bluuebunny/crossref_metadata_2025 huggingface dataset:
CANNULATION PRACTICE PATTERNS IN HAEMODIALYSIS VASCULAR ACCESS: PREDICTORS FOR UNSUCCESSFUL CANNULATION
Authors: Van Loon Magda M. , Kessel Alphons G.H. , Van Der Sande Frank M. , Tordoir Jan H.M.
Published: May 2009

Background: Little is known about the relationship of cannulation practices in dialysis facilities with the frequency of failed cannulations, complications and subsequent vascular access (VA) failure. Methods: In an observational study the incidence of mis‐cannulations and related complications were observed. Patient characteristics, comorbidities and VA characteristics like type of VA were correlated with occurrence of cannulation‐related complications. In addition, the cannulation technique and practice patterns like needle direction, tourniquet use and years of experience of dialysis nurses were registered. Results: During the study period, 37% of patients with autogenous arteriovenous fistulae (AVF), and 19% of patients with arteriovenous grafts (AVG) had more than 10 miscannulations. Cannulation‐induced haematoma resulted into single‐needle (SN) and catheter dialysis in 40% of the patients. The use of central venous catheters (CVC) and SN dialysis were significant predictors of VA failure (p <0.0001). Conclusion: This study demonstrated a high incidence of unsuccessful cannulation procedures and cannulation‐related complications necessitating catheter and SN dialysis. The type and location of the VA is significantly related to occurrence of unsuccessful and complicated cannulation.
PATIENTS’ EXPERIENCE OF TRANSITION ONTO HAEMODIALYSIS: A QUALITATIVE STUDY
Authors: Mitchell Annie , Farrand Paul , James Hayley , Luke Rob , Purtell Rachel , Wyatt Katrina
Published: May 2009

Transition onto haemodialysis is a time of increased psychosocial difficulty, yet, many renal patients exhibit personal resilience in continuing to lead productive lives. Using a positive psychological methodology, this qualitative study aims to identify factors identified by patients as helpful in the transition onto haemodialysis. Semi‐structured interviews were undertaken with 10 patients within six months of starting haemodialysis. Interpretive content analysis identified three main themes (each with subthemes) in patients’ accounts—preparation, cognitive style and social support. Limited differences arose between patients who underwent a gradual versus acute transition onto haemodialysis. Themes are discussed with reference to implications for practice development.
COMPARISON OF INTRAVENOUS IRON SUCROSE VERSUS LOW‐MOLECULAR‐WEIGHT IRON DEXTRAN IN CHRONIC KIDNEY DISEASE
Authors: Sinha Smeeta , Chiu Diana Y.Y. , Peebles George , Kolakkat Shabeer , Lamerton Elizabeth , Fenwick Sean , Kalra Philip A.
Published: May 2009

Background: Low‐molecular‐weight iron dextran (CosmoFer®) is the only form of parenteral iron that can be administered as a total dose infusion (TDI) in the United Kingdom (UK). This study aimed to evaluate the safety and efficacy of TDI CosmoFer in comparison to intravenous iron sucrose infusion (Venofer®) in patients with chronic kidney disease (CKD).

Methods and Results: A retrospective study of outpatients with CKD undergoing intravenous TDI CosmoFer or Venofer infusion was conducted at Salford Royal Hospital and Sunderland Royal Hospital. A total of 979 doses of CosmoFer and 504 doses of Venofer were administered. There were three minor adverse events in patients receiving CosmoFer compared with one minor event in a Venofer treated patient. There were no anaphylactoid‐type reactions in either group. Serum haemoglobin, ferritin and transferrin saturation (TSAT) improved significantly 4–6 months postinfusion in both treatment groups.

Conclusion: TDI CosmoFer is an efficacious method of replenishing iron stores in CKD patients in an outpatient setting. Furthermore, TDI CosmoFer is safe and not associated with an increase in adverse events compared to Venofer.
Development of a hepatitis C virus relapse model using genome‐length hepatitis C virus ribonucleic acid‐harboring cells possessing the interferon‐α‐resistance phenotype
Authors: Kawai Yoshinari , Ikeda Masanori , Abe Ken‐ichi , Yano Masahiko , Ariumi Yasuo , Dansako Hiromichi , Yamamoto Kazuhide , Kato Nobuyuki
Published: May 2009

Aim:  The cure rate of current interferon (IFN) therapy is limited to approximately 50% and most of the relapses after therapy are caused by genotype‐1. To develop a relapse model in cell culture, we attempted to obtain genome‐length hepatitis C virus ribonucleic acid (HCV RNA) harboring cells possessing the IFN‐α‐resistance phenotype from previously established OR6 cells, which enabled the luciferase reporter assay for monitoring of HCV RNA replication.

Methods:  The IFN‐α‐resistant HCV RNA‐harboring cells and control cells were obtained by the treatment of OR6 cells with and without IFN‐α, respectively. Then, we examined the relapse of HCV in IFN‐α‐resistant HCV RNA‐harboring cells.

Results:  Only type I IFN (α and β) showed significantly different anti‐HCV activity between IFN‐α‐resistant HCV RNA‐harboring cells and control cells. There was no significant difference in the anti‐HCV activity of IFN‐γ, fluvastatin, or cyclosporine A between the two types of cells. Furthermore, we showed that fluvastatin or cyclosporine A in combination with IFN‐α could prevent the relapse after therapy in the IFN‐α‐resistant HCV RNA‐harboring cells.

Conclusion:  We developed a HCV relapse model in cell culture using IFN‐α‐resistant HCV RNA‐harboring cells. Thus anti‐HCV reagents, which have a mechanism different from IFN‐α, were shown to be useful for preventing a relapse of IFN‐α‐resistant HCV.
Ursodeoxycholic acid in primary sclerosing cholangitis: meta‐analysis of randomized controlled trials
Authors: Shi Jian , Li Zhi , Zeng Xin , Lin Yong , Xie Wei‐Fen
Published: May 2009

Aims:  The effect of ursodeoxycholic acid (UDCA) treatment on survival and liver histological progression of primary sclerosing cholangitis (PSC) remains uncertain. The aim of the present study was to evaluate the effect and safety of UDCA in PSC.

Methods:  Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science and PubMed (updated to January 2009) and manual bibliographical searches were carried out. A meta‐analysis of all randomized controlled trials (RCT) comparing UDCA with placebo or no treatment was carried out.

Results:  Eight RCT including 465 patients were assessed. UDCA could significantly improve liver biochemistry, but had no effect on pruritus and fatigue. Meta‐analysis of the included RCT showed UDCA had no significant effect on the incidence of death, liver transplantation, and death and/or liver transplantation. However, a significant difference for the incidence of histological improvement was found between the two groups (odds ratio [OR], 9.19; 95% CI: 0.98, 86.15; P = 0.05). Meta‐analysis also indicated a reduction trend of histological deterioration and an improvement trend of cholangiographic changes. These trends were constant in the sensitivity analyses.

Conclusion:  The meta‐analysis found that UDCA can improve liver biochemistry and there is a trend towards improvement in liver histology and cholangiography, but has no effect on survival free of transplantation.
The Social Dimension of Security: Exploring how Surveillance Systems Relate to Interior Design
Authors: Hadjiyanni Tasoulla , Kwon Jain
Published: May 2009

Recently, security issues have been dominating the headlines and policy makers’ lists of promises. Although the notion of security has long been integral to interior design, the current reliance of security measures on surveillance systems that use cameras and video monitors warrants revisiting the role of interior designers. With an overview of the literature on how electronic surveillance has been conceived, perceived, and practiced, this paper aims to set the stage for a dialogue about the opportunities that arise through greater involvement from interior designers.

The analysis points to a disconnect between the systems’ application and the fusion of the physical, social, and technological dimensions of electronic surveillance into a holistic scheme. Current debates raise concerns over its aesthetic integration into the overall building design as well as its associations with feelings of fear and control, loss of privacy, discrimination, inequality, and cultural/gender insensitivity.

Directions from academicians, designers, artists, and educators help frame the paper's thesis that electronic surveillance can act as a connecting mechanism that connects people to people as well as people to the environment. Pedagogical implications of this premise suggest that by including the term “surveillance” in the terminology used in the interior design field and positioning security and surveillance in the conceptual stages of the design process, the potential for creative solutions and opportunities to challenge perceptions of fear and threat are increased.
Greater Transportation Energy and GHG Offsets from Bioelectricity Than Ethanol
Authors: Campbell J. E. , Lobell D. B. , Field C. B.
Published: May 2009

Future Fuels

In the scramble to develop more environmentally friendly transportation methods, a wide range of questions must be answered, including how automobiles may best be powered. Biomass might be an important source for that power, either to generate electricity for electric vehicles, or to make ethanol for combustion vehicles.

Campbell
et al.

(p. 1055; published online 7 May; see the Policy Forum by

Ohlrogge
et al.

) examined each approach's demands on land-use, using a lifecycle assessment model, for a range of energy feedstocks, conversion methods, and vehicle types. In nearly all cases, bioelectricity would have a significantly higher net transportation efficiency per area of land used than bioethanol, owing to the greater efficiency of electric engines. Furthermore, bioelectricity would result in a smaller CO
2
burden. Thus, bioelectricity could represent an important bridge to more advanced transportation technologies with less environmental impact.
Recruitment of an Area Involved in Eye Movements During Mental Arithmetic
Authors: Knops André , Thirion Bertrand , Hubbard Edward M. , Michel Vincent , Dehaene Stanislas
Published: May 2009

Addition to the Right, Subtraction to the Left

High-level cognitive achievements, such as writing and mathematics, have appeared relatively recently in the evolutionary record in comparison to low-level skills, such as the perception of bright-dark boundaries. The latter have been demonstrated to arise from the coding properties of neurons in visual cortical centers, but what do the former map onto?

Knops
et al.

(p.
1583
, published online 7 May) provide evidence that addition and subtraction are encoded within the same cortical region that is responsible for eye movements to the right and left, such that the neural activity associated with addition could be distinguished from that associated with subtraction by a computational classifier trained to discriminate between rightward and leftward eye movements.
IL-21 Is Required to Control Chronic Viral Infection
Authors: Elsaesser Heidi , Sauer Karsten , Brooks David G.
Published: May 2009

Controlling Chronic Viral Infections

Chronic viral infections such as HIV and hepatitis B and C viruses are major public health concerns. T cell—mediated immune responses are critical for controlling viral infections. In contrast to acute infections, chronic viral infections are characterized by “exhausted” cytotoxic CD8
+
T cells, cells which exhibit reduced proliferative capacity, cytokine secretion, and cytotoxicity. Treatments that reverse exhaustion result in increased viral control. Despite their exhaustion, these CD8
+
T cells eventually help to control chronic infections by killing virally infected cells, and require CD4
+
T cell help to do so. How do CD4
+
T cells provide help to CD8
+
T cells during chronic infection (see the Perspective by

Johnson and Jameson

)?

Elsaesser
et al.

(p.
1569
, published online 7 May),

Yi
et al.

(p.
1572
, published online 14 May), and

Fröhlich
et al.

(p.
1576
, published online 28 May) now show that the cytokine, interleukin-21 (IL-21), known to be critical for the differentiation of certain CD4
+
T cell effector subsets, is an essential factor produced by CD4
+
T cells that helps CD8
+
T cells to control chronic lymphocytic choriomeningitis virus infection in mice. Acute and chronic infections resulted in differing amounts of IL-21 production by virus-specific CD4
+
T cells. CD8
+
T cells required IL-21 directly, and when CD8
+
T cells were unable to signal through IL-21 or IL-21 was not available, they were reduced in number, exhibited a more exhausted phenotype, and were not able to control the virus. In contrast, the absence of IL-21–dependent signaling did not affect primary CD8
+
T cell responses to acute infection or responses to a viral rechallenge, suggesting that differentiation of memory CD8
+
T cells is independent of IL-21.
YANG–MILLS EQUATION FOR STABLE HIGGS SHEAVES
Authors: BISWAS INDRANIL , SCHUMACHER GEORG
Published: May 2009

We establish a Kobayashi–Hitchin correspondence for the stable Higgs sheaves on a compact Kähler manifold. Using it, we also obtain a Kobayashi–Hitchin correspondence for the stable Higgs G-sheaves, where G is any complex reductive linear algebraic group.
ON QUOTIENT CURVES OF THE FERMAT CURVE OF DEGREE TWELVE ATTAINING THE SERRE BOUND
Authors: KAWAKITA MOTOKO QIU
Published: May 2009

We find explicitly new algebraic curves of genera three, four and ten attaining the Serre bound over prime fields, where we also obtain the conditions on the order of the finite field on which such an algebraic curve attains the Serre bound. Moreover, we show that if a standard conjecture of primes is true, then there are infinitely many primes satisfy the conditions.
ON THE GEOMETRY OF $\overline{S}_2$
Authors: BINI GILBERTO , FONTANARI CLAUDIO
Published: May 2009

We investigate topological properties of the moduli space of spin structures over genus two curves. In particular, we provide a combinatorial description of this space and give a presentation of the (rational) cohomology ring via generators and relations.
TOPOLOGICAL PROPERTIES OF THE CONTACT NETWORK OF GRANULAR MATERIALS
Authors: ARÉVALO ROBERTO , ZURIGUEL IKER , MAZA DIEGO
Published: May 2009

The force networks of different granular ensembles are defined and their topological properties studied using the tools of complex networks. In particular, for each set of grains compressed in a square box, a force threshold is introduced that determines which contacts conform the network. Hence, the topological characteristics of the network are analyzed as a function of this parameter. The characterization of the structural features thus obtained, may be useful in the understanding of the macroscopic physical behavior exhibited by this class of media.
A NODE-BASED MULTISCALE VULNERABILITY OF COMPLEX NETWORKS
Authors: CRIADO R. , PELLO J. , ROMANCE M. , VELA-PÉREZ M.
Published: May 2009

A novel node-based approach to quantify the vulnerability of a complex network is presented. The proposed measure represents a multiscale evaluation of vulnerability closely related to the edge multiscale vulnerability. In fact, a linear relationship between the edge multiscale vulnerability and the node multiscale vulnerability is stated for p = 1. Upper and lower bounds are established for other values of p. This mathematical framework is subsequently used to obtain some interesting results about the Madrid underground network.
ENHANCING NETWORK SYNCHRONIZATION BY SPARSE REPULSIVE COUPLINGS
Authors: ALMENDRAL J. A. , LEYVA I. , SENDIÑA-NADAL I.
Published: May 2009

In a small-world network of mainly attractively coupled nonidentical neurons, we show that a small fraction of phase-repulsive couplings is able to strongly improve synchronization for certain values of the link strength, and long-range connection probability. By means of a spectral analysis we relate the observed dynamical behavior with the structural properties of the network.
SPATIOTEMPORAL COHERENCE RESONANCE IN A MAP LATTICE
Authors: SUN XIAOJUAN , LU QISHAO , KURTHS JÜRGEN , WANG QINGYUN
Published: May 2009

We study the effects of parametric noise on a lattice network, which is locally modeled by a two-dimensional Rulkov map. We conclude that at some intermediate noise intensity, parametric noise can induce ordered circular patterns, which indicates the appearance of spatiotemporal coherence resonance in the studied lattice. With the observation of coherence-like manner in linear spatial cross-correlation, the coherence phenomena can be analyzed quantitatively.
IDENTIFYING DISTINCT STOCHASTIC DYNAMICS FROM CHAOS: A STUDY ON MULTIMODAL NEURAL FIRING PATTERNS
Authors: YANG MINGHAO , LIU ZHIQIANG , LI LI , XU YULIN , LIU HONGJV , GU HUAGUANG , REN WEI
Published: May 2009

Some chaotic and a series of stochastic neural firings are multimodal. Stochastic multimodal firing patterns are of special importance because they indicate a possible utility of noise. A number of previous studies confused the dynamics of chaotic and stochastic multimodal firing patterns. The confusion resulted partly from inappropriate interpretations of estimations of nonlinear time series measures. With deliberately chosen examples the present paper introduces strategies and methods of identification of stochastic firing patterns from chaotic ones. Aided by theoretical simulation we show that the stochastic multimodal firing patterns result from the effects of noise on neuronal systems near to a bifurcation between two simpler attractors, such as a point attractor and a limit cycle attractor or two limit cycle attractors. In contrast, the multimodal chaotic firing trains are generated by the dynamics of a specific strange attractor. Three systems were carefully chosen to elucidate these two mechanisms. An experimental neural pacemaker model and the Chay mathematical model were used to show the stochastic dynamics, while the deterministic Wang model was used to show the deterministic dynamics. The usage and interpretation of nonlinear time series measures were systematically tested by applying them to firing trains generated by the three systems. We successfully identified the distinct differences between stochastic and chaotic multimodal firing patterns and showed the dynamics underlying two categories of stochastic firing patterns. The first category results from the effects of noise on the neuronal system near a Hopf bifurcation. The second category results from the effects of noise on the period-adding bifurcation between two limit cycles. Although direct application of nonlinear measures to interspike interval series of these firing trains misleadingly implies chaotic properties, definition of eigen events based on more appropriate judgments of the underlying dynamics leads to accurate identifications of the stochastic properties.
FOLLOWING A SADDLE-NODE OF PERIODIC ORBITS' BIFURCATION CURVE IN CHUA'S CIRCUIT
Authors: FREIRE E. , PONCE E. , ROS J.
Published: May 2009

Starting from previous analytical results assuring the existence of a saddle-node bifurcation curve of periodic orbits for continuous piecewise linear systems, numerical continuation is done to get some primary bifurcation curves for the piecewise linear Chua's oscillator in certain dimensionless parameter plane. The primary period doubling, homoclinic and saddle-node of periodic orbits' bifurcation curves are computed. A Belyakov point is detected in organizing the connection of these curves. In the parametric region between period-doubling, focus-center-limit cycle and homoclinic bifurcation curves, chaotic attractors coexist with stable nontrivial equilibria. The primary saddle-node bifurcation curve plays a leading role in this coexistence phenomenon.
PEANO'S THEOREM AND ATTRACTORS FOR LATTICE DYNAMICAL SYSTEMS
Authors: MORILLAS FRANCISCO , VALERO JOSÉ
Published: May 2009

In this paper, we prove the existence of solutions for first order lattice dynamical systems with continuous nonlinear term obtained via discretization of a reaction–diffusion system. Since the uniqueness of the Cauchy problem is not guaranteed, we define a multivalued semiflow and prove the existence of a global compact attractor.
CHAOTIC VIBRATIONS OF THE ONE-DIMENSIONAL MIXED WAVE SYSTEM
Authors: HU CHUNG-CHE
Published: May 2009

In this paper, we consider the initial-boundary value problem of the one-dimensional linear mixed wave equation ωtt - dωtx - c2ωxx = 0 (d ∈ ℝ, c > 0) on an interval, where the boundary condition at the left endpoint is linear, pumping energy into the system, while the boundary condition at the right endpoint has odd-degree nonlinearity. This problem is said to be the one-dimensional mixed wave system. The solution of the one-dimensional mixed wave system corresponds to the iteration of an interval map h. Thus, the mixed wave system is said to be chaotic if the interval map h is chaotic in the sense of Li–Yorke. In this paper, we show that the mixed wave system is chaotic under some conditions.
FORECASTING OF BIFURCATION PHENOMENA IN DYNAMICS OF PULSE ENERGY CONVERTERS WITH PARAMETER UNCERTAINTIES
Authors: KOLOKOLOV YURY V. , MONOVSKAYA ANNA V.
Published: May 2009

The results of bifurcation analysis seem to be used somehow or other as the basis of any method in nonlinear dynamics forecasting. The peculiarity of the problem setting in the paper is related to the fact that dynamics forecasting supposes the recognition of a bifurcation phenomenon before its beginning. In particular, this problem setting is important from the viewpoint of practical application of pulse energy converters (PEC). So, the necessity of real-time estimation of the direction of transient convergence appears. The complexity of such estimation is stipulated by the information on transients that is not mapped in bifurcation diagrams, and also time series do not contain preliminary information on a nonlinear dynamics picture. Moreover, PEC operation under parameter uncertainties leads to information on a bifurcation boundary location becomes fuzzy. The symbolic description of dynamical processes over time is offered with the purpose of the problem solution. This description is provided by the use of fractal regularities in the geometrical structures of phase trajectories, which are stipulated by the physical essence of both PWM process and transient convergence towards a limit cycle.
SOLUTIONS OF THE SCHRÖDINGER–POISSON PROBLEM CONCENTRATING ON SPHERES, PART II: EXISTENCE
Authors: IANNI ISABELLA
Published: May 2009

The Schrödinger–Poisson system describes standing waves for the nonlinear Schrödinger equation interacting with the electrostatic field.

We deal with the semiclassical states for this system and prove the existence of radial solutions concentrating on spheres in the presence of an external potential and with a non-constant density charge.

In particular, we show that the necessary conditions obtained in Part I are also sufficient if suitable non-degeneracy conditions are assumed.

We use a perturbation technique in a variational setting.
A 1D MODEL FOR A CLOSED RIGID FILAMENT IN STOKES FLOW
Authors: CAUSSIGNAC PH.
Published: May 2009

We adapt an existing asymptotic method to set up a one-dimensional model for the fall of a closed filament in an infinite fluid in the Stokes regime. Starting from the single-layer integral representation of the fluid velocity around the filament, we get, for a very slender filament, a Fredholm integral equation on the filament centerline. From this equation, we can compute the drag and force acting on the filament and consequently the resistance matrix. The integral equation is discretized with a collocation method. The study of a scalar model problem yields existence and uniqueness results together with an error estimate for the discretization scheme. Then, we compare the resistance matrix of thin ideal knots obtained from the discretization of the present model to a boundary element method; numerical convergence results and a good agreement of both methods validate our model.
A CLASS OF GAMES WITH COUPLED CONSTRAINTS TO MODEL INTERNATIONAL GHG EMISSION AGREEMENTS
Authors: BAHN O. , HAURIE A.
Published: May 2009

This paper deals with the design of equilibrium solutions with coupled constraints in dynamic games of greenhouse gas (GHG) emissions abatement. Self enforcing International Environmental Agreements (IEA) among different groups of countries call for Nash equilibrium solutions when the abatement strategies of the countries are defined. In this paper we study the effect of having another party, like e.g. the United Nations which would impose to all players a coupled constraint on the total emissions allowed over the 21st century, or on the concentration of carbon reached at the end of the century. We show, using different formulations of environmental game, that the normalized equilibria obtained under a coupled constraint on emissions or concentration is close to Pareto optimality. This gives a clue on the way the post Kyoto negotiations could yield an agreement which could be close to efficiency.
PARAMETER ANALYSIS OF A ZERO-SUM DIFFERENTIAL GAME APPROXIMATING A NONZERO-SUM GAME
Authors: MELIKYAN ARIK , OLSDER GEERT JAN , AKHMETZHANOV ANDREI
Published: May 2009

In this paper we consider a zero-sum differential game in feedback setting with one state coordinate and finite time horizon. The problem is characterized by two parameters. This game arises as an approximation to a nonzero-sum game. Using analytical and numerical methods we solve the HJBI equation and give the description of the optimal feedback controls for both players. These feedbacks are given in terms of switching curves and singular universal lines. We also determine the change (bifurcations) of the optimal phase portrait of the game depending upon the parameters. In conclusion, we show that for some values of the parameters the solution of the considered zero-sum game leads to the exact solution of the corresponding nonzero-sum game, and for the other values of the parameters it supplies just some approximation.
SOLVABILITY OF LINEAR-QUADRATIC DIFFERENTIAL GAMES ASSOCIATED WITH PURSUIT-EVASION PROBLEMS
Authors: SHINAR JOSEF , TURETSKY VLADIMIR , GLIZER VALERY Y. , IANOVSKY EDUARD
Published: May 2009

A finite horizon zero-sum linear-quadratic differential game with a generalized cost functional, involving a Lebesgue integral with a measure that has both discrete and distributed parts, is considered. Sufficient conditions for the solvability of such a game are established in terms of the eigenvalues of an integral operator in Hilbert space. The game solution is based on solving an impulsive Riccati matrix differential equation. These results are applied for two games associated with pursuit-evasion problems. Illustrative examples are presented.
THE AGENCIES METHOD FOR MODELING COALITIONS AND COOPERATION IN GAMES
Authors: NASH JOHN F.
Published: May 2009

The idea leading to this study originated some time ago when I talked at a gathering of high school graduates at a summer science camp. I spoke about the theme of "the evolution of cooperation" (in Nature) and about how that topic was amenable to studies involving Game Theory (which, more frequently, has been used in research in economics).

After that event I was stimulated to think of the possibility of modeling cooperation in games through actions of acceptance in which one player could simply accept the "agency" of another player or of an existing coalition of players.

The action of acceptance would have the form of being entirely cooperative, as if "altruistic", and not at all competitive, but there was also the idea that the game would be studied under circumstances of repetition and that every player would have the possibility of reacting in a non-cooperative fashion to any undesirable pattern of behavior of any another player. Thus the game studied would be analogous to the repeated games of "Prisoner's Dilemma" variety that have been studied in theoretical biology.

These studies of "PD" (or "Prisoner's Dilemma") games have revealed the paradoxical possibility of the natural evolution of cooperative behavior when the interacting organisms or species are presumed only to be endowed with self-interested motivations, thus motivations of a non-cooperative type.
Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations
Authors: Mee Lisa , Nabokina Svetlana M. , Sekar V. Thillai , Subramanian Veedamali S. , Maedler Kathrin , Said Hamid M.
Published: May 2009

Thiamin is essential for the normal function of the endocrine pancreas, but very little is known about uptake mechanism(s) and regulation by beta cells. We addressed these issues using mouse-derived pancreatic beta-TC-6 cells, and freshly isolated primary mouse and human pancreatic islets. Results showed that thiamin uptake by beta-TC-6 cells involves a pH (but not Na+)-dependent carrier-mediated process that is saturable at both the nanomolar (apparent Km= 37.17 ± 9.9 nM) and micromolar (apparent Km= 3.26 ± 0.86 μM) ranges, cis-inhibited by thiamin structural analogs, and trans-stimulated by unlabeled thiamin. Involvement of carrier-mediated process was also confirmed in primary mouse and human pancreatic islets. Both THTR-1 and THTR-2 were found to be expressed in these mouse and human pancreatic preparations. Maintaining beta-TC-6 cells in the presence of a high level of thiamin led to a significant ( P < 0.01) decrease in thiamin uptake, which was associated with a significant downregulation in level of expression of THTR-1 and THTR-2 at the protein and mRNA levels and a decrease in transcriptional (promoter) activity. Modulators of intracellular Ca2+/calmodulin- and protein-tyrosine kinase-mediated pathways also altered thiamin uptake. Finally, confocal imaging of live beta-TC-6 cells showed that clinical mutants of THTR-1 have mixed expression phenotypes and all led to impairment in thiamin uptake. These studies demonstrate for the first time that thiamin uptake by the endocrine pancreas is carrier mediated and is adaptively regulated by the prevailing vitamin level via transcriptional mechanisms. Furthermore, clinical mutants of THTR-1 impair thiamin uptake via different mechanisms.
Adrenomedullin reduces intestinal epithelial permeability in vivo and in vitro
Authors: Temmesfeld-Wollbrück Bettina , Brell Bernhard , zu Dohna Corinna , Dorenberg Martin , Hocke Andreas C. , Martens Holger , Klar Jürgen , Suttorp Norbert , Hippenstiel Stefan
Published: May 2009

Leakage of the gut mucosal barrier in the critically ill patient may allow translocation of bacteria and their virulence factors, thereby perpetuating sepsis and inflammation. Present evidence suggests that adrenomedullin (AM) improves endothelial barrier function and stabilizes circulatory function in systemic inflammation. We tested the hypothesis that exogenously applied AM stabilizes gut epithelial barrier function. Infusion of Staphylococcus aureus α-toxin induced septic shock in rats. AM infusion in a therapeutic setting reduced translocation of labeled dextran from the gut into the systemic circulation in this model. AM also reduced α-toxin and hydrogen peroxide (H2O2)-related barrier disruption in Caco-2 cells in vitro and reduced H2O2-related rat colon barrier malfunction in Ussing chamber experiments. AM was shown to protect endothelial barrier function via cAMP elevation, but AM failed to induce cAMP accumulation in Caco-2 cells. cAMP is degraded via phosphodiesterases (PDE), and Caco-2 cells showed high activity of cAMP-degrading PDE3 and 4. However, AM failed to induce cAMP accumulation in Caco-2 cells even in the presence of sufficient PDE3/4 inhibition, whereas adenylyl cyclase activator forskolin induced strong cAMP elevation. Furthermore, PDE3/4 inhibition neither amplified AM-induced epithelial barrier stabilization nor affected AM cAMP-related rat colon short-circuit current, furthermore indicating that AM may act independently of cAMP in Caco-2 cells. Finally, experiments using chemical inhibitors indicated that PKC, phosphatidylinositide 3-kinase, p38, and ERK did not contribute to AM-related stabilization of barrier function in Caco-2 cells. In summary, during severe inflammation, elevated AM levels may substantially contribute to the stabilization of gut barrier function.
Validation of a one-dimensional model of the systemic arterial tree
Authors: Reymond Philippe , Merenda Fabrice , Perren Fabienne , Rüfenacht Daniel , Stergiopulos Nikos
Published: May 2009

A distributed model of the human arterial tree including all main systemic arteries coupled to a heart model is developed. The one-dimensional (1-D) form of the momentum and continuity equations is solved numerically to obtain pressures and flows throughout the systemic arterial tree. Intimal shear is modeled using the Witzig-Womersley theory. A nonlinear viscoelastic constitutive law for the arterial wall is considered. The left ventricle is modeled using the varying elastance model. Distal vessels are terminated with three-element windkessels. Coronaries are modeled assuming a systolic flow impediment proportional to ventricular varying elastance. Arterial dimensions were taken from previous 1-D models and were extended to include a detailed description of cerebral vasculature. Elastic properties were taken from the literature. To validate model predictions, noninvasive measurements of pressure and flow were performed in young volunteers. Flow in large arteries was measured with MRI, cerebral flow with ultrasound Doppler, and pressure with tonometry. The resulting 1-D model is the most complete, because it encompasses all major segments of the arterial tree, accounts for ventricular-vascular interaction, and includes an improved description of shear stress and wall viscoelasticity. Model predictions at different arterial locations compared well with measured flow and pressure waves at the same anatomical points, reflecting the agreement in the general characteristics of the “generic 1-D model” and the “average subject” of our volunteer population. The study constitutes a first validation of the complete 1-D model using human pressure and flow data and supports the applicability of the 1-D model in the human circulation.
Region-specific adaptations in determinants of rat skeletal muscle oxygenation to chronic hypoxia
Authors: Wüst R. C. I. , Jaspers R. T. , van Heijst A. F. , Hopman M. T. E. , Hoofd L. J. C. , van der Laarse W. J. , Degens H.
Published: May 2009

Chronic exposure to hypoxia is associated with muscle atrophy (i.e., a reduction in muscle fiber cross-sectional area), reduced oxidative capacity, and capillary growth. It is controversial whether these changes are muscle and fiber type specific. We hypothesized that different regions of the same muscle would also respond differently to chronic hypoxia. To investigate this, we compared the deep (oxidative) and superficial (glycolytic) region of the plantaris muscle of eight male rats exposed to 4 wk of hypobaric hypoxia (410 mmHg, Po2: 11.5 kPa) with those of nine normoxic rats. Hematocrit was higher in chronic hypoxic than control rats (59% vs. 50%, P < 0.001). Using histochemistry, we observed 10% fiber atrophy ( P < 0.05) in both regions of the muscle but no shift in the fiber type composition and myoglobin concentration of the fibers. In hypoxic rats, succinate dehydrogenase (SDH) activity was elevated in fibers of each type in the superficial region (25%, P < 0.05) but not in the deep region, whereas in the deep region but not the superficial region the number of capillaries supplying a fiber was elevated (14%, P < 0.05). Model calculations showed that the region-specific alterations in fiber size, SDH activity, and capillary supply to a fiber prevented the occurrence of anoxic areas in the deep region but not in the superficial region. Inclusion of reported acclimatization-induced increases in mean capillary oxygen pressure attenuated the development of anoxic tissue areas in the superficial region of the muscle. We conclude that the determinants of tissue oxygenation show region-specific adaptations, resulting in a marked differential effect on tissue Po2.
IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice
Authors: Yu Qianli , Vazquez Randy , Khojeini Elham Vali , Patel Chirag , Venkataramani Raj , Larson Douglas F.
Published: May 2009

Osteopontin (OPN), a key component of the extracellular matrix, is associated with the fibrotic process during tissue remodeling. OPN and the cytokine interleukin (IL)-18 have been shown to be overexpressed in an array of human cardiac pathologies. In the present study, we determined the role of IL-18 in the regulation of cardiac OPN expression and the subsequent interstitial fibrosis and diastolic dysfunction. We demonstrated parallel increases in IL-18, OPN expression, and interstitial fibrosis in murine models of left ventricular pressure and volume overload. Exogenous recombinant (r)IL-18 administered for 2 wk increased cardiac OPN expression, interstitial fibrosis, and diastolic dysfunction. Stimulation of the T helper (Th)1 lymphocyte phenotype with a selective toll-like receptor (TLR)9 agonist induced cardiac IL-18 and OPN expression, which was associated with increased cardiac fibrillar collagen concentrations and interstitial fibrosis resulting in diastolic dysfunction. rIL-18 induced OPN expression and protein levels in primary of cardiac fibroblast cultures. Conditioned media from TLR9-stimulated T lymphocyte cultures induced IL-18 and OPN expression in cardiac fibroblasts, while blockade of the IL-18 receptor with a neutralizing antibody abolished the increase in OPN expression. Furthermore, a mutation in the transcriptional factor interferon regulatory factor (IRF)1 or IRF1 small interfering RNA (siRNA) resulted in the decreased expression of IL-18 and OPN in cardiac fibroblasts. With pressure overload, IRF1-mutant mice showed downregulation of IL-18 and OPN expression in cardiac tissue, reduced cardiac fibrotic development, and increased left ventricular function compared with wild type. These results provide direct evidence that the induction of IL-18 regulates OPN-mediated cardiac fibrosis and diastolic dysfunction.
Active middle-aged men have lower fasting inflammatory markers but the postprandial inflammatory response is minimal and unaffected by physical activity status
Authors: Dixon Natalie C. , Hurst Tina L. , Talbot Duncan C. S. , Tyrrell Rex M. , Thompson Dylan
Published: May 2009

Physical activity modifies some postprandial responses such as glycemic control, although it is unclear whether this translates into lower postprandial inflammation. Our objective in this study was to determine whether postprandial inflammatory markers are lower in active compared with sedentary middle-aged men. Thirteen active and twelve sedentary middle-aged men consumed a mixed meal on one occasion. Blood was taken via a cannula before and up to 8 h after the meal and with a single-use needle before and 8 h after the meal. Active men had lower fasted IL-6 (0.6 ± 0.2 vs. 1.2 ± 0.3 pg/ml; P = 0.004) and C-reactive protein (1.3 ± 0.3 vs. 2.9 ± 0.6 mg/l; P = 0.04) concentrations than sedentary men. Cannula blood IL-6 concentrations increased by 3.49 pg/ml in the 8 h following the meal ( P < 0.001); however, this increase was minimal (0.36 pg/ml) in blood taken via a single-use needle from the contralateral arm ( P = 0.013). The sedentary group had larger glucose ( P = 0.034), insulin ( P = 0.013), and triacylglycerol ( P = 0.057) responses to the meal. These results provide further evidence that physical activity is associated with lower inflammatory marker concentrations in a fasted state and a lower postprandial metabolic response to a meal. However, this does not translate into lower postprandial inflammatory markers since the only evidence of postprandial inflammation (a large increase in serum IL-6) was actually due to the cannula used for blood sampling.
Improved predictive models for plasma glucose estimation from multi-linear regression analysis of exhaled volatile organic compounds
Authors: Lee Jane , Ngo Jerry , Blake Don , Meinardi Simone , Pontello Andria M. , Newcomb Robert , Galassetti Pietro R.
Published: May 2009

Exhaled volatile organic compounds (VOCs) represent ideal biomarkers of endogenous metabolism and could be used to noninvasively measure circulating variables, including plasma glucose. We previously demonstrated that hyperglycemia in different metabolic settings (glucose ingestion in pediatric Type 1 diabetes) is paralleled by changes in exhaled ethanol, acetone, and methyl nitrate. In this study we integrated these gas changes along with three additional VOCs (2 forms of xylene and ethylbenzene) into multi-linear regression models to predict plasma glucose profiles in 10 healthy young adults, during the 2 h following an intravenous glucose bolus (matched samples of blood, exhaled and room air were collected at 12 separate time points). The four-gas model with highest predictive accuracy estimated plasma glucose in each subject with a mean R value of 0.91 (range 0.70–0.98); increasing the number of VOCs in the model only marginally improved predictions (average R with best 5-gas model = 0.93; with 6-gas model = 0.95). While practical development of this methodology into clinically usable devices will require optimization of predictive algorithms on large-scale populations, our data prove the feasibility and potential accuracy of breath-based glucose testing.
Induction and Isolation of Vascular Cells From Human Induced Pluripotent Stem Cells—Brief Report
Authors: Taura Daisuke , Sone Masakatsu , Homma Koichiro , Oyamada Naofumi , Takahashi Kazutoshi , Tamura Naohisa , Yamanaka Shinya , Nakao Kazuwa
Published: May 2009

Objective—

Induced pluripotent stem (iPS) cells are a novel stem cell population derived from human adult somatic cells through reprogramming using a defined set of transcription factors. Our aim was to determine the features of the directed differentiation of human iPS cells into vascular endothelial cells (ECs) and mural cells (MCs), and to compare that process with human embryonic stem (hES) cells.

Methods and Results—

We previously established a system for differentiating hES cells into vascular cells. We applied this system to human iPS cells and examined their directed differentiation. After differentiation, TRA1–60
−
Flk1
+
cells emerged and divided into VE-cadherin-positive and -negative populations. The former were also positive for CD34, CD31, and eNOS and were consistent with ECs. The latter differentiated into MCs, which expressed smooth muscle α-actin and calponin after further differentiation. The efficiency of the differentiation was comparable to that of human ES cells.

Conclusions—

We succeeded in inducing and isolating human vascular cells from iPS cells and indicate that the properties of human iPS cell differentiation into vascular cells are nearly identical to those of hES cells. This work will contribute to our understanding of human vascular differentiation/development and to the development of vascular regenerative medicine.
Sphingosine-1-Phosphate
Authors: Michaud Maude D. , Robitaille Geneviève A. , Gratton Jean-Philippe , Richard Darren E.
Published: May 2009

Objective—

Sphingosine-1-phosphate (S1P) is a potent bioactive phospholipid responsible for a variety of vascular cell responses. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator of genes essential for adaptation to low oxygen. S1P and HIF-1 are both important mediators of vascular cell responses such as migation, proliferation, and survival. Studies have shown that nonhypoxic stimuli can activate HIF-1 in oxygenated conditions. Here, we attempt to determine whether S1P can modulate the vascular activation of HIF-1.

Methods and Results—

We show that in vascular endothelial and smooth muscle cells, activation of the S1P type-2 receptor by S1P strongly increases HIF-1α protein levels, the active subunit of HIF-1. This is achieved through pVHL-independent stabilization of HIF-1α. We demonstrate that the HIF-1 nuclear complex, formed on S1P stimulation, is transcriptionally active and specifically binds to a hypoxia-responsive elements. Moreover, S1P activates the expression of genes known to be closely regulated by HIF-1.

Conclusion—

Our results identify S1P as a novel and potent nonhypoxic activator of HIF-1. We believe that understanding the role played by HIF-1 in S1P gene regulation will have a strong impact on different aspects of vascular biology.
Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy
Authors: Carrière Audrey , Ebrahimian Téni G. , Dehez Stéphanie , Augé Nathalie , Joffre Carine , André Mireille , Arnal Samuel , Duriez Micheline , Barreau Corinne , Arnaud Emmanuelle , Fernandez Yvette , Planat-Benard Valérie , Lévy Bernard , Pénicaud Luc , Silvestre Jean-Sébastien , Casteilla Louis
Published: May 2009

Objective—

Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties.

Methods and Results—

The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mitochondrial ROS generation in ADSCs. We showed that transient stimulation of mitochondrial ROS generation in ADSCs before their injection in ischemic hindlimb strongly improved revascularization and the number of ADSC-derived CD31-positive cells in ischemic area. Mitochondrial ROS generation increased the secretion of the proangiogenic and antiapoptotic factors, VEGF and HGF, but did not affect ADSC ability to differentiate into endothelial cells, in vitro. Moreover, mitochondrial ROS-induced ADSC preconditioning greatly protect ADSCs against oxidative stress-induced cell death.

Conclusion—

Our study demonstrates that in vitro preconditioning by moderate mitochondrial ROS generation strongly increases in vivo ADSC proangiogenic properties and emphasizes the crucial role of mitochondrial ROS in ADSC fate.