reperfusion. Most MMP-9 appeared to be in its active/inhibitorcomplexed form. No significant differences were observed between the three treatment groups. However, in patients with more severe ischemia/reperfusion (I/R) injury the MMP-9 concentration, particularly of the active/inhibitor-complexed form, remained high at 120 minutes postreperfusion compared to patients with no or mild I/R injury. The decrease in plasma levels of MMP-2,TIMP-1 and TIMP-2 during OLT occurred irrespective of the severity of the I/R injury. There was a significant correlation between MMP-9 and t-PA levels, but not with TNF-α. In conclusion, OLT is associated with a sharp increase of MMP-9 during the anhepatic and postreperfusion periods, which coincided with the changes in t-PA. MMP-2, TIMP-1 and TIMP-2 gradually decreased during OLT. The composition of these MMPs was not altered by the use of aprotinin, suggesting that serine–protease/plasmin-independent pathways are responsible for MMP regulation during OLT. In addition, only MMP-9 seems to be involved in I/R injury during human liver transplantation.
Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus
Authors: Morel Olivier , Hugel Bénédicte , Jesel Laurence , Lanza François , Douchet Marie-Pierre , Zupan Michel , Chauvin Michel , Cazenave Jean-Pierre , Freyssinet Jean-Marie , Toti Florence
Published: January 2004

During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardiovascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 ± 4.8 vs. 12.3 ± 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.
Activated protein C generation is greatly decreased in plasma from newborns compared to adults in the presence or absence of endothelium
Authors: Patel Sanjay , Male Christoph , Berry Leslie , Mitchell Lesley , Chan Anthony
Published: January 2004

Activated protein C (APC) generation strongly affects sepsis and thrombosis by inhibition of thrombin generation. However, it is unclear if there are age-related differences in effectiveness of protein C (PC). We studied age effects on plasma APC generation ± endothelium. Defibrinated (Ancrod) plasma (from adults or newborns (umbilical cord)) was recalcified with buffer containing tissue factor ± thrombomodulin (TM) on either plastic or endothelium (HUVEC) at 37oC. Timed subsamples of reaction mixture were taken into either heparin-EDTA or FFRCMK-EDTA solutions and analyzed for APC-PC inhibitor (APC-PCI) or APC-α1antitrypsin (APC-α1AT) by ELISAs. Since heparin converts free APC to APC-PCI, the difference in APCPCI measured in heparin-EDTA and FFRCMK-EDTA samples was equal to free active APC. APC-α2macroglobulin (APC-α2M) was measured as remaining chromogenic activity in heparin-EDTA. Free APC, APC-PCI and APC-α1AT were decreased in newborn compared to adult plasma on plastic. However, APC-α2M made up a larger fraction of inhibitor complexes in newborn plasma. On endothelium, significantly more APC, APC-PCI and APC-α1AT were generated in either plasma compared to that on plastic with excess added TM. APC, APC-PCI and APC-α1AT were also reduced and total APC-α2M increased in newborn plasma on HUVEC. Addition of PC to newborn plasma gave APC generation similar to adult plasma. Thus, free APC, APC-PCI and APC-α1AT generation is reduced in newborn compared to adult plasma with or without endothelium, likely due to reduced plasma PC levels. Endothelium enhances APC generation, regardless of plasma type, possibly because of cell surface factors such as TM, phospholipid and endothelial PC receptor.
Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation
Authors: Egberg Nils , Nordin Gunnar , Stigendal Lennart , Fagerberg Inger , Lindahl Tomas , Hillarp Andreas
Published: January 2004

In 1999, a simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced by a working group of the organisation for national quality assurance in laboratory medicine in Sweden. The new protocol allowed local calibration by means of only two lyophilised national plasma calibrators and expression of results as an international normalized ratio (INR). This is our report of a three-year follow-up involving the analysis of data from all laboratories, in hospitals (n=88 in 2002) and primary health care units (n=246 in 2002) that perform the Owren PT assay in Sweden. The interlaboratory variation was significantly improved after the introduction of the new calibration procedure. For the larger hospital-based laboratories, the mean coefficient of variation (CV) was reduced from 7.9% to 5.2% (p<0.0001) when analysing test materials with INR range 2-4. In the higher INR range (>4), the CV was reduced even further, from 10.4% to 6.8% (p<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.2% to 5.7% in the INR range 2-4 (p<0.0001). At the INR range >4, the CV was reduced from 9.5% to 7.8%. The intralaboratory variation was also improved for both types of laboratory categories. This study shows an improved precision, with CV less than 6% at the therapeutic INR range, for both hospital-based laboratories and smaller laboratories in the primary health care system. The results indicate that the Owren PT assay is well suited for local INR calibration employing only two calibrant plasmas in a simplified procedure.
Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study
Authors: Braam Lavienja , Hoeks Arnold , Brouns Fred , Hamulyák Karly , Gerichhausen Monique , Vermeer Cees
Published: January 2004

Matrix-Gla Protein (MGP) is a strong inhibitor of vascular calcification, the expression of which is vitamin D dependent. MGP contains five γ-carboxyglutamic acid (Gla)-residues which are formed in a vitamin K-dependent carboxylation step and which are essential for its function. Hence vascular vitamin K-deficiency will result in undercarboxylated, inactive MGP which is a potential risk factor for calcification. In the present study we describe the effects of vitamin K1 and D supplementation on vascular properties in postmenopausal women. In a randomized placebo-controlled intervention study, 181 postmenopausal women were given either a placebo or a supplement containing minerals and vitamin D (MD-group), or the same supplement with vitamin K1 (MDK-group). 150 participants completed the study and analysis was performed on 108 participants. At baseline and after three years, vessel wall characteristics, including compliance coefficient (CC), distensibility coefficient (DC), intima-media thickness (IMT) and the Young’s Modulus (E) were measured to assess the effect of the supplements on the change of these parameters. The results showed that the elastic properties of the common carotid artery in the MDK-group remained unchanged over the three-year period, but decreased in the MDand placebo-group. Comparing the MDKand placebo-group, there were significant differences in decrease of DC (8.8%; p<0.05), CC (8.6%; p<0.05), and in increase of PP (6.3%; p<0.05) and E (13.2%, p<0.01).There were no significant differences between the MD-group and placebo. No significant differences were observed in the change of IMT between the three groups. It is concluded that a supplement containing vitamins K1 and D has a beneficial effect on the elastic properties of the arterial vessel wall.
Effect of age on the performance of single detector helical computed tomography in suspected pulmonary embolism
Authors: Bounameaux Henri , Perrier Arnaud , Righini Marc
Published: January 2004

The prevalence of pulmonary embolism increases with age, but reduces the diagnostic yield of ventilation-perfusion lung scan age. Helical computed tomography (hCT) is widely used to diagnose pulmonary embolism, and should be less susceptible to the influence of age. We studied the influence of age on the performance of hCT to verify that hypothesis. We analyzed a database of 299 consecutive outpatients suspected of pulmonary embolism, in whom pulmonary embolism was diagnosed according to accepted criteria, and who were all submitted to a helical CT. We divided the patient population into tertiles, corresponding to the following age categories: less than 59 years (group 1), 60 to 75 years (group 2), and over 75 years (group 3). Sensitivity and specificity of hCT were calculated in each age category. Overall sensitivity was 70% (95% CI: 62 to 78) and specificity was 91% (95% CI: 86 to 95). Sensitivity was 81% (95% CI: 64 to 93) in group 1, 63% (95% CI: 46 to 78) in group 2, and 67 % (95% CI: 52 to 80) in group 3.The corresponding values for specificity were 92% (95% CI: 82 to 97) in group 1, 86% (95% CI: 75 to 94) in group 2 and 96% (95% CI: 87 to 100) in group 3. Positive predictive values ranged from 75% to 94% and negative predictive values from 77% to 94%. Our data suggest that age does not have a marked influence on the diagnostic performances of hCT in clinically suspected pulmonary embolism.
Epitope mapping of polyclonal clotting factor VIII-inhibitory antibodies using phage display
Authors: Mühle Christiane , Schulz-Drost Stefan , Khrenov Alexey , Saenko Evgueni , Klinge Jens , Schneider Holm
Published: January 2004

Clotting factor VIII (fVIII)-inhibitory antibodies represent a major problem in the treatment of haemophilia A. To understand the inactivation mechanisms and to pave the way towards modifications of recombinant clotting factors that reduce their immunogenicity, the exact localization of immunodominant epitopes is required. Here, a random peptide phage display library was employed to identify epitopes of polyclonal fVIII antibodies isolated from patient’s plasma by affinity chromatography. FVIIIbinding specificity and inhibitory activity of the isolated fVIII antibodies were confirmed by ELISA and Bethesda assays. Phage selection on the individual samples yielded several phages which were displaced from binding to the respective antibody preparation by fVIII. Their homology with amino acid motifs of human fVIII and immunoprecipitation results with radioactively labelled fVIII fragments suggested putative epitopes in the A1, A2 and C1 domains of fVIII for one and in the C2 domain for another patient. Synthetic peptides corresponding to the A2, C1 and C2 domain epitopes blocked antibody binding to fVIII and partially neutralized the inhibitory activity of the respective plasma in Bethesda assays. These results provide the proof of principle that random peptide libraries can be used for the mapping of epitopes in a polyclonal antibody preparation.
Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients?
Authors: Paltiel Ora , Bursztyn Michael , Gatt Moshe
Published: January 2004

Prolonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patient’s mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85 ± 8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p = 0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.
Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome
Authors: Camoin-Jau Laurence , Sabatier Florence , Arnoux Dominique , Anfosso Francine , Bardin Nathalie , Veit Véronique , Combes Valéry , Gentile Stéphanie , Moal Valérie , Sanmarco Marielle , Sampol José , Dignat-George Françoise
Published: January 2004

The antiphospholipid syndrome (APS) refers to persistent antiphospholipid antibodies (aPL) associated with thrombotic and/or obstetrical complications. The endothelial cell is a target of aPL which can induce a procoagulant and proinflammatory endothelial phenotype, as reported both in vivo and in vitro. Microparticle production is a hallmark of cell activation. In the present study, the presence of endothelial microparticles (EMP) in the plasma of APS patients was investigated. To determine if there is a correlation with certain biological and clinical features, EMP levels were measured in thrombosis-free patients with systemic lupus erythematosus (SLE) patients, with and without aPL, in patients with non aPL-related thrombosis, as well as in healthy controls. Compared to healthy subjects, elevated plasma levels of EMP were found in patients with APS and in SLE patients with aPL, but not in SLE patients without aPL or in non aPL-related thrombosis. EMP levels were also associated with Lupus Anticoagulant (LA) detected by a positive Dilute Russell’s Viper Venom time (DRVVT). In parallel, we analyzed the capacity of these plasma to induce vesiculation of cultured endothelial cells. We demonstrated an increase of EMP generated in response to plasma from patients with autoimmune diseases. Interestingly, only APS plasma induced the release of EMP with procoagulant activity. These ex vivo and in vitro observations indicate that generation of EMP in APS and SLE patients results from an autoimmune process involving aPL. Production of procoagulant microparticles in APS patients may represent a new pathogenic mechanism for the thrombotic complications of this disease.
Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism
Authors: Zanon Ezio , Saggiorato Graziella , Ramon Roberto , Girolami Antonio , Pagnan Antonio , Prandoni Paolo
Published: January 2004

The role of antiprothrombin (aPT) antibodies in the development of venous thromboembolism (VTE) is still uncertain. The aim of this study was to evaluate the potential role of aPT antibodies in the development of recurrent thromboembolism. Out of 236 consecutive symptomatic patients with an episode of acute VTE, antiphospholipid antibodies were found in 85 (36.0%), of whom 24 were carriers of aPT antibodies (10.2% of the entire cohort). A history of previous thromboembolism was identified in 56 patients (23.7%). The prevalence of previous thromboembolism was significantly higher in carriers than in non-carriers of antiphospholipid antibodies (OR=2.4; 95% CI, 1.3 to 4.4). Of the 24 patients with aPT antibodies, 12 had a history of previous thromboembolism. In a multivariate logistic regression analysis, in which the other categories of antiphospholipid antibodies were taken into account, as well as the patient’s age, sex, and the modality of clinical presentation, it was found that the presence of aPT antibodies was significantly associated with the prevalence of prior thromboembolism (OR=3.3; 95% CI, 1.3 to 8.6). Since aPT antibodies are more commonly identifiable in patients with multiple thrombotic episodes, they are a likely risk factor for recurrent thromboembolism.
Enhancement of endogenous fibrinolysis does not reduce local fibrin deposition, but modulates inflammation upon intestinal ischemia and reperfusion
Authors: Levi Marcel , van Vliet Arlène , Declerck Paul , Maas Adrie , van Gulik Thomas , Schoots Ivo
Published: January 2004

This study investigated the contribution of endogenous suppression of fibrinolysis and increased fibrin deposition to intestinal dysfunction and injury in a rat model of intestinal ischemia/ reperfusion (I/R), as fibrinolytic inhibition may lead to thrombotic obstructions that compromise microcirculation and promote intestinal injury. Circulatory fibrinolysis was enhanced by intravenous administration of recombinant tissue plasminogen activator (rt-PA) or by inhibition of PAI-1 by administration of MA-33H1F7. Coagulation and fibrinolysis parameters obtained from portal blood were correlated to fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance) and intestinal injury (histological evaluation by Park/Chiu score).

Enhanced circulatory fibrinolytic activity, as evidenced by increased portal plasma plasminogen activator activity, elevated fibrin degradation products and decreased levels of PAI-1, did not reduce mucosal fibrin deposition and microthrombosis in postischemic intestinal tissue. Furthermore, rt-PA or anti-PAI-1 antibody administration did not attenuate I/R-induced intestinal injury or dysfunction, as demonstrated by intestinal histopathology scores of 4.8±0.2 and 4.7±0.3 (control I/R group 4.7±0.2) and glucose clearances of 47±6 and 46±9 µL/min · g (control I/R group 30±8 µL/min · g) after 40 minutes of intestinal ischemia and 3 hours of reperfusion, respectively. However, both interventions resulted in decreased levels of interleukin-6, which may indicate fibrin-induced modulation of inflammation. Attempts to enhance the fibrinolytic activity (either by rt-PA or by anti-PAI-1 administration), indicated by increased portal plasma levels of released FDP, failed to decrease mucosal fibrin deposition and to attenuate intestinal I/R injury. Based on our observations and previous reports, the contribution of suppressed endogenous fibrinolysis to microcirculatory fibrin deposition and I/R-injury may be of limited importance.