bluuebunny/crossref_metadata_2025 huggingface dataset:
NONLINEAR DYNAMICSOF EVOKED NEUROMAGNETIC RESPONSES SIGNIFIES POTENTIAL DEFENSIVE MECHANISMS AGAINST PHOTOSENSITIVITY
Authors: BHATTACHARYA JOYDEEP , WATANABE KATSUMI , SHIMOJO SHINSUKE
Published: September 2004

We investigated the dynamical characteristics of neuromagnetic responses by recording magnetoencephalographic (MEG) signals to equiluminant flickering stimulus of different color combinations from a group of control subjects, and from a patient with photosensitive epilepsy. By wavelet based time-frequency analysis, we showed that two distinct neuromagentic responses corresponding to stimulus frequency and its time delayed first harmonic were found in control subjects, whereas no harmonic response was obtained for the patient. We applied a battery of methods (sample entropy measuring signal complexity and index of smoothness measuring determinism) based on nonlinear dynamical system theory in conjunction with bootstrapping surrogate analysis. The results suggested that a significant nonlinear structure was evident in the MEG signals for control subjects, whereas nonlinearity was not detected for the patient. In addition, the couplings between distant cortical regions were found to be greater for control subjects. The important role of combinational chromatic sensitivity in sustained cortical excitation was also confirmed. These findings lead to the hypothesis that the healthy human brain is most likely equipped with significantly nonlinear neuronal processing reflecting an inherent mechanism defending against hyper-excitation to chromatic flickering stimulus, and such nonlinear mechanism is likely to be impaired for a patient with photosensitive epilepsy.
BIFURCATION ANALYSIS ON A SELF-EXCITED HYSTERETIC SYSTEM
Authors: WU ZHIQIANG , YU PEI , WANG KEQI
Published: September 2004

This paper investigates periodic bifurcation solutions of a mechanical system which involves a van der Pol type damping and a hysteretic damper representing restoring force. This system has recently been studied based on the singularity theory for bifurcations of smooth functions. However, the results do not actually take into account the property of nonsmoothness involved in the system. In particular, the transition varieties due to constraint boundaries were ignored, resulting in failure in finding some important bifurcation solutions. To reveal all possible bifurcation patterns for such systems, a new method is developed in this paper. With this method, a continuous, piecewise smooth bifurcation problem can be transformed into several subbifurcation problems with either single-sided or double-sided constraints. Further, the constrained bifurcation problems are converted to unconstrained problems and then singularity theory is employed to find transition varieties. Explicit formulas are applied to reconsider the mechanical system. Numerical simulations are carried out to verify analytical predictions. Moreover, symbolic notation for a sequence of bifurcations is introduced to easily show the characteristics of bifurcations, and also the comparison of different bifurcations. The method developed in this paper can be easily extended to study bifurcation problems with other types of nonsmoothness.
BIFURCATION ANALYSIS OF DIFFERENTIAL-DIFFERENCE-ALGEBRAIC EQUATIONS
Authors: DU DONGYUN , TANG YUN
Published: September 2004

The dynamics of differential-difference-algebraic equations is studied. The paper extends the study of the local bifurcations to transcritical and pitchfork bifurcation under certain nondegenerate conditions using Lyapunov–Schmidt reduction. Furthermore, an improved version of singularity induced bifurcation theorem is given in this paper.
QUENCHING LORENZIAN CHAOS
Authors: HIDE RAYMOND , McSHARRY PATRICK E. , FINLAY CHRISTOPHER C. , PESKETT GUY D.
Published: September 2004

How fluctuations can be eliminated or attenuated is a matter of general interest in the study of steadily-forced dissipative nonlinear dynamical systems. Here, we extend previous work on "nonlinear quenching" [Hide, 1997] by investigating the phenomenon in systems governed by the novel autonomous set of nonlinear ordinary differential equations (ODE's) [Formula: see text], ẏ=-xzq+bx-y and ż=xyq-cz (where (x, y, z) are time(t)-dependent dimensionless variables and [Formula: see text], etc.) in representative cases when q, the "quenching function", satisfies q=1-e+ey with 0≤e≤1. Control parameter space based on a,b and c can be divided into two "regions", an S-region where the persistent solutions that remain after initial transients have died away are steady, and an F-region where persistent solutions fluctuate indefinitely. The "Hopf boundary" between the two regions is located where b=bH(a, c; e) (say), with the much studied point (a, b, c)=(10, 28, 8/3), where the persistent "Lorenzian" chaos that arises in the case when e=0 was first found lying close to b=bH(a, c; 0). As e increases from zero the S-region expands in total "volume" at the expense of F-region, which disappears altogether when e=1 leaving persistent solutions that are steady throughout the entire parameter space.
DYNAMIC COMPLEXITIES IN RATIO-DEPENDENT PREDATOR–PREY ECOSYSTEM MODELS WITH BIRTH PULSE AND PESTICIDE PULSE
Authors: HUI JING , CHEN LAN-SUN
Published: September 2004

In many models of pest control, increases in pest population due to birth are assumed to be continuous, but in fact, pest population reproduces only during a single period; at the same time, pesticides are often applied during the period. So in this paper we propose a ratio-dependent predator–prey model with birth pulse and pesticide pulse. Using the discrete dynamical system determined by the stroboscopic map, we obtain an exact periodic solution of systems which have Ricker functions or Beverton–Holt functions, and obtain the threshold conditions for their stability. Above the threshold, there is a characteristic sequence of bifurcations, leading to chaotic dynamics, which implies that the dynamical behaviors of the ratio-dependent predator–prey model with birth pulse and pesticide pulse are very complex, including small-amplitude oscillations, large-amplitude cycles and chaos. This suggests that birth pulse and pesticide pulse, in effect, provide a natural period or cyclicity that allows for period-doubling bifurcation and period-halving bifurcation route to chaos.
THE MALKUS–ROBBINS DYNAMO WITH A NONLINEAR SERIES MOTOR
Authors: MOROZ IRENE M.
Published: September 2004

In a recent paper Moroz [2003] considered a simplified version of third class self-exciting Faraday-disk dynamo model, introduced by Hide [1997], in the limit in which leads to the Malkus–Robbins dynamo [Malkus, 1972; Robbins, 1977] as a special case. In that study a linear series motor was incorporated which led to an enriching range of possible behavior that the original Malkus–Robbins dynamo could support. In this paper, we replace the linear motor by a nonlinear motor and consider the consequences on the dynamics of the dynamo.
GLOBAL PATTERNS FROM LOCAL INTERACTIONS: A DYNAMICAL SYSTEMS APPROACH
Authors: WIEDERIEN RICHARD J. , UDWADIA FIRDAUS E.
Published: September 2004

In this paper the global patterns that result from local interactions between players on a two-dimensional lattice are studied. The assumptions on interaction between players are based on the Prisoner's Dilemma game that has been used extensively in game theory and in the study of biological systems. Each player is located on a square lattice, and is assumed to cooperate or defect, based on mimicking the neighbor with the highest cumulative score from the preceding round of play. The edges of the lattice are glued to form a torus. Computer simulations are conducted for different sized lattices, different payoff values, and different initial conditions. Though the paper is primarily concerned with player behavior without self-interaction, some results with self-interaction are also included. The influence of "ideal" cooperators on the evolution of the system dynamics is also studied. Three generic regimes of behavior are identified. Complex global patterns with complicated dynamics and sometimes unpredictable results occur. Steady-state solutions, simple and complex periodic solutions, and traveling waves are observed depending on the initial conditions and the payoff values.
FUZZY CHAOS SYNCHRONIZATION VIA SAMPLED DRIVING SIGNALS
Authors: BARAJAS-RAMÍREZ JUAN GONZALO , CHEN GUANRONG , SHIEH LEANG S.
Published: September 2004

In this paper, a methodology to design a system that robustly synchronizes a master chaotic system from a sampled driving signal is developed. The method is based on the fuzzy Takagi–Sugeno representation of chaotic systems, from which a continuous-time fuzzy observer is designed as the solution of an LMI minimization problem such that the error dynamics have H∞disturbance attenuation performance. Then, from the dual-system approach, the fuzzy observer is digitally redesigned such that the performance is maintained for the sampled master system. The effectiveness of the proposed synchronization methodology is finally illustrated via numerical simulations of the chaotic Chen's system.
INTERMITTENT CHAOTIC OPERATION IN SWITCHING POWER CONVERTERS
Authors: WONG S. C. , TSE C. K. , TAM K. C.
Published: September 2004

In the process of designing and constructing switching power converters, chaotic operations are often observed intermittently between long periods of regular operations. In practice, such intermittent chaotic operations can be eliminated by incorporating appropriate design measures to combat interference of spurious signals. In this paper, we explain the mechanism that causes "intermittent" chaos in a popular type of switching converters, namely, current-mode controlled switching converters. The circuit model used to study the phenomenon incorporates a coupling process through which a spurious signal is coupled to the current sensing and ramp compensation circuitry, resulting in a modulation of the compensation slope which causes the system to become unstable intermittently. We show that coupling of spurious signals into the compensation ramp can cause intermittent chaotic or subharmonic operations.
STABILITY OF STEADY-STATE SOLUTIONS IN MULTIDIMENSIONAL COUPLED MAP LATTICES
Authors: DUBCOVÁ MIROSLAVA , TURZÍK DANIEL , KLÍČ ALOIS
Published: September 2004

Coupled map lattices with multidimensional lattice are considered. A method for the determination of the stability of spatially homogeneous and spatially periodic steady-state solutions is derived. This method is based on the determination of the spectrum of the linearized operator by means of Gelfand transformation of some appropriate Banach algebra. The results are applied to several examples.
GLOBAL EXPONENTIAL ROBUST STABILITY OF DELAYED NEURAL NETWORKS
Authors: LI XIAOLIN , CAO JINDE
Published: September 2004

In this paper, several simple and new conditions are presented to ensure existence, uniqueness and global exponential robust stability of the equilibrium point of neural networks with delays by using contraction mapping principle, homeomorphism property and Lyapunov method. The conditions given in this paper are easy to verify and apply, and the obtained results improve and extend to those in the literature. In addition, two examples are given to show the effectiveness of the proposed results.
ON THE STUDY OF LIMIT CYCLES OF THE GENERALIZED RAYLEIGH–LIENARD OSCILLATOR
Authors: WU YUHAI , HAN MAOAN , CHEN XIANFENG
Published: September 2004

The Hopf bifurcation, saddle connection loop bifurcation and Poincaré bifurcation of the generalized Rayleigh–Liénard oscillator Ẍ+aX+2bX3+ε(c3+c2X2+c1X4+c4Ẋ2)Ẋ=0 are studied. It is proved that for the case a<0, b>0 the system has at most six limit cycles bifurcated from Hopf bifurcation or has at least seven limit cycles bifurcated from the double homoclinic loop. For the case a>0, b<0 the system has at most three limit cycles bifurcated from Hopf bifurcation or has three limit cycles bifurcated from the heteroclinic loop.
CALCULATION OF ANOMALIES IN GAUGE THEORIES USING A GEOMETRIC APPROACH
Authors: BRACKEN PAUL
Published: September 2004

Gauge theory and anomalies which arise under quantization of these theories are formulated using differential geometric methods. The Wess–Zumino conditions are developed and some other relevant geometric properties of anomalies are mentioned. An elementary derivation of the non-Abelian anomaly in 2n dimensions is presented using this formalism.
CHARGE DENSITY DISTRIBUTIONS AND RELATED FORM FACTORS IN NEUTRON-RICH LIGHT EXOTIC NUCLEI
Authors: ANTONOV A. N. , GAIDAROV M. K. , KADREV D. N. , HODGSON P. E. , DE GUERRA E. MOYA
Published: September 2004

Charge form factors corresponding to proton density distributions in exotic nuclei, such as 6,8 He , 11 Li , 17,19 B and 14 Be are calculated and compared. The results can be used as tests of various theoretical models for the exotic nuclei structure in possible future experiments using a colliding electron-exotic nucleus storage ring. The result of such a comparison would show the effect of the neutron halo or skin on the proton distributions in exotic nuclei.
MUON DYNAMICS STUDIES IN MUON CATALYZED FUSION WITH WOLFENSTEIN–GERSTEIN EFFECT IN A SOLID H/D MIXTURE
Authors: ESKANDARI M. R. , MAHDAVI M.
Published: September 2004

In the pdμ system, fusion occurs from four incoherent hyperfine states, with varying combinations of pd nuclear spins (3/2 or 1/2). The two possible fusion products, 5.5 MeV gammas and 5.3 MeV conversion muons, is dependent on which nuclear hyperfine state the molecule is in (S=1/2 or 3/2). At low temperatures, the hyperfine splitting in the μd atom alters the final state of nuclear spins in the pdμ molecule. As deuterium concentration increases, so does the spin-flip rate, thus reducing the initial population of the quartet (S=3/2) nuclear spin of the pdμ molecule and enhancing the doublet (S=1/2) state. Since the fusion rates depend on the nuclear states, the quartet state only fuses with γ-emission, so having more of the doublet state changes the ratio of gamma to conversion muon yields. The doublet rate is dominant, thus total fusion yield increases with deuterium concentration until the lack of protium atoms significantly reduces the rate of pdμ molecule formation and ddμ fusion dominates completely. The kinematics of pdμ system are studied by Monte-Carlo method using "Lsode" computer code. The Wolfenstein–Gerstein effect and no-quartet theorem in the solid H/D mixture are considered by solving the muon dynamical equations for various deuterium concentrations. It is shown that the "no-quartet theorem" is not valid at low temperature and deuterium concentration, and is valid only if one neglects the mixed-symmetry components.
TWO-LEVEL BURN-IN FOR RELIABILITY AND ECONOMY IN REPAIRABLE SERIES SYSTEMS HAVING INCOMPATIBILITY
Authors: KIM KYUNGMEE O. , KUO WAY
Published: September 2004

When a system is assembled from components, incompatibility often occurs as a result of the assembly process. The ability to quantify incompatibility is very important for making burn-in decisions because the goal of system burn-in is to minimize the incompatibility factor. In the past, incompatibility has been only partially represented in the system prediction models because it was assumed that assembly had no effect on the components. This paper presents a more accurate model for system prediction by allowing for the possibility that, in some cases, assembly adversely affects the components. After applying a superposition of delayed renewal processes and a nonhomogeneous Poisson process for modeling times between system failures, we derive and analyze the effects of component and system burn-in on the system cost and performance. Examples are included to demonstrate how to determine optimal component and system burn-in times simultaneously based on an equivalent problem formation and nonlinear programming.
EXACT BAYESIAN ESTIMATION OF SYSTEM RELIABILITY WITH POTENTIAL MISCLASSIFICATIONS IN SAMPLING
Authors: TURKKAN N. , PHAM-GIA T.
Published: September 2004

We provide the exact expression of the reliability of a system under a Bayesian approach, using beta distributions as both native and induced priors at the system level, and allowing uncertainties in sampling, expressed under the form of misclassifications, or noises, that can affect the final posterior distribution. Exact 100(1-α)% highest posterior density credible intervals, for system reliability, are computed, and comparisons are made with results from approximate methods proposed in the literature.
RELIABILITY ANALYSIS AND SETTING RELIABILITY REQUIREMENTS BASED ON THE COST OF FAILURE
Authors: TODINOV M. T.
Published: September 2004

A theoretical framework and models are proposed for reliability analysis and setting reliability requirements based on the cost of failure. It is demonstrated that a high availability target does not necessarily limit the risk of failure or minimize the total losses. The proposed models include:

(i) models for determining the value from the reliability investment,

(ii) optimization models for minimizing the total losses,

(iii) models for limiting the risk of failure below a maximum acceptable level,

(iv) a model for guaranteeing an availability target and

(v) a model for guaranteeing a minimum failure-free operating interval before each random failure in a finite time interval.

The models related to the value from the reliability investment can be used to determine the effect from reducing early-life failures on the financial revenue.

On the basis of a counterexample it is demonstrated that altering the hazard rates of the components may lead to decreasing the probability of failure of the system and a simultaneous increase of the risk of failure, which shows that the cost-of-failure reliability analysis requires new reliability tools, different from the conventional tools.

A new closed-form relationship has been derived related to reliability associated with an overstress failure mechanism. On its basis, a method for setting reliability requirements has been proposed, which limits the risk of impact failure within a maximum acceptable level. On the basis of counterexamples, it has also been demonstrated that for a load and strength not following a normal distribution, the standard reliability measures "reliability index" and "loading roughness" can be misleading. A new reliability integral has been proposed, based on integration performed only within the region of the upper tail of the load distribution and the lower tail of the strength distribution.
A NON-PARAMETRIC TRAINABLE OBJECT-DETECTION MODEL USING A CONCEPT OF RETINOTOPIC SAMPLING
Authors: NIITSUMA HIROTAKA
Published: September 2004

A retina has a space-variant sampling mechanism and an orientation-sensitive mechanism. The space-variant sampling mechanism of the retina is called Retinotopic Sampling (RS). With these mechanisms, the object-detection is formulated as finding an appropriate coordinate transformation from a coordinate system on the input image to the retina. The appropriate coordinate transformation is found using maximum likelihood method. By using the model based on RS, we formulate a kernel function as an analytical function of the information on the input image, the position and the size of the object in the input image. Then the object-detection is realised as a gradient decent method for a discriminant function trained by Support Vector Machine (SVM). This detection mechanism realises faster detection than exploring a visual scene in raster-like fashion. The discriminant function outperforms results of SVMs using a kernel function using intensities of all pixels (based on independently published results), in face detection experiments over test images in the MIT-CBCL face database.
TEXTURE SEGMENTATION USING SEMI-SUPERVISED SUPPORT VECTOR MACHINES
Authors: SANEI SAEID
Published: September 2004

Segmentation of natural textures has been investigated by developing a novel semi-supervised support vector machines (S3VM) algorithm with multiple constraints. Unlike conventional segmentation algorithms the proposed method does not classify the textures but classifies the uniform-texture regions and the regions of boundaries. Also the overall algorithm does not use any training set as used by all other learning algorithms such as conventional SVMs. During the process, the images are restored from high spatial frequency noise. Then various-order statistics of the textures within a sliding two-dimensional window are measured. K-mean algorithm is used to initialise the clustering procedure by labelling part of the class members and the classifier parameters. Therefore at this stage we have both the training and the working sets. A non-linear S3VM is then developed to exploit both sets to classify all the regions. The convex algorithm maximises a defined cost function by incorporating a number of constraints. The algorithm has been applied to combinations of a number of natural textures. It is demonstrated that the algorithm is robust, with negligible misclassification error. However, for complex textures there may be a minor misplacement of the edges.
RECOGNITION OF SMILING FACES USING NEURAL NETWORKS AND SPCA
Authors: NAKANO MIYOKO , YASUKATA FUMIKO , FUKUMI MINORU
Published: September 2004

Research on "man-machine interface" has increased in many fields of engineering and its application to facial expressions recognition is expected. The eigenface method by using the principal component analysis (PCA) is popular in this research field. However, it is not easy to compute eigenvectors with a large matrix if the cost of calculation when applying it for time-varying processing is taken into consideration.

In this paper, in order to achieve high-speed PCA, the simple principal component analysis (SPCA) is applied to compress the dimensionality of portions that constitute a face. A value of cos θ is calculated using an eigenvector by SPCA as well as a gray-scale image vector of each picture pattern. By using neural networks (NNs), the difference in the value of cos θ between the true and the false (plastic) smiles is clarified and the true smile is discriminated. Finally, in order to show the effectiveness of the proposed face classification method for true or false smiles, computer simulations are done with real images. Furthermore, an experiment using the self-organisation map (SOM) is also conducted as a comparison.
VQ-BASED GRAY WATERMARK EMBEDDING SCHEME WITH GENETIC INDEX ASSIGNMENT
Authors: WANG FENG-HSING , JAIN LAKHMI C. , PAN JENG-SHYANG
Published: September 2004

A digital watermarking scheme based on vector quantisation (VQ) for gray watermark is proposed. It begins with the procedure of encoding the gray watermark, and embeds the encoded indices into the cover image in VQ domain then. To improve the performance of the watermarking scheme, a genetic index assignment (GIA) procedure, which modifies the signal of the watermark to suit the signal of the cover image, is proposed. The proposed gray watermark embedding scheme is easy to implement, requires no original cover image to be presented during extraction, expands the size of the used watermark, and provides better watermarked results. Experimental results will show the novelty and effectiveness of it.
BLIND SEPARATION OF MIXED KURTOSIS SIGNED SIGNALS USING PARTIAL OBSERVATIONS AND LOW COMPLEXITY ACTIVATION FUNCTIONS
Authors: CHINNASARN KRISANA , LURSINSAP CHIDCHANOK , PALADE VASILE
Published: September 2004

Although several highly accurate blind source separation algorithms have already been proposed in the literature, these algorithms must store and process the whole data set which may be tremendous in some situations. This makes the blind source separation infeasible and not realisable on VLSI level, due to a large memory requirement and costly computation. This paper concerns the algorithms for solving the problem of tremendous data sets and high computational complexity, so that the algorithms could be run on-line and implementable on VLSI level with acceptable accuracy. Our approach is to partition the observed signals into several parts and to extract the partitioned observations with a simple activation function performing only the "shift-and-add" micro-operation. No division, multiplication and exponential operations are needed. Moreover, obtaining an optimal initial de-mixing weight matrix for speeding up the separating time will be also presented. The proposed algorithm is tested on some benchmarks available online. The experimental results show that our solution provides comparable efficiency with other approaches, but lower space and time complexity.
ROBUST DIGITAL WATERMARKING BASED ON PRINCIPAL COMPONENT ANALYSIS
Authors: HIEN THAI DUY , CHEN YEN-WEI , NAKAO ZENSHO
Published: September 2004

We propose a robust digital watermarking technique based on Principal Component Analysis (PCA) and evaluate the effectiveness of the method against some watermark attacks. In this proposed method, watermarks are embedded in the PCA domain and the method is closely related to DCT or DWT based frequency-domain watermarking. The orthogonal basis functions, however, are determined by data and they are adaptive to the data. The presented technique has been successfully evaluated and compared with DCT and DWT based watermarking methods. Experimental results show robust performance of the PCA based method against most prominent attacks.
REAL-TIME BLIND SOURCE SEPARATION OF ACOUSTIC SIGNALS WITH A RECURSIVE APPROACH
Authors: DING SHUXUE , HUANG JIE , WEI DAMING
Published: September 2004

We propose an approach for real-time blind source separation (BSS), in which the observations are linear convolutive mixtures of statistically independent acoustic sources. A recursive least square (RLS)-like strategy is devised for real-time BSS processing. A normal equation is further introduced as an expression between the separation matrix and the correlation matrix of observations. We recursively estimate the correlation matrix and explicitly, rather than stochastically, solve the normal equation to obtain the separation matrix. As an example of application, the approach has been applied to a BSS problem where the separation criterion is based on the second-order statistics and the non-stationarity of signals in the frequency domain. In this way, we realise a novel BSS algorithm, called exponentially weighted recursive BSS algorithm. The simulation and experimental results showed an improved separation and a superior convergence rate of the proposed algorithm over that of the gradient algorithm. Moreover, this algorithm can converge to a much lower cost value than that of the gradient algorithm.
Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs
Authors: Gagliardi Anthony D. , Kuo Evan Y. W. , Raulic Sanda , Wagner Graham F. , DiMattia Gabriel E.
Published: September 2004

Stanniocalcin (STC)-2 was discovered by its primary amino acid sequence identity to the hormone STC-1. The function of STC-2 has not been examined; thus we generated two lines of transgenic mice overexpressing human (h)STC-2 to gain insight into its potential functions through identification of overt phenotypes. Analysis of mouse Stc2 gene expression indicates that, unlike Stc1, it is not highly expressed during development but exhibits overlapping expression with Stc1 in adult mice, with heart and skeletal muscle exhibiting highest steady-state levels of Stc2 mRNA. Constitutive overexpression of hSTC-2 resulted in pre- and postnatal growth restriction as early as embryonic day 12.5, progressing such that mature hSTC-2-transgenic mice are ∼45% smaller than wild-type littermates. hSTC-2 overexpression is sometimes lethal; we observed 26–34% neonatal morbidity without obvious dysmorphology. hSTC-2-induced growth retardation is associated with developmental delay, most notably cranial suture formation. Organ allometry studies show that hSTC-2-induced dwarfism is associated with testicular organomegaly and a significant reduction in skeletal muscle mass likely contributing to the dwarf phenotype. hSTC-2-transgenic mice are also hyperphagic, but this does not result in obesity. Serum Ca2+and PO4were unchanged in hSTC-2-transgenic mice, although STC-1 can regulate intra- and extracellular Ca2+in mammals. Interestingly, severe growth retardation induced by hSTC-2 is not associated with a decrease in GH or IGF expression. Consequently, similar to STC-1, STC-2 can act as a potent growth inhibitor and reduce intramembranous and endochondral bone development and skeletal muscle growth, implying that these tissues are specific physiological targets of stanniocalcins.
Reducing plasma HIV RNA improves muscle amino acid metabolism
Authors: Yarasheski Kevin E. , Smith Samuel R. , Powderly William G.
Published: September 2004

We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577–E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (≥1 log) increased muscle protein synthesis rate and reduced Ra Gln and muscle proteasome activity in 10 men and 1 woman (22–57 yr, 60–108 kg, 17–33 kg muscle) with advanced HIV (CD4 = 0–311 cells/μl; HIV RNA = 10–375 × 103 copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/μl, P = 0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P = 0.003). Mixed muscle protein synthesis rate increased (0.062 ± 0.005 vs. 0.078 ± 0.006%/h, P = 0.01), Ra Gln decreased (387 ± 33 vs. 323 ± 15 μmol·kg fat-free mass−1·h−1, P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% ( P = 0.03). Muscle mass was only modestly increased (1 kg, P = not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, ∼3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.
Role of microtubules in estradiol-17β-d-glucuronide-induced alteration of canalicular Mrp2 localization and activity
Authors: Mottino Aldo D. , Crocenzi Fernando A. , Pozzi Enrique J. Sánchez , Veggi Luis M. , Roma Marcelo G. , Vore Mary
Published: September 2004

Estradiol-17β-d-glucuronide (E2-17G) induces a marked but reversible inhibition of bile flow in the rat together with endocytic retrieval of multidrug resistance-associated protein 2 (Mrp2) from the canalicular membrane to intracellular structures. We analyzed the effect of pretreatment (100 min) with the microtubule inhibitor colchicine or lumicholchicine, its inactive isomer (1 μmol/kg iv), on changes in bile flow and localization and function of Mrp2 induced by E2-17G (15 μmol/kg iv). Bile flow and biliary excretion of bilirubin, an endogenous Mrp2 substrate, were measured throughout, whereas Mrp2 localization was examined at 20 and 120 min after E2-17G by confocal immunofluorescence microscopy and Western analysis. Colchicine pretreatment alone did not affect bile flow or Mrp2 localization and activity over the short time scale examined (3–4 h). Administration of E2-17G to colchicine-pretreated rats induced a marked decrease (85%) in bile flow and biliary excretion of bilirubin as well as internalization of Mrp2 at 20 min. These alterations were of a similar magnitude as in rats pretreated with lumicolchicine followed by E2-17G. Bile flow and Mrp2 localization and activity were restored to control levels within 120 min of E2-17G in animals pretreated with lumicolchicine. In contrast, in colchicine-pretreated rats followed by E2-17G, bile flow and Mrp2 activity remained significantly inhibited by 60%, and confocal and Western studies revealed sustained internalization of Mrp2 120 min after E2-17G. We conclude that recovery from E2-17G cholestasis, associated with exocytic insertion of Mrp2 in the canalicular membrane, but not its initial E2-17G-induced endocytosis, is a microtubule-dependent process.
Effect of corticosteroids on nitric oxide production in inflammatory bowel disease: are leukocytes the site of action?
Authors: Linehan John D. , Kolios George , Valatas Vassilis , Robertson Duncan A. F. , Westwick John
Published: September 2004

Nitric oxide (NO) production is increased in the human colonic mucosa in intestinal inflammation. We examined the effect of corticosteroids and the role of mononuclear cells in this production. Colonic biopsies from patients with ulcerative colitis and normal controls were cultured with either budesonide or prednisolone in the presence of proinflammatory cytokines. Human mixed mononuclear cells (MMCs) were cocultured with HT-29 cells stimulated with IFN-γ and LPS in the presence or absence of corticosteroids. Nitrite production was measured in supernatants by a modification of the Griess reaction, and inducible NO synthase (iNOS) mRNA expression was studied in colonic tissue by RT-PCR. Both steroids significantly suppressed the nitrite production and iNOS mRNA expression in inflamed colonic biopsies from ulcerative colitis patients and in cytokine-stimulated normal colonic biopsies but not in cytokine-stimulated HT-29 cells. Nitrite production by HT-29 cells was significantly increased ( P < 0.01) in cocultures with MMCs stimulated with IFN-γ and LPS. The presence of either prednisolone or budesonide significantly ( P < 0.01) suppressed nitrite production from cocultures of HT-29 cells and MMCs but not from cultures of HT-29 cells stimulated with conditioned media from activated MMCs. Interestingly, stimulation of HT-29 with conditioned media from MMCs pretreated with steroids before stimulation with LPS and IFN-γ induced a significantly ( P < 0.01) lower nitrite production. These results suggest that the inhibitory effect of corticosteroids on the NO production in the intestinal inflammation might be via the inhibition of MMC-produced mediators responsible for NO production by colonic epithelial cells.
Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs
Authors: Li Wei , Tanaka Kuniyoshi , Ihaya Akio , Fujibayashi Yasuhisa , Takamatsu Shinji , Morioka Kouichi , Sasaki Masato , Uesaka Takahiko , Kimura Tetsuya , Yamada Narihisa , Tsuda Takeshi , Chiba Yukio
Published: September 2004

Platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP), has been reported to possess angiogenic activity and to inhibit apoptosis. This study was performed to determine whether PD-ECGF/TP can be used to ameliorate chronic myocardial ischemia. Myocardial ischemia was created in 40 mongrel dogs by placement of an ameroid constrictor on the proximal left anterior descending coronary artery (LAD). Plasmid vector encoding human PD-ECGF/TP cDNA (pCIhTP group; n = 12), empty vector pCI (pCI group; n = 12), or saline (Saline group; n = 12) was directly injected into the LAD territory 3 wk after ameroid constrictor implantation. Myocardial blood flow was detected using PET at baseline, 3 wk after ameroid constrictor implantation, and 2 wk after therapeutic treatment. At the end of the experiment, the hearts were isolated for biological and histological analysis. In the pCIhTP group, the transfected heart strongly expressed PD-ECGF/TP. The size of the infarct was smaller in the pCIhTP group than in the pCI or Saline group. The number of apoptotic myocardial cells was decreased in the pCIhTP group compared with the control groups based on triple immunohistochemical staining for von Willebrand factor, α-actin smooth muscle cells, and single-strand DNA. The level of proapoptotic protein Bax markedly decreased in the pCIhTP group compared with the other groups. Double immunohistochemical staining for von Willebrand factor and α-actin smooth muscle cells demonstrated that angiogenesis and arteriogenesis occurred, and paralleled the changes in myocardial blood flow and myocardial function in the pCIhTP group. We conclude that genetic approaches using PD-ECGF/TP to target the myocardium are effective for alleviating chronic myocardial ischemia.
A point-process model of human heartbeat intervals: new definitions of heart rate and heart rate variability
Authors: Barbieri Riccardo , Matten Eric C. , Alabi AbdulRasheed A. , Brown Emery N.
Published: September 2004

Heart rate is a vital sign, whereas heart rate variability is an important quantitative measure of cardiovascular regulation by the autonomic nervous system. Although the design of algorithms to compute heart rate and assess heart rate variability is an active area of research, none of the approaches considers the natural point-process structure of human heartbeats, and none gives instantaneous estimates of heart rate variability. We model the stochastic structure of heartbeat intervals as a history-dependent inverse Gaussian process and derive from it an explicit probability density that gives new definitions of heart rate and heart rate variability: instantaneous R-R interval and heart rate standard deviations. We estimate the time-varying parameters of the inverse Gaussian model by local maximum likelihood and assess model goodness-of-fit by Kolmogorov-Smirnov tests based on the time-rescaling theorem. We illustrate our new definitions in an analysis of human heartbeat intervals from 10 healthy subjects undergoing a tilt-table experiment. Although several studies have identified deterministic, nonlinear dynamical features in human heartbeat intervals, our analysis shows that a highly accurate description of these series at rest and in extreme physiological conditions may be given by an elementary, physiologically based, stochastic model.
Right atrial dimension-pressure relation during volume expansion is unaltered by pregnancy in the rat
Authors: Hines Tina , Abhyankar Sarang S. , Veeh Jessica M.
Published: September 2004

Blood volume expands significantly during pregnancy, but afferent signals from cardiac receptors are reduced. In addition, during exogenous volume expansion, right atrial pressure (RAP) increases more for equivalent volumes in pregnant animals, implying reduced atrial compliance. To examine possible gestational alterations in atrial dimension during volume expansion, we compared the effects of volume expansion on RAP and right atrial dimension (RAD) in pregnant vs. virgin rats. Anesthetized animals were ventilated and catheterized for measurement of arterial pressure and RAP and for drug infusion. Through a parasternal incision, ultrasonic crystals were glued to the medial and lateral surfaces of the right atrium for measurement of RAD. Plasma volume and hematocrit were determined before experimentation. RAP, RAD, and arterial pressure were recorded at baseline and during progressive volume expansion (6% dextran, 60% of initial blood volume). Baseline RAP was similar in the two groups: 2.82 ± 0.40 and 2.72 ± 0.47 mmHg in pregnant and virgin rats, respectively. Basal RAD was significantly larger in pregnant than in virgin rats: 4.36 ± 0.66 vs. 3.36 ± 0.48 mm. Despite increased basal RAD in pregnant rats, the slope of the RAD-RAP relation during volume expansion was similar in the two groups. Results indicate that resting RAD is increased in pregnant rats and that the change in dimension during volume loads is similar to that in virgin rats. Thus, during pregnancy, the right atrium appears to accommodate the increased blood volume, and reduced afferent signaling most likely is due to mechanisms other than mechanical alterations of the atrium by expanded volume.
Peroxisome proliferator-activated receptors and cardiovascular remodeling
Authors: Schiffrin Ernesto L.
Published: September 2004

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: α, β/δ, and γ. The better known are PPAR-α and PPAR-γ, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR-α is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR-γ is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR-α (fibrates) and PPAR-γ (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects, such as weight gain, as well as documented aggravation of advanced heart failure through fluid retention by glitazones, may, however, limit their therapeutic application in prevention of cardiovascular disease.
Chronic ventricular myocyte-specific overexpression of angiotensin II type 2 receptor results in intrinsic myocyte contractile dysfunction
Authors: Nakayama Masaharu , Yan Xinhua , Price Robert L. , Borg Thomas K. , Ito Kenta , Sanbe Atsushi , Robbins Jeffrey , Lorell Beverly H.
Published: September 2004

ANG II type 2 receptor (AT2) is upregulated in failing hearts, but its effect on myocyte contractile function is not known. We measured fractional cell shortening and intracellular Ca2+concentration transients in left ventricular myocytes derived from transgenic mice in which ventricle-specific expression of AT2was driven by the myosin light chain 2v promoter. Confocal microscopy studies confirmed upregulation of AT2in the ventricular myocytes and partial colocalization of AT2with AT1. Three components of contractile performance were studied. First, baseline measurements (0.5 Hz, 1.5 mmol/l extracellular Ca2+concentration, 25°C) and study of contractile reserve at faster pacing rates (1–5 Hz) revealed Ca2+-dependent contractile dysfunction in myocytes from AT2transgenic mice. Comparison of two transgenic lines suggested a dose-dependent relationship between magnitude of contractile dysfunction and level of AT2expression. Second, activity of the Na+/H+exchanger, a dominant transporter that regulates beat-to-beat intracellular pH, was impaired in the transgenic myocytes. Third, the inotropic response to β-adrenergic versus ANG II stimulation differed. Both lines showed impaired contractile response to β-adrenergic stimulation. ANG II elicited an increase in contractility and intracellular Ca2+in wild-type myocytes but caused a negative inotropic effect in myocytes from AT2transgenic mice. In contrast with β-adrenergic response, the depressed response to ANG II was related to level of AT2overexpression. The depressed response to ANG II was also present in myocytes from young transgenic mice before development of heart failure. Thus chronic overexpression of AT2has the potential to cause Ca2+- and pH-dependent contractile dysfunction in ventricular myocytes, as well as loss of the inotropic response to ANG II.
Dynamics of virtual electrode-induced scroll-wave reentry in a 3D bidomain model
Authors: Sambelashvili Aleksandre , Efimov Igor R.
Published: September 2004

Functional reentry in the heart can be caused by a wave front of excitation rotating around its edge. Previous simulations on the basis of monodomain cable equations predicted the existence of self-sustained, vortex-like wave fronts (scroll waves) rotating around a filament in three dimensions. In our simulations, we used the more accurate bidomain model with modified Beeler-Reuter ionic kinetics to study the dynamics of scroll-wave filaments in a 16 × 8 × 1.5-mm slab of ventricular tissue with straight fibers. Wave fronts were identified as the areas with inward current. Their edges represented the filaments. Both transmural and intramural reentries with I- and U-shaped filaments, respectively, were obtained by the S1-S2 point stimulation protocol through the virtual electrode-induced phase singularity mechanism. The filaments meandered along elongated trajectories and tended to attach to the tissue boundaries exposed to air (no current flow) rather than to the bath (zero extracellular potential). They completely detached from electroporated (zero transmembrane potential) boundaries. In our simulations, the presence of the bath led to generation of only U-shaped filaments, which survived for the 1.5-mm-thick slab but not for the slabs of 0.5- or 3-mm thicknesses. Thus boundary conditions may be another determinant of the type and dynamics of reentry.
AKH-producing neuroendocrine cell ablation decreases trehalose and induces behavioral changes inDrosophila
Authors: Isabel Guillaume , Martin Jean-René , Chidami Saad , Veenstra Jan A. , Rosay Philippe
Published: September 2004

Adipokinetic hormone (AKH) is a metabolic neuropeptide principally known for its mobilization of energy substrates, notably lipid and trehalose during energy-requiring activities, such as flight and locomotion. Drosophila melanogaster AKH cell localization in corpora cardiaca, as in other insect species, was confirmed by immunoreactivity and by a genetic approach using the UAS/GAL4 system. To assess AKH general physiological rules, we ablated AKH endocrine cells by specifically driving the expression of apoptosis transgenes in AKH cells. Trehalose levels were decreased in larvae and starved adults, when the stimulation by AKH of the production of trehalose from fat body glycogen is no longer possible. Moreover, we show that these adults without AKH cells become progressively hypoactive. Finally, under starvation conditions, those hypoactive AKH-knockout cell flies survived ∼50% longer than control wild-type flies, suggesting that the slower rate at which AKH-ablated flies mobilize their energy resources extends their survival.