bluuebunny/crossref_metadata_2025 huggingface dataset:
MULTI-LAYER SEGMENTATION OF COMPLEX DOCUMENT IMAGES
Authors: WU BING-FEI , CHEN YEN-LIN , CHIU CHUNG-CHENG
Published: December 2005

Text is commonly printed on a complex background. Segmenting text is an important part in document analysis. In the past some methods have been shown for the segmentation of texts with images. However, previous studies have not sufficiently addressed complex compound documents. This investigation presents an algorithm for the segmentation of text in various document images. The proposed segmentation algorithm applies a new multilayer segmentation method to separate the text from various compound document images, independent from the text and background overlapping or not. This method solves various problems associated with the complexity of background images. Experimental results obtained using various document images scanned from book covers, advertisements, brochures and magazines, reveal that the proposed algorithm can successfully segment Chinese and English text strings from various backgrounds, regardless of whether the texts are over a simple, slowly varying or rapidly varying background texture.
A NOVEL FUZZY C-MEANS ALGORITHM AND ITS APPLICATION
Authors: YUAN KEHONG , WU LIANWEN , CHENG QIANSHENG , BAO SHANGLIAN , CHEN CHAO , ZHANG HONGJIE
Published: December 2005

The accurate and effective algorithm for segmenting image is very useful in many fields, especially in medical images. In this paper we introduced a novel method that focuses on segmenting the brain MR Image that is important for neural diseases. Because of many noises embedded in the acquiring procedure, such as eddy currents, susceptibility artifacts, rigid body motion and intensity inhomogeneity, segmenting the brain MR image is a difficult work. In this algorithm, we overcame the inhomogeneity shortage, by modifying the objective function by compensating its immediate neighborhood effect using Gaussian smooth method for decreasing the influence of the inhomogeneity and increasing the segmenting accuracy. Using simulate image and clinical MRI data, experiments show that our proposed algorithm is effective.
COMBINING MULTIPLE CLASSIFIERS BASED ON A STATISTICAL METHOD FOR HANDWRITTEN CHINESE CHARACTER RECOGNITION
Authors: LIN LEI , WANG XIAOLONG , YEUNG DANIEL
Published: December 2005

Combining multiple classifiers is a new method that achieves a substantial gain in performance in many areas of pattern recognition. This paper demonstrates a novel method (based on statistics) of combining multiple classifiers to address the task of recognizing handwritten Chinese characters. Fusion strategies are discussed to provide a basis for the architecture of the combined classifiers. The weights of these fusion strategies are assigned via a genetic algorithm (GA). These fusion strategies are then tested using our online system for handwritten Chinese character recognition. In addition, different combinatory approaches are tested for comparison purposes. These include the conventional approach that is based on the Bayesian principle and the improved weighted combination, employing shared and distinct representations. Our experimental results demonstrate the effectiveness of these combinatory approaches.
SCALING DARK ENERGY IN A FIVE-DIMENSIONAL BOUNCING COSMOLOGICAL MODEL
Authors: XU LIXIN , LIU HONGYA
Published: December 2005

We consider a five-dimensional Ricci flat bouncing cosmological model in which the four-dimensional induced matter contains two components at late times — the cold dark matter (CDM) + baryons and dark energy. We find that the arbitrary function f(z) contained in the solution plays a similar role as the potential V(ϕ) in quintessence and phantom dark energy models. To resolve the coincidence problem, it is generally believed that there is a scaling stage in the evolution of the universe. We analyze the condition for this stage and show that a hyperbolic form of the function f(z) can work well in this property. We find that during the scaling stage (before z ≈ 2), the dark energy behaves like (but not identical to) a cold dark matter with an adiabatic sound speed [Formula: see text] and px ≈ 0. After z ≈ 2, the pressure of the dark energy becomes negative. The transition from deceleration to acceleration happens at zT ≈ 0.8 which, as well as other predictions of the 5D model, agrees with current observations.
VISCOUS FRW COSMOLOGY IN MODIFIED GRAVITY
Authors: BREVIK I. , GORBUNOVA O. , SHAIDO Y. A.
Published: December 2005

We discuss a modified form of gravity implying that the action contains a power α of the scalar curvature. Coupling with the cosmic fluid is assumed. As equation of state for the fluid, we take the simplest version where the pressure is proportional to the density. Based upon a natural ansatz for the time variation of the scale factor, we show that the equations of motion are satisfied for a general α. Also the condition of conservation of energy and momentum is satisfied. Moreover, we investigate the case where the fluid is allowed to possess a bulk viscosity, and find the noteworthy fact that consistency of the formalism requires the bulk viscosity to be proportional to the power (2α-1) of the scalar expansion. In Einstein's gravity, where α = 1, this means that the bulk viscosity is proportional to the scalar expansion. This mathematical result is of physical interest; as discussed recently by the authors, there exists in principle a viscosity-driven transition of the fluid from the quintessence region into the phantom region, implying a future Big Rip singularity.
ANTI-DE SITTER CURVATURE RADIUS CONSTRAINED BY QUASARS IN BRANE-WORLD SCENARIOS
Authors: COIMBRA-ARAÚJO CARLOS H. , DA ROCHA ROLDÃO , PEDRON ISABEL TAMARA
Published: December 2005

This paper is intended to investigate the luminosity due to the accretion of gas in supermassive black holes (SMBHs) in the center of quasars, using a brane-world scenario naturally endowed with extra dimensions, whereon theories formulated introduce corrections in the field equations at high energies. SMBHs possess the necessary highly energetic environment for the introduction of these corrections, which are shown to produce small deviations in all SMBH properties and, consequently, corrections in the accretion theory that supports quasars radiative processes. The radiative flux observed from quasars indicates these deviations, from which the magnitude of the AdS 5 bulk curvature radius, and consequently the extra dimension compactification radius is estimated.
EXACT SOLUTIONS OF SO(3) NONLINEAR SIGMA MODEL IN A CONIC SPACE BACKGROUND
Authors: BEZERRA V. B. , ROMERO C. , CHERVON SERGEY
Published: December 2005

We consider a nonlinear sigma model coupled to the metric of a conic space. We obtain restrictions for a nonlinear sigma model to be a source of the conic space. We then study a nonlinear sigma model in the conic space background. We find coordinate transformations which reduce the chiral fields equations in the conic space background to field equations in Minkowski space–time. This enables us to apply the same methods for obtaining exact solutions in Minkowski space–time to the case of a conic space–time. In the case the solutions depend on two spatial coordinates we employ Ivanov's geometrical ansatz. We give a general analysis and also present classes of solutions in which there is dependence on three and four coordinates. We discuss with special attention the intermediate, instanton and meron solutions and their analogous in the conic space. We find differences in the total actions and topological charges of these solutions and discuss the role of the deficit angle.
ADIABATIC PARTICLE PRODUCTION WITH DECAYING Λ AND ANISOTROPIC UNIVERSE
Authors: BHANJA SISIR , CHAKRABORTY SUBENOY , DEBNATH UJJAL
Published: December 2005

Here we study an anisotropic model of the universe with constant energy per particle. A decaying cosmological constant and particle production in an adiabatic process are considered as the sources for the entropy. The statefinder parameters {r, s} are defined and their behavior are analyzed graphically in some cases.
WHAT IS THE SUSY MASS SCALE?
Authors: OPHER REUVEN , PELINSON ANA
Published: December 2005

The energy, or mass scale M SUSY , of the supersymmetry (SUSY) phase transition is, as yet, unknown. If it is very high (i.e. ≫103 GeV ), terrestrial accelerators will not be able to measure it. We determine M SUSY here by combining theory with the cosmic microwave background (CMB) data. Starobinsky suggested an inflationary cosmological scenario in which inflation is driven by quantum corrections to the vacuum Einstein's equation. The modified Starobinsky model (MSM) is a natural extension of this. In the MSM, the quantum corrections are the quantum fluctuations of the supersymmetric (SUSY) particles, whose particle content creates inflation and whose masses terminate it. Since the MSM is difficult to solve until the end of the inflation period, we assume here that an effective inflaton potential (EIP) that reproduces the time dependence of the cosmological scale factor of the MSM can be used to make predictions for the MSM. We predict the SUSY mass scale to be M SUSY ≃ 1015 GeV , thus satisfying the requirement that the predicted density fluctuations of the MSM is in agreement with the observed CMB data.
IS THERE A RELATIONSHIP BETWEEN THE MASS OF A SMBH AND THE KINETIC ENERGY OF ITS HOST ELLIPTICAL GALAXY?
Authors: FEOLI A. , MELE D.
Published: December 2005

We use a restricted sample of elliptical galaxies, whose kinematical parameters inside the semi-major axis were calculated correcting for the effect of the integration of the light along the line of sight, in order to analyze a possible relationship between the mass of a supermassive black hole (SMBH) and the kinetic energy of random motions in the host galaxy. We find M BH ∝ (MG σ2)α with 0.87 ≤ α ≤ 1 depending on the different fitting methods and samples used. This result could be interpreted as a new fundamental relationship or as a new way to explain the old M BH - σ law. In fact, the relations of the velocity dispersion both with the mass of the SMBH (M BH ∝ σ4.12) and with the mass of the host galaxy (MG ∝ σ2.16) induce us to infer an almost direct proportionality: M BH ∝ MGσ2. A similar relationship is found for the total kinetic energy involving the rotation velocity too.
MODIFIED GR AND HELIUM NUCLEOSYNTHESIS
Authors: AL-RAWAF A. S.
Published: December 2005

We show that a previously proposed cosmological model based on the general relativity with non vanishing divergence for the energy–momentum tensor is consistent with the observed values for the nucleosynthesis of helium for some values of the arbitrary parameter α presented in this model. Furthermore values of α can be accommodated if we adopt the Randall–Sundrum single brane model.
LARGE-SCALE COSMOLOGICAL MAGNETIC FIELDS AND MAGNETIC HELICITY
Authors: SEMIKOZ V. B. , SOKOLOFF D. D.
Published: December 2005

Role of cosmological magnetic field and cosmological magnetic helicity for astrophysics is considered. We discuss possible mechanisms for cosmological magnetic field production in the early universe as well as upper observational estimate for such field. The general conclusion is that a substantial cosmological field with a non-vanishing magnetic helicity can be generated in the early universe and survive up to the epoch of galaxy formation.
Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells
Authors: Masamune Atsushi , Satoh Masahiro , Hirabayashi Jun , Kasai Kenichi , Satoh Kennichi , Shimosegawa Tooru
Published: December 2005

Galectin-1 is a β-galactoside-binding lectin. Previous studies have shown that galectin-1 was expressed in fibroblasts of chronic pancreatitis and of desmoplastic reaction associated with pancreatic cancer. These fibroblasts are now recognized as activated pancreatic stellate cells (PSCs). Here, we examined the role of galectin-1 in cell functions of PSCs. PSCs were isolated from rat pancreatic tissue and used in their culture-activated phenotype unless otherwise stated. Expression of galectin-1 was assessed by Western blot analysis, RT-PCR, and immunofluorescent staining. The effects of recombinant galectin-1 on chemokine production and proliferation were evaluated. Activation of transcription factors was assessed by EMSA. Activation of MAPKs was examined by Western blot analysis using anti-phosphospecific antibodies. Galectin-1 was strongly expressed in culture-activated but not freshly isolated PSCs. Recombinant galectin-1 increased proliferation and production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1. Galectin-1 activated ERK, JNK, activator protein-1, and NF-κB, but not p38 MAPK or Akt. Galectin-1 induced proliferation through ERK and chemokine production mainly through the activation of NF-κB and in part by JNK and ERK pathways. These effects of galectin-1 were abolished in the presence of thiodigalactosie, an inhibitor of β-galactoside binding. In conclusion, our results suggest a role of galectin-1 in chemokine production and proliferation through its β-galactoside binding activity in activated PSCs.
Nuclear compartmentalization of FAK and FRNK in cardiac myocytes
Authors: Yi Xian Ping , Zhou Jibin , Huber Lu , Qu Jiaxiang , Wang Xuejun , Gerdes A. Martin , Li Faqian
Published: December 2005

Focal adhesion kinase (FAK) and FAK-related non-kinase (FRNK) accumulate in the nucleus of cardiac myocytes during hypertensive hypertrophy. Nuclear FAK and FRNK are phosphorylated on different serines and form distinct bright spots. The subnuclear distribution of serine-phosphorylated FAK and FRNK was examined in this study by double labeling with fibrillarin, a component of nucleoli, and Sam68, a constituent of Sam68 nuclear bodies. We also investigated the role of protein kinase C (PKC)-mediated phosphorylation of FAK and FRNK on nuclear translocation. PKC activation by 12- O-tetradecanoylphorbol 13-acetate treatment increased serine phosphorylation of FAK and FRNK. Specifically, FAK was phosphorylated on serine 722 but not serine 910. On the other hand, FRNK was phosphorylated on serine 217, the equivalent site of FAK serine 910, but not serine 30, the homologous site of FAK serine 722. Serine-phosphorylated FAK and FRNK redistributed into the nucleus and formed distinct patterns. FAK with phosphorylation on serine 722 colocalized with Sam68 but not fibrillarin. On the contrary, FRNK phosphorylated on 217 coexisted with fibrillarin but not Sam68. Immunoprecipitation also confirmed that FAK associated with Sam68 and FRNK interacted with fibrillarin, respectively. These results suggest that FAK and FRNK target different nuclear subdomains by their association with distinct nuclear proteins.
Calpains: a physiological regulator of the endothelial barrier?
Authors: Gonscherowski Vera , Becker Bernhard F. , Moroder Louis , Motrescu Elena , Gil-Parrado Shirley , Gloe Torsten , Keller Matthias , Zahler Stefan
Published: December 2005

The intracellular protease calpain, abundant in endothelial cells (EC), is assumed to be inactive under physiological conditions but may account for Ca2+-linked pathophysiological events. However, nonstimulated EC contained autolyzed, activated calpain. Adding 12–48 μM calpain inhibitor I (CI) or 0.5–1 μM of the novel, membrane-permeable conjugate of calpastatin peptide-penetratin (CPP) caused rapid rounding and retraction of cultured EC (phase contrast, capacitance) and translocation of Syk, Rac, and Rho to the membrane, signifying activation upon inhibition of calpain. Isolated hearts (guinea pig) perfused with 12 μM CI or 0.5 μM CPP developed coronary leak. We conclude that calpain is constitutively active in EC and regulates vascular permeability by governing cell-cell attachment.
C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling
Authors: Khan Mahmood , Varadharaj Saradhadevi , Ganesan Latha P. , Shobha Jagdish C. , Naidu Madireddi U. , Parinandi Narasimham L. , Tridandapani Susheela , Kutala Vijay Kumar , Kuppusamy Periannan
Published: December 2005

We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes. Here we investigated the cardioprotective effect of PC against ischemia-reperfusion (I/R)-induced myocardial injury in an isolated perfused Langendorff heart model. Rat hearts were subjected to 30 min of global ischemia at 37°C followed by 45 min of reperfusion. Hearts were perfused with PC (10 μM) or Spirulina preparation (SP, 50 mg/l) for 15 min before the onset of ischemia and throughout reperfusion. After 45 min of reperfusion, untreated (control) hearts showed a significant decrease in recovery of coronary flow (44%), left ventricular developed pressure (21%), and rate-pressure product (24%), an increase in release of lactate dehydrogenase and creatine kinase in coronary effluent, significant myocardial infarction (44% of risk area), and TdT-mediated dUTP nick end label-positive apoptotic cells compared with the preischemic state. PC or SP significantly enhanced recovery of heart function and decreased infarct size, attenuated lactate dehydrogenase and creatine kinase release, and suppressed I/R-induced free radical generation. PC reversed I/R-induced activation of p38 MAPK, Bax, and caspase-3, suppression of Bcl-2, and increase in TdT-mediated dUTP nick end label-positive apoptotic cells. However, I/R also induced activation of ERK1/2, which was enhanced by PC treatment. Overall, these results for the first time showed that PC attenuated I/R-induced cardiac dysfunction through its antioxidant and antiapoptotic actions and modulation of p38 MAPK and ERK1/2.
Vascular adrenergic tone and structural narrowing constrain reactive hyperemia in skeletal muscle of obese Zucker rats
Authors: Frisbee Jefferson C.
Published: December 2005

Previous studies have demonstrated that skeletal muscle perfusion is impaired in obese Zucker rats (OZR) under control conditions and with elevated metabolic demand versus responses in lean Zucker rats (LZR). To further our understanding of processes contributing to impaired perfusion, we determined whether hyperemic responses following periods of occlusion were altered in skeletal muscle of OZR versus LZR. In isolated hindlimbs, basal blood flow in OZR was less than in LZR, and total perfusion responses after 30, 90, and 180 s of occlusion were reduced. Treatment of animals with an antioxidant (polythethylene glycol-superoxide dismutase) had no effect on reactive hyperemia, although blockade of α-adrenoreceptors (α1 > α2) improved responses to 30 and 90 s of occlusion; responses to 180 s of occlusion were unaltered. Pump perfusion of a dilated distal hindlimb demonstrated that increased volume flow elicited a greater increase in perfusion pressure in OZR versus LZR, suggesting structural contributions to an increased vascular resistance. Responses were comparable for in situ cremaster muscle because reactive hyperemia following serial arteriolar occlusion was attenuated in OZR versus LZR, treatment with polythethylene glycol-superoxide dismutase was ineffective, and hyperemic responses were improved following inhibition of α-adrenoreceptors (α1 > α2). Treatment of cremaster muscle with adenosine (10−3 M) caused flow to increase to a level comparable to that following 180 s of occlusion in both strains, although this level was reduced in OZR versus LZR. These results suggest that increased adrenergic tone may constrain reactive hyperemia in OZR with brief occlusion, although structural increases in vascular resistance can contribute to constrained perfusion after longer periods of occlusion.
Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth
Authors: Zhang Quiyang , Moe Orson W. , Garcia Joseph A. , Hsia Connie C. W.
Published: December 2005

We previously found increased expression of erythropoietin receptor (EPO-R) in peripheral dog lung during postnatal and postpneumonectomy (PNX) lung growth. To study the upstream regulation of EPO-R, we analyzed the expression of hypoxia-inducible factors (HIF)-1α, -2α, and -3α during postnatal lung growth in immature and mature (2.5 and 12 mo old, respectively) dogs and during compensatory lung growth 3 wk and 10 mo after right PNX. Relative to their respective controls, HIF-1α transcript was 52–95% higher in immature lungs and 284% higher in the remaining lung 3 wk post-PNX. HIF-2α transcript did not change during maturation but was 42% lower 3 wk post-PNX. HIF-3α transcript was 53–65% lower in both the immature lung and 3 wk post-PNX. Changes were no longer detectable 10 mo post-PNX. No change in HIF transcripts was observed in kidney and liver post-PNX. Consistent with the mRNA changes, HIF-1α protein was 120 and 196% higher in growing lungs and 3 wk post-PNX relative to their respective controls. Overexpression of HIF-1α in cultured HEK-293 cells increased endogenous expression of EPO-R protein. These results demonstrate regulated expression of the HIF system and parallel changes in HIF-1α and EPO-R expression during two types of lung growth. Because the normal growing lung is not hypoxic, the HIF system likely responds to other signals encountered during sustained lung strain.
The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia
Authors: Moriyama Maiko , Fukuyama Satoru , Inoue Hiromasa , Matsumoto Takafumi , Sato Takahiro , Tanaka Kentaro , Kinjyo Ichiko , Kano Tatsuhiko , Yoshimura Akihiko , Kojima Masayasu
Published: December 2005

Neuromedin U (NMU) is a neuropeptide expressed not only in the central nervous system but also in various organs, including the gastrointestinal tract and lungs. NMU interacts with two G protein-coupled receptors, NMU-R1 and NMU-R2. Although NMU-R2 is expressed in a specific region of the brain, NMU-R1 is expressed in various peripheral tissues, including immune and hematopoietic cells. Our recent study demonstrated an important role of NMU in mast cell-mediated inflammation. In this study, we showed that airway eosinophilia was reduced in NMU-deficient mice in an allergen-induced asthma model. There were no differences in the antigen-induced Th2 responses between wild-type and NMU knockout mice. NMU-R1 was highly expressed in the eosinophil cell line, and NMU directly induced Ca2+mobilization and extracellular/signal-regulated kinase phosphorylation. NMU also induced cell adhesion to components of the extracellular matrix (fibronectin and collagen type I), and chemotaxis in vitro. Furthermore, NMU-R1 was also expressed in human peripheral blood eosinophils, and NMU induced cell adhesion in a dose-dependent manner. These data indicate that NMU promotes eosinophil infiltration into inflammatory sites by directly activating eosinophils. Our study suggests that NMU receptor antagonists could be novel targets for pharmacological inhibition of allergic inflammatory diseases, including asthma.
Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury
Authors: Mendez Michael P. , Morris Susan B. , Wilcoxen Steven , Greeson Elizabeth , Moore Bethany , Paine Robert
Published: December 2005

Intercellular adhesion molecule-1 (ICAM-1; CD54) is an adhesion molecule constitutively expressed in abundance on the cell surface of type I alveolar epithelial cells (AEC) in the normal lung and is a critical participant in pulmonary innate immunity. At many sites, ICAM-1 is shed from the cell surface as a soluble molecule (sICAM-1). Limited information is available regarding the presence, source, or significance of sICAM-1 in the alveolar lining fluid of normal or injured lungs. We found sICAM-1 in the bronchoalveolar lavage (BAL) fluid of normal mice (386 ± 50 ng/ml). Additionally, sICAM-1 was spontaneously released by murine AEC in primary culture as type II cells spread and assumed characteristics of type I cells. Shedding of sICAM-1 increased significantly at later points in culture (5–7 days) compared with earlier time points (3–5 days). In contrast, treatment of AEC with inflammatory cytokines had limited effect on sICAM-1 shedding. BAL sICAM-1 was evaluated in in vivo models of acute lung injury. In hyperoxic lung injury, a reversible process with a major component of leak across the alveolar wall, BAL fluid sICAM-1 only increased in parallel with increased alveolar protein. However, in lung injury due to FITC, there were increased levels of sICAM-1 in BAL that were independent of changes in BAL total protein concentration. We speculate that after lung injury, changes in sICAM-1 in BAL fluid are associated with progressive injury and may be a reflection of type I cell differentiation during reepithelialization of the injured lung.
Increased pulmonary responses to acute ozone exposure in obese db/db mice
Authors: Lu Frank L. , Johnston Richard A. , Flynt Lesley , Theman Todd A. , Terry Raya D. , Schwartzman Igor N. , Lee Anna , Shore Stephanie A.
Published: December 2005

Epidemiological studies indicate the incidence of asthma is increased in obese and overweight humans. Responses to ozone (O3), an asthma trigger, are increased in obese ( ob/ob) mice lacking the satiety hormone leptin. The long form of leptin receptor (Ob-Rb) is required for satiety; mice lacking this receptor ( db/db mice) are also substantially obese. Here, wild-type (WT) and db/ db mice were exposed to air or O3 (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than WT mice after air exposure. O3-induced increases in pulmonary resistance and airway responsiveness were also greater in db/ db mice. BALF eotaxin, IL-6, KC, and MIP-2 increased 4 h after O3 exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O3 was significantly greater in db/ db than WT mice. Previously published results obtained in ob/ob mice were similar except for O3-induced neutrophils and MIP-2, which were not different from WT mice. O3 also induced pulmonary IL-1β and TNF-α mRNA expression in db/db but not ob/ob mice. Leptin was increased in serum of db/db mice, and pulmonary mRNA expression of short form of leptin receptor (Ob-Ra) was similar in db/db and WT mice. These data confirm obese mice have innate airway hyperresponsiveness and increased pulmonary responses to O3. Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-Rb but not Ob-Ra, suggest leptin, acting through Ob-Ra, can modify some pulmonary responses to O3.
Zn2+-induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway epithelial cells
Authors: Kim Yu-Mee , Reed William , Wu Weidong , Bromberg Philip A. , Graves Lee M. , Samet James M.
Published: December 2005

Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. IL-8 is an important proinflammatory cytokine in the human lung and is induced in human airway epithelial cells exposed to zinc. In this study, we examined the cellular mechanisms responsible for Zn2+-induced IL-8 expression. Zn2+ stimulation resulted in pronounced increases in both IL-8 mRNA and protein expression in the human airway epithelial cell line (BEAS-2B). IL-8 promoter activity was significantly increased by Zn2+ exposure in BEAS-2B cells, indicating that Zn2+-induced IL-8 expression is transcriptionally mediated. Mutation of the activating protein (AP)-1 response element in an IL-8 promoter-enhanced green fluorescent protein construct reduced Zn2+-induced IL-8 promoter activity. Moreover, Zn2+ exposure of BEAS-2B cells induced the phosphorylation of the AP-1 proteins c-Fos and c-Jun. We observed that Zn2+ exposure induced the phosphorylation of ERK, JNK, and p38 MAPKs, whereas inhibition of ERK or JNK activity blocked IL-8 mRNA and protein expression in BEAS-2B cells treated with Zn2+. In addition, we investigated the role of protein tyrosine phosphatases in the activation of signaling by Zn2+. Zn2+ treatment inhibited ERK- and JNK-directed phosphatase activities in BEAS-2B cells. These results suggested that Zn2+-induced inhibition of phosphatase activity is an initiating event in MAPK and AP-1 activation that leads to enhanced IL-8 expression by human airway epithelial cells.
Time-of-day-dependent effects of bright light exposure on human psychophysiology: comparison of daytime and nighttime exposure
Authors: Rüger Melanie , Gordijn Marijke C. M. , Beersma Domien G. M. , de Vries Bonnie , Daan Serge
Published: December 2005

Bright light can influence human psychophysiology instantaneously by inducing endocrine (suppression of melatonin, increasing cortisol levels), other physiological changes (enhancement of core body temperature), and psychological changes (reduction of sleepiness, increase of alertness). Its broad range of action is reflected in the wide field of applications, ranging from optimizing a work environment to treating depressed patients. For optimally applying bright light and understanding its mechanism, it is crucial to know whether its effects depend on the time of day. In this paper, we report the effects of bright light given at two different times of day on psychological and physiological parameters. Twenty-four subjects participated in two experiments ( n = 12 each). All subjects were nonsmoking, healthy young males (18–30 yr). In both experiments, subjects were exposed to either bright light (5,000 lux) or dim light <10 lux (control condition) either between 12:00 P.M. and 4:00 P.M. ( experiment A) or between midnight and 4:00 A.M. ( experiment B). Hourly measurements included salivary cortisol concentrations, electrocardiogram, sleepiness (Karolinska Sleepiness Scale), fatigue, and energy ratings (Visual Analog Scale). Core body temperature was measured continuously throughout the experiments. Bright light had a time-dependent effect on heart rate and core body temperature; i.e., bright light exposure at night, but not in daytime, increased heart rate and enhanced core body temperature. It had no significant effect at all on cortisol. The effect of bright light on the psychological variables was time independent, since nighttime and daytime bright light reduced sleepiness and fatigue significantly and similarly.
Tissue distribution of UT-A and UT-B mRNA and protein in rat
Authors: Doran John J. , Klein Janet D. , Kim Young Hee , Smith Tekla D. , Kozlowski Shelley D. , Gunn Robert B. , Sands Jeff M.
Published: December 2005

Mammalian urea transporters are facilitated membrane transport proteins belonging to two families, UT-A and UT-B. They are best known for their role of maintaining the renal inner medullary urinary concentrating gradient. Urea transporters have also been identified in tissues not typically associated with urea metabolism. The purpose of this study was to survey the major organs in rat to determine the distribution of UT-A and UT-B mRNA transcripts and protein forms and determine their cellular localization. Five kidney subregions and 17 extrarenal tissues were screened by Northern blot analysis using two UT-A and three UT-B probes and by Western blot analysis using polyclonal COOH-terminal UT-A and UT-B antibodies. Immunohistochemistry was performed on 16 extrarenal tissues using the same antibodies. In kidney, we detected mRNA transcripts and protein bands consistent with previously-identified UT-A and UT-B isoforms, as well as novel forms. We found that UT-A mRNA and protein are widely expressed in extrarenal tissues in various forms that are different from the known isoforms. We determined the cellular localization of UT-A and UT-B in these tissues. We found that both UT-A and UT-B are ubiquitously expressed as numerous tissue-specific mRNA transcripts and protein forms that are localized to cell membranes, cytoplasm, or nuclei.
Social defeat increases food intake, body mass, and adiposity in Syrian hamsters
Authors: Foster Michelle T. , Solomon Matia B. , Huhman Kim L. , Bartness Timothy J.
Published: December 2005

Overeating and increases in body and fat mass are the most common responses to day-to-day stress in humans, whereas stressed laboratory rats and mice respond oppositely. Group housing of Syrian hamsters increases body mass, adiposity, and food intake, perhaps due to social confrontation-induced stress. In experiment 1 we asked, Does repeated social defeat increase food intake, body mass, and white adipose tissue (WAT) mass in Syrian hamsters? Male hamsters subjected to the resident-intruder social interaction model and defeated intermittently 15 times over 34 days for 7-min sessions significantly increased their food intake, body mass, and most WAT masses compared with nondefeated controls. Defeat significantly increased terminal adrenal norepinephrine, but not epinephrine, content. In experiment 2 we asked, Are 15 intermittent resident-intruder interactions necessary to increase body mass and food intake? Body mass and food intake of subordinate hamsters defeated only once were similar to those of nondefeated controls, but four or eight defeats similarly and significantly increased these responses. In experiment 3 we asked, Do intermittent defeats increase adiposity and food intake more than consecutive defeats? Four intermittent or consecutive defeats similarly and significantly increased food intake and body mass compared with nondefeated controls, but only intermittent defeats significantly increased all WAT masses. Consecutive defeats significantly increased mesenteric and inguinal WAT masses. Plasma leptin, but not insulin, concentrations were similarly and significantly increased compared with nondefeated controls. Collectively, social defeat, a natural stressor, significantly increased food intake, body mass, and adiposity in Syrian hamsters and may prove useful in determining mechanisms underlying human stress-induced obesity.
Anatomical and functional characterization of clock gene expression in neuroendocrine dopaminergic neurons
Authors: Sellix Michael T. , Egli Marcel , Poletini Maristela O. , McKee De'Nise T. , Bosworth Matthew D. , Fitch Cheryl A. , Freeman Marc E.
Published: December 2005

Oscillations of gene expression and physiological activity in suprachiasmatic nucleus (SCN) neurons result from autoregulatory feedback loops of circadian clock gene transcription factors. In the present experiment, we have determined the pattern of PERIOD1 (PER1), PERIOD2 (PER2), and CLOCK expression within neuroendocrine dopaminergic (DAergic) neurons (NDNs) of ovariectomized (OVX) rats. We have also determined the effects of per1, per2, and clock mRNA knockdown in the SCN with antisense deoxyoligonucleotides (AS-ODN) on DA release from NDNs. Diurnal rhythms of PER1 and PER2 expression in tuberoinfundibular DAergic (TIDA) and periventricular hypophyseal DAergic (PHDA) neurons, peaked at circadian time (CT)18 and CT12, respectively. Rhythms of PER1 expression in tuberhypophyseal neuroendocrine DAergic (THDA) neurons were undetectable. Rhythms of PER2 expression were found in all three populations of NDNs, with greater levels of PER2 expression between CT6 and CT12. AS-ODN injections differentially affected DA turnover in the axon terminals of the median eminence (ME), neural lobe (NL) and intermediate lobe (IL) of the pituitary gland, resulting in a significant decrease in DA release in the early subjective night in the ME (TIDA), a significant increase in DA release at the beginning of the day in the IL (PHDA), and no effect in the NL (THDA). AS-ODN-treatment induced a rhythm of DA concentration in the anterior lobe, with greater DA levels in the middle of the day. These data suggest that clock gene expression, particularly PER1 and PER2, within NDNs may act to modulate diurnal rhythms of DA release from NDNs in the OVX rat.
Penile erection requires association of soluble guanylyl cyclase with endothelial caveolin-1 in rat corpus cavernosum
Authors: Linder A. Elizabeth , Leite Romulo , Lauria Kimberly , Mills Thomas M. , Webb R. Clinton
Published: December 2005

Erectile dysfunction is caused by a variety of pathogenic factors, particularly impaired formation and action of nitric oxide (NO). NO released from nerve endings and corpus cavernosum endothelial cells plays a crucial role in initiating and maintaining increased intracavernous pressure, penile vasodilatation, and penile erection. Classically, these effects are dependent on cGMP synthesized during activation of soluble guanylyl cyclase (sGC) by NO in smooth muscle cells. The enzyme NO synthase in endothelial cells has been localized to caveolae, small invaginations of the plasma membrane rich in cholesterol. Membrane cholesterol depletion impairs acetylcholine-induced relaxation in arteries attributed to an alteration in caveolar structure. It has been shown that sGC may be activated in endothelial caveolae contributing to vasodilation. We hypothesized that caveolae are the platform for sGC/cGMP signaling in cavernosum smooth muscle eliciting erection. Methyl-β-cyclodextrin, a pharmacological tool to deplete membrane cholesterol and disassemble caveolae, impaired rat erectile responses in vivo and cavernosum smooth muscle relaxation induced by the NO donor sodium nitroprusside and the sGC activator 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole in vitro. Methyl-β-cyclodextrin had no effect on cavernosum smooth muscle relaxation induced by NO released upon nerve stimulation or by exogenous cGMP. Furthermore, sGC and caveolin-1, the major coat protein of caveolae, were colocalized in rat corpus cavernosum sinusoidal endothelium. Electron microscopy indicated caveolae disruption in corpus cavernosum treated with methyl-β-cyclodextrin. In summary, our results provide evidence of compartmentalization of sGC in the caveolae of cavernosal endothelial cells contributing to NO signaling mediating smooth muscle relaxation and erection.
Purinergic receptors in human placenta: evidence for functionally active P2X4, P2X7, P2Y2, and P2Y6
Authors: Roberts V. H. J. , Greenwood S. L. , Elliott A. C. , Sibley C. P. , Waters L. H.
Published: December 2005

Appropriate regulation of ion transport by the human placental syncytiotrophoblast is important for fetal growth throughout pregnancy. In nonplacental tissues, ion transport can be modulated by extracellular nucleotides that raise intracellular calcium ([Ca2+]i) via activation of purinergic receptors. We tested the hypothesis that purinergic receptors are expressed by human placental cytotrophoblast cells and that their activation by extracellular nucleotides modulates ion (K+) efflux and [Ca2+]i. P2X/P2Y receptor agonists 5-bromouridine 5′-triphosphate (5-BrUTP), ADP, ATP, 2′,3′- O-(4-benzoyl-benzoyl)adenosine 5′-triphosphate (BzATP), and UTP stimulated86Rb (K+tracer) efflux from cultured cytotrophoblast cells at early (mononuclear) or later (multinucleate syncytiotrophoblast-like) stages of differentiation, with ATP and UTP particularly potent. 2-Methylthioadenosine 5′-triphosphate (2-MeS-ATP), and UDP elevated86Rb efflux only from multinucleated cells. All agonists caused a significant peak and plateau increase in [Ca2+]i, although the magnitude of responses was variable. The effect of BzATP, UTP, and UDP in multinucleated cells was unaffected, and that of ATP partially inhibited, by removal of extracellular Ca2+, implicating P2Y receptor activation. mRNA encoding P2X1,P2X2, P2X4, and P2X7and P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11were identified in mono- and multinucleated cells, whereas P2X3and P2X5mRNA were absent from all samples. Western blot analysis revealed P2X4, P2X7, P2Y2, and P2Y6protein in cytotrophoblast cells, but P2Y4was not detected. On the basis of published agonist selectivity, the data indicate the presence of functionally active P2X4, P2X7, P2Y2, and P2Y6receptors in cytotrophoblast cells. We propose that activation of these receptors, and subsequent elevation of [Ca2+]i, modulates syncytiotrophoblast homeostasis and/or maternofetal ion exchange in response to extracellular nucleotides.
Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure
Authors: Uemura Kazunori , Kamiya Atsunori , Hidaka Ichiro , Kawada Toru , Shimizu Shuji , Shishido Toshiaki , Yoshizawa Makoto , Sugimachi Masaru , Sunagawa Kenji
Published: December 2005

Pharmacological support with inotropes and vasodilators to control decompensated hemodynamics requires strict monitoring of patient condition and frequent adjustments of drug infusion rates, which is difficult and time-consuming, especially in hemodynamically unstable patients. To overcome this difficulty, we have developed a novel automated drug delivery system for simultaneous control of systemic arterial pressure (AP), cardiac output (CO), and left atrial pressure (Pla). Previous systems attempted to directly control AP and CO by estimating their responses to drug infusions. This approach is inapplicable because of the difficulties to estimate simultaneous AP, CO, and Pla responses to the infusion of multiple drugs. The circulatory equilibrium framework developed previously (Uemura K, Sugimachi M, Kawada T, Kamiya A, Jin Y, Kashihara K, and Sunagawa K. Am J Physiol Heart Circ Physiol 286: H2376–H2385, 2004) indicates that AP, CO, and Pla are determined by an equilibrium of the pumping ability of the left heart (SL), stressed blood volume (V), and systemic arterial resistance (R). Our system directly controls SLwith dobutamine, V with dextran/furosemide, and R with nitroprusside, thereby controlling the three variables. We evaluated the efficacy of our system in 12 anesthetized dogs with acute decompensated heart failure. Once activated, the system restored SL, V, and R within 30 min, resulting in the restoration of normal AP, CO, and Pla. Steady-state deviations from target values were small for AP [4.4 mmHg (SD 2.6)], CO [5.4 ml·min−1·kg−1(SD 2.4)] and Pla [0.8 mmHg (SD 0.6)]. In conclusion, by directly controlling the mechanical determinants of circulation, our system has enabled simultaneous control of AP, CO, and Pla with good accuracy and stability.
Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy
Authors: Haddad Fadia , Adams Gregory R.
Published: December 2005

Sarcopenia is an age-related loss of muscle mass and strength. The aged can increase various measures of muscle size and strength in response to resistance exercise (RE), but this may not normalize specific tension. In rats, aging reduces the hypertrophy response and impairs regeneration. In this study, we measured cellular and molecular markers, indicative of muscle hypertrophy, that also respond to acute increases in loading. Comparing 6- and 30-mo-old rats, the aims were to 1) determine whether these markers are altered with age and 2) identify age-sensitive responses to acute RE. The muscles of old rats exhibited sarcopenia involving a deficit in contractile proteins and decreased force generation. The RNA-to-protein ratio was higher in the old muscles, suggesting a decrease in translational efficiency. There was evidence of reduced signaling via components downstream from the insulin/insulin-like growth factor (IGF)-I receptors in old muscles. The mRNA levels of myostatin and suppressor of cytokine signaling 2, negative regulators of muscle mass, were lower in old muscles but did not decrease following RE. RE induced increases in the mRNAs for IGF-I, mechano-growth factor, cyclin D1, and suppressor of cytokine signaling 3 were similar in old and young muscles. RE induced phosphorylation of the IGF-I receptor, and Akt increased in young but not old muscles, whereas that of S6K1 was similar for both. The results of this study indicate that a number of components of intracellular signaling pathways are sensitive to age. As a result, key anticatabolic responses appear to be refractory to the stimuli provided by RE.
Effect of eccentric exercise on position sense at the human forearm in different postures
Authors: Walsh L. D. , Allen T. J. , Gandevia S. C. , Proske U.
Published: December 2005

This is a study of the ability of blindfolded human subjects to match the position of their forearms before and after eccentric exercise. The hypothesis tested was that the sense of effort contributed to forearm position sense. The fall in force after the exercise was predicted to alter the relationship between effort and force and thereby induce position errors. In the arms-in-front posture, subjects had their unsupported reference arm set to one of two angles from the horizontal, 30 or 60°, and they matched its position by voluntary placement of their other arm. Matching errors were compared with a task where the arms were counterweighted, so could be moved in the vertical plane with minimal effort, and where the arms were moved in the horizontal plane. In these latter two tasks, the intention was to test whether removal of an effort sensation from holding the arm against gravity influenced matching performance. It was found that, although absolute errors for counterweighted and horizontal matching were no larger than for unsupported matching, their standard deviations, 6.1 and 6.8°, respectively, were significantly greater than for unsupported matching (4.6°), indicating more erratic matching. The eccentric exercise led, the next day, to a fall in maximum voluntary muscle torque of ≥15%. This was accompanied by a significant increase in matching errors for the unsupported matching task from 2.7 ± 0.5 to 0.8 ± 0.7° but not for counterweighted (1.4 ± 0.2 to −0.2°± 1.1°) or horizontal matching (−1.3 ± 0.7° to −1.8 ± 0.7°). This, it is postulated, is because the reduced voluntary torque after exercise was accompanied by a greater effort required to support the arms, leading to larger matching errors. However, effort is only able to provide positional information for unsupported matching where gravity plays a role. In gravity-neutral tasks like counterweighted or horizontal matching, a change in the effort-force relationship after exercise leaves matching accuracy unaffected.
Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat
Authors: O’Leary Valerie B. , Marchetti Christine M. , Krishnan Raj K. , Stetzer Bradley P. , Gonzalez Frank , Kirwan John P.
Published: December 2005

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 ± 1 yr, body mass index = 33.2 ± 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 ± 0.8 vs. 24.3 ± 1.0 ml·kg−1·min−1, P < 0.0001), decreased body weight ( P < 0.0001) and fat mass ( P < 0.001), while fat-free mass was not altered ( P > 0.05). VF (176 ± 20 vs. 136 ± 17 cm2, P < 0.0001), subcutaneous fat (351 ± 34 vs. 305 ± 28 cm2, P < 0.03), and total abdominal fat (525 ± 40 vs. 443 ± 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower ( P < 0.003) after training, but total adiponectin and tumor necrosis factor-α remained unchanged. Insulin resistance was reversed by exercise (40.1 ± 7.7 vs. 27.6 ± 5.6 units, P < 0.01) and correlated with changes in VF ( r = 0.66, P < 0.01) and maximal oxygen consumption ( r = −0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.