bluuebunny/crossref_metadata_2025 huggingface dataset:
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: KREINOVICH VLADIK
Published: February 2004

This section is maintained by Vladik Kreinovich. Please send you abstract (or copies of papers that you want to see reviewed here) to vladik@cs.utep.edu, or by regular mail to: Vladik Kreinovich, Department of Computer Science, University of Texas at El Paso, El Paso, TX 79968, USA.
Si ADSORPTION ONSiC(0001) SURFACES
Authors: FISSEL ANDREAS , DĄBROWSKI JAREK
Published: February 2004

Activation energies and atomic geometries associated with Si adsorption and desorption processes on the Si face of SiC (0001) have been obtained from in situ reflection high-energy electron diffraction measurements and ab initio pseudopotential calculations. During the initial stage of Si deposition, the SiC (0001) surface develops a series of superstructures, depending on temperature and Si coverage. A kinetic diagram of the structural transformations during Si exposure or annealing is outlined and the adsorption energy Eais determined. The latter is found to be strongly affected by the surface structure and coverage, changing from 4.5 eV to 1.6 eV as the geometry of the Si adlayer changes from [Formula: see text] to (3×3). These observations are interpreted with the help of ab initio pseudopotential calculations. It is concluded that [Formula: see text] measured on [Formula: see text] corresponds to adsorption at adatom vacancy while Ea3=1.6 eV measured on (3×3) corresponds to adsorption on top of a capping adatom. Finally, the development of surface structures from the [Formula: see text] surface to silicon-rich and carbon-rich extremes is discussed.
STRUCTURE DETERMINATION OF THE 1 × 1GaN(0001) SURFACE BY QUANTITATIVE LOW ENERGY ELECTRON DIFFRACTION
Authors: YU Z. X. , TONG S. Y. , XU SHIHONG , MA SIMON , WU HUASHENG
Published: February 2004

A quantitative structural determination of the Ga-polar 1×1 (0001) surface of GaN is performed by quantitative low energy electron diffraction (LEED). The global best-fit structure is obtained by a new frozen LEED approach connected to a simulated annealing algorithm. The global minimization frozen (GMF) LEED search finds that the ordered structure consists of 1 ML of Ga adatoms at atop sites above Ga-terminated bilayers. The Ga adatoms are bonded with a Ga–Ga bond length of 2.51 Å. The spacings within surface bilayers show a weak oscillatory trend, with the outmost bilayer thickness expanding to 0.72 Å and the next bilayer thickness contracting to 0.64 Å, compared to the bulk thickness of 0.65 Å. The interlayer spacing between the first and second bilayers is 1.89 Å, while the next interlayer spacing is 1.94 Å, compared to the bulk value of 1.95 Å. These results are compared with data from other theoretical and experimental studies.
NUMERICAL STUDY OF THE FIRST ORDER IRREVERSIBLE PHASE TRANSITION IN THE ZIFF–GULARI–BARSHAD MODEL
Authors: ALBANO EZEQUIEL V. , MONETTI ROBERTO
Published: February 2004

The Ziff–Gulari–Barshad model [ZGB; Phys. Rev. Lett.56, 2553 (1986)] is a lattice gas adsorption–reaction model that qualitatively reproduces some relevant features of the oxidation of carbon monoxide on single crystal surfaces. We study the first order irreversible critical behavior of this model by means of two different types of simulation techniques, namely constant coverage simulations and epidemic analysis. Constant coverage simulations allow us to investigate in detail hysteretic and finite size effects within the coexistence region. The position of the coexistence point is accurately determined by introducing a small perturbation into the constant coverage method. Extensive epidemic simulations reveal the absence of power law behavior in the dynamic behavior at coexistence, in contrast to previous claims.
COMPLEX BEHAVIORS AT SIMPLE SEMICONDUCTOR AND METAL/SEMICONDUCTOR SURFACES
Authors: DÁVILA MARÍA E. , AVILA JOSÉ , ASENSIO MARÍA CARMEN , LAY GUY LE
Published: February 2004

We present in this article a comprehensive review of the dynamical fluctuations in the atomic positions that may take place, even at very low temperatures, at the clean silicon or germanium (100) surfaces or at their (111) surfaces decorated with Sn or Ag adatoms. We also elucidate the intriguing, hitherto unexplained differences observed between the two, seemingly similar, Sn/Si(111) and Sn/Ge(111) [Formula: see text] surfaces. We also describe the surprising behaviors of silver ultrathin films grown on different semiconductor surfaces, displaying in certain cases a bcc phase, a one-dimensional quasicrystalline superstructure and/or well-defined quantum size effects.
MEASUREMENT OF CRITICAL EXPONENTS OF NANOSTRUCTURED GOLD THIN FILMS
Authors: MELO L. L. , SALVADORI M. C. , CATTANI M.
Published: February 2004

We have fabricated gold thin films by metal plasma ion deposition on silicon substrates. The roughness of these nanostructured films has been measured by scanning tunneling microscopy (STM) and we have determined the growth dynamics critical exponents. We have also measured the grain sizes as a function of the film thickness.
PHOTOEMISSION STUDY OF THE REACTION OF CO WITH Sm FILMS ON THE Ru(001) SURFACE
Authors: RAO G. RANGA , NOZOYE H.
Published: February 2004

Photoemission spectroscopy (Ru 3d/C 1s and O 1s regions) has been used to investigate the formation of carbonate species on the Sm- and SmO x-covered Ru(001) surfaces at small exposures of CO. The results indicate that the reaction of ~ 1 L CO with disordered Sm layers on the Ru surface at 105 K produces surface carbonate and weakly bound CO 2 via the Boudouard reaction (2 COg → CO2,ad + Cad ). The latter species desorbs below 250 K, whereas the former is stable up to 500 K. The surface carbonate species is detected by the O 1s features as well as the C 1s feature developed in the Ru 3d region upon CO exposure. The CO reaction with the SmO x layer also leads to the formation of surface carbonate. The generation of carbonate on Sm and SmO x films seems to be related to the ionization of Sm atoms and the defects present in the partly oxidized Sm, respectively.
PROBING THE LOCAL DENSITY OF STATES OF DILUTE ELECTRON SYSTEMS IN DIFFERENT DIMENSIONS
Authors: MORGENSTERN MARKUS
Published: February 2004

Scanning tunneling spectroscopy at T = 6 K is used to investigate the local density of states (LDOS) of electron systems belonging to the bulk conduction band of InAs. In particular, the three-dimensional electron system (3DES) of the n-doped material, an adsorbate-induced two-dimensional electron system (2DES) and the tip-induced quantum dot (0DES) are investigated at B = 0 T and B = 6 T. It is found that the 3DES at B = 0 T can be described by Bloch states weakly interacting with the potential disorder provided by ionized dopants. The 2DES at B = 0 T exhibits much stronger LDOS corrugations, stressing the tendency for weak localization in the potential disorder. In a magnetic field, 3DES and 2DES show drift states, which are expected in 2D, but are surprising in 3D, where they point to a new electron phase consisting of droplets of quasi-2D systems.

The 0DES at B = 0 T reveals quantized states in accordance with Hartree calculations. At B = 6 T it exhibits Landau states with exchange enhanced spin splitting. These states are used to investigate the influence of potential disorder on the exchange enhancement, which visualizes the nonlocality of the exchange interaction.
CONVERSION OF THICKNESS DATA OF THIN FILMS WITH VARIABLE LATTICE PARAMETER FROM MONOLAYERS TO ANGSTROMS: AN APPLICATION OF THE EPITAXIAL BAIN PATH
Authors: BRAUN ARTUR
Published: February 2004

A procedure for the conversion of film thicknesses from monolayers to angstroms is presented. It is applicable to thickness data experimentally obtained from strained epitaxial films and based on the concept of the epitaxial Bain path. In particular, the in-plane lattice spacing of the film, such as that obtained with LEED on wedge-shaped samples, is used to determine the perpendicular lattice spacing, which serves for the conversion into angstroms. Omission of the implications of the Bain path concept would yield erroneous results. This conversion was successfully applied to compare experimental data, (given in monolayers), with data found in the literature (given in angstroms).
LEED INVESTIGATION OF THE Pb AND Sb ULTRATHIN LAYERS DEPOSITED ON THE Ni(111) FACE AT T=150–900 K
Authors: KRUPSKI A. , MRÓZ S.
Published: February 2004

The atomic structure of ultrathin lead and antimony layers deposited on the Ni (111) face in ultrahigh vacuum at a substrate temperature ranging from 150 to 900 K was investigated with the use of low-energy electron diffraction (LEED). LEED patterns corresponding to p(1×1), p(3×3), p(4×4), [Formula: see text] structures and p(1×1), p(2×2), [Formula: see text], [Formula: see text] structures for the adsorption of Pb and Sb, respectively, on the Ni (111) face were observed. Experimental LEED intensity-versus-energy [I(V)] spectra have been collected for the clean Ni (111) and for the [Formula: see text], [Formula: see text], [Formula: see text] structures. The I(V) curves obtained for the clean Ni (111) structure are in good agreement with experimental spectra from the literature.
AFM ANALYSIS OF QUANTUM DOT STRUCTURES INDUCED BY ION SPUTTERING WITH DIFFERENT TIPS
Authors: XU M. , TEICHERT C.
Published: February 2004

With tips of different hardness, we analyzed the effect of the hardness and shape of the actual AFM tip on the measurement of the best GaSb quantum dot (QD) structures induced by low energy Ar + sputtering. The comparison indicated that the complete information on the detailed dot shape and order structure can be determined with the hard and good tip, while with the soft or worn tip some information on the dot height and shape cannot be obtained. Our results suggest that, in order to obtain the complete surface information, the high hardness and good AFM tip should be used for semiconductor QD structures.
Statistical analyses of repeated measures in physiological research: a tutorial
Authors: Kristensen Michael , Hansen Thomas
Published: February 2004

Experimental designs involving repeated measurements on experimental units are widely used in physiological research. Often, relatively many consecutive observations on each experimental unit are involved and the data may be quite nonlinear. Yet evidently, one of the most commonly used statistical methods for dealing with such data sets in physiological research is the repeated-measurements ANOVA model. The problem herewith is that it is not well suited for data sets with many consecutive measurements; it does not deal with nonlinear features of the data, and the interpretability of the model may be low. The use of inappropriate statistical models increases the likelihood of drawing wrong conclusions. The aim of this article is to illustrate, for a reasonably typical repeated-measurements data set, how fundamental assumptions of the repeated-measurements ANOVA model are inappropriate and how researchers may benefit from adopting different modeling approaches using a variety of different kinds of models. We emphasize intuitive ideas rather than mathematical rigor. We illustrate how such models represent alternatives that 1) can have much higher interpretability, 2) are more likely to meet underlying assumptions, 3) provide better fitted models, and 4) are readily implemented in widely distributed software products.
Identification of multiple proteins whose synthetic rates are enhanced by high amino acid levels in rat hepatocytes
Authors: Jaleel Abdul , Nair K. Sreekumaran
Published: February 2004

Amino acids are key regulators of protein synthesis in liver. However, it remains to be determined whether amino acids stimulate synthesis of all or certain specific liver proteins. No techniques are currently available to simultaneously measure synthetic rates of several individual proteins. Here we report studies performed on rat hepatocyte primary cultures in which we used metabolic labeling with [14C]leucine, two-dimensional gel electrophoresis (2DGE), and tandem mass spectrometry to identify proteins that showed increased leucine incorporation when high amino acid levels were present in the media. Rat hepatocytes were isolated by in situ collagenase perfusion, cultured in serum-free medium containing insulin, and incubated for 2, 4, and 8 h in media of standard and high amino acid concentrations. SDS-PAGE and 2DGE were performed to separate proteins from cell lysates. Proteins that consistently showed increased synthesis on triplicate cultures, as detected by phosphorimaging of gels, were identified by tandom mass spectrometry. The combination of these approaches enabled the detection of 16 specific liver proteins whose synthetic rates were enhanced by increased amino acid concentration. These proteins are involved in specific functions such as translation intiation, protein folding and modification, oxidative phosphorylation, antioxidant defense, signal transduction, and transport, as well as cell motility and tissue integrity. No quantitative changes for any of these proteins were detected by gel staining, indicating that no detectable changes in protein concentration occurred. In contrast, measurable changes in synthetic rates occurred in 16 proteins. In conclusion, amino acids stimulate the synthesis of several liver proteins with important cellular functions.
Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion
Authors: Leclerc Isabelle , Woltersdorf Wolfram W. , da Silva Xavier Gabriela , Rowe Rebecca L. , Cross Sarah E. , Korbutt Greg S. , Rajotte Ray V. , Smith Richard , Rutter Guy A.
Published: February 2004

Metformin, a drug widely used in the treatment of type 2 diabetes, has recently been shown to act on skeletal muscle and liver in part through the activation of AMP-activated protein kinase (AMPK). Whether metformin or the satiety factor leptin, which also stimulates AMPK in muscle, regulates this enzyme in pancreatic islets is unknown. We have recently shown that forced increases in AMPK activity inhibit insulin secretion from MIN6 cells (da Silva Xavier G, Leclerc I, Varadi A, Tsuboi T, Moule SK, and Rutter GA. Biochem J 371: 761–774, 2003). Here, we explore whether 1) glucose, metformin, or leptin regulates AMPK activity in isolated islets from rodent and human and 2) whether changes in AMPK activity modulate insulin secretion from human islets. Increases in glucose concentration from 0 to 3 and from 3 to 17 mM inhibited AMPK activity in primary islets from mouse, rat, and human, confirming previous findings in insulinoma cells. Incubation with metformin (0.2–1 mM) activated AMPK in both human islets and MIN6 β-cells in parallel with an inhibition of insulin secretion, whereas leptin (10–100 nM) was without effect in MIN6 cells. These studies demonstrate that AMPK activity is subject to regulation by both glucose and metformin in pancreatic islets and clonal β-cells. The inhibitory effects of metformin on insulin secretion may therefore need to be considered with respect to the use of this drug for the treatment of type 2 diabetes.
Altered gene expression and increased bursting activity of colonic smooth muscle ATP-sensitive K+ channels in experimental colitis
Authors: Jin Xiaochun , Malykhina Anna P. , Lupu Florea , Akbarali Hamid I.
Published: February 2004

The ATP-sensitive K+ channel (KATP) is a complex composed of an inwardly rectifying, pore-forming subunit (Kir 6.1 and Kir 6.2) and the sulfonylurea receptor (SUR1 and SUR2). In gastrointestinal smooth muscle, these channels are important in regulating cell excitability. We examined the molecular composition of the KATP channel in mouse colonic smooth muscle and determined its activity in the pathophysiological setting of experimental colitis. Following 7 days of dextran sulfate sodium (DSS) treatment in drinking water, colonic inflammation was scored by histology and physical signs. In whole cell recordings, levcromakalim-induced currents were significantly larger in inflamed cells. In cell-attached patch recordings of single-channel events, levcromakalim enhanced the bursting duration in inflamed cells. The single-channel conductance of ∼42 pS was not altered with inflammation. mRNA for both Kir 6.1 and 6.2 were detected by RT-PCR. Kir 6.1 was localized to the plasma membrane, whereas Kir 6.2 was mainly detected in the cytosol by immunohistochemistry. Quantitative PCR showed that Kir 6.1 gene expression was upregulated by almost 22-fold, whereas SUR2B was downregulated by threefold after inflammation. Thus decreased motility of the colon during inflammation may be associated with changes in the transcriptional regulation of Kir 6.1 and SUR2B gene expression.
Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat model of enteritis
Authors: Porras Monica , Martín María Teresa , Soler Mercè , Vergara Patri
Published: February 2004

The aims of this study were: 1) to obtain an experimental model reproducing the characteristics of chronicity and spontaneous relapses found in inflammatory bowel disease (IBD) and 2) to correlate these changes with intestinal motility and bacteria translocation. For this purpose, two groups of Sprague-Dawley rats were used: a treated group that received two subcutaneous injections of indomethacin (7.5 mg/kg) 48 h apart and a control group that received saline. Blood leukocytes, TNF, and fecal parameters were monitored for 90 days after treatment. In treated rats, a cyclic oscillation of blood leukocytes and TNF concomitant with an inverse correlation of fecal output was observed. Treated rats were then selected either during their highest or lowest blood leukocyte values for motor activity and microbiological evaluation. Controls were obtained in age-matched rats. Rats with high leukocyte levels showed a decrease of motor activity. In contrast, animals with low leukocyte levels presented hypermotility. Bacterial overgrowth accompanied by bacterial translocation was found in the group with high leukocytes, whereas no differences were observed between the control and indomethacin groups during the lowest leukocyte phase. We obtained a model of IBD characterized by a chronic cyclic oscillation of intestinal motility, flora, and inflammatory blood parameters. During the high-leukocyte stage, motor activity decrease is related to bacterial translocation. This phase is followed by a reactive one characterized by hypermotility associated with a decrease in both bacterial growth and leukocytes. However, as in IBD, this reaction seems unable to prevent a return to relapse.
Gene transfer of a novel vasoactive natriuretic peptide stimulates cGMP and lowers blood pressure in mice
Authors: Pan Shuchong , Gulati Rajiv , Mueske Cheryl S. , Witt Tyra A. , Lerman Amir , Burnett John C. , Simari Robert D.
Published: February 2004

Dendroaspis natriuretic peptide (DNP) is a recently described peptide produced by Dendroaspis angusticeps with structural and functional similarities to mammalian natriuretic peptides. These similarities suggest a potential role for DNP in cardiovascular therapeutics. To determine the physiological effects of chronic delivery of DNP, a gene transfer approach using first generation adenoviral vectors was utilized. Although the gene for DNP has not been cloned in any species, the peptide sequence in the snake is known. Preferred mammalian codons for snake DNP were cloned downstream of either the leader sequence (referred to as pBDNP-1) or prepropeptide sequence of human brain natriuretic peptide (BNP) cDNA (referred to as pBDNP-2). Transfections with pBDNP-1 or pBDNP-2 resulted in expected forms of chimeric DNP (cDNP) in cell lysates and conditioned media. Functional studies demonstrated the ability of both forms of cDNP within conditioned media to stimulate cGMP production in human vascular smooth muscle cells (hVSMC). Expressed cDNP inhibited hVSMC proliferation and stimulated vasorelaxation in a similar fashion. To investigate the chronic physiological effects of administration of cDNP, an adenoviral vector expressing cDNP (Ad-BDNP) was generated. Intravenous delivery of Ad-BDNP in mice resulted in dose-dependent systemic expression of cDNP. The highest level of expression was associated with consistent elevation of its presumed second messenger (cGMP) for 21 days but with transient lowering of systolic blood pressure in normotensive mice. This study demonstrates the biological features of the expression of the xenogenic peptide DNP.
P2Y purine receptor responses and expression in the pulmonary circulation of juvenile rabbits
Authors: Konduri Girija G. , Bakhutashvili Ivane , Frenn Recia , Chandrasekhar Indira , Jacobs Elizabeth R. , Khanna Ashwani K.
Published: February 2004

The purine nucleotide ATP mediates pulmonary vasodilation at birth by stimulation of P2Y purine receptors in the pulmonary circulation. The specific P2Y receptors in the pulmonary circulation and the segmental distribution of their responses remain unknown. We investigated the effects of purine nucleotides, ATP, ADP, and AMP, and pyrimidine nucleotides, UTP, UDP, and UMP, in juvenile rabbit pulmonary arteries for functional characterization of P2Y receptors. We also studied the expression of P2Y receptor subtypes in pulmonary arteries and the role of nitric oxide (NO), prostaglandins, and cytochrome P-450 metabolites in the response to ATP. In conduit size arteries, ATP, ADP, and AMP caused greater relaxation responses than UTP, UDP, and UMP. In resistance vessels, ATP and UTP caused comparable vasodilation. The response to ATP was attenuated by the P2Y antagonist cibacron blue, the NO synthase antagonist Nω-nitro-l-arginine methyl ester (l-NAME), and the cytochrome P-450 inhibitor 17-octadecynoic acid but not by the P2X antagonist α,β-methylene ATP or the cyclooxygenase inhibitor indomethacin in conduit arteries. In the resistance vessels, l-NAME caused a more complete inhibition of the responses to ATP and UTP. Responses to AMP and UMP were NO and endothelium dependent, whereas responses to ADP and UDP were NO and endothelium independent in the conduit arteries. RT-PCR showed expression of P2Y1, P2Y2, and P2Y4 receptors, but not P2Y6 receptors, in lung parenchyma, pulmonary arteries, and pulmonary artery endothelial cells. These data suggest that distinct P2Y receptors mediate the vasodilator responses to purine and pyrimidine nucleotides in the juvenile rabbit pulmonary circulation. ATP appears to cause NO-mediated vasodilation predominantly through P2Y2 receptors on endothelium.
A derivative-sigmoidal model reproduces operating point-dependent baroreflex neural arc transfer characteristics
Authors: Kawada Toru , Uemura Kazunori , Kashihara Koji , Kamiya Atsunori , Sugimachi Masaru , Sunagawa Kenji
Published: February 2004

A cascade model comprised of a derivative filter followed by a nonlinear sigmoidal component reproduces the input size dependence of transfer gain in the baroreflex neural arc from baroreceptor pressure input to efferent sympathetic nerve activity (SNA). We examined whether the same model could predict the operating point dependence of the baroreflex neural arc transfer characteristics estimated by a binary white noise input. In eight anesthetized rabbits, we isolated bilateral carotid sinuses from the systemic circulation and controlled intracarotid sinus pressure (CSP). We estimated the linear transfer function from CSP to SNA while varying mean CSP among 70, 100, 130, and 160 mmHg (P70, P100, P130, and P160, respectively). The transfer gain at 0.01 Hz was significantly smaller at P70 (0.61 ± 0.26) and P160 (0.60 ± 0.25) than at P100 (1.32 ± 0.42) and P130 (1.36 ± 0.45) (in arbitrary units/mmHg; means ± SD; P < 0.05). In contrast, transfer gain values above 0.5 Hz were similar among the protocols. As a result, the slope of increasing gain between 0.1 and 0.5 Hz was significantly steeper at P70 (17.6 ± 3.6) and P160 (14.1 ± 4.3) than at P100 (8.1 ± 4.4) and P130 (7.4 ± 6.6) (in dB/decade; means ± SD; P < 0.05). These results were consistent with those predicted by the derivative-sigmoidal model, where the deviation of mean input pressure from the center of the sigmoidal nonlinearity reduced the transfer gain mainly in the low-frequency range. The derivative-sigmoidal model functionally reproduces the dynamic SNA regulation by the arterial baroreflex over a wide operating range.
Suppression of electrical alternans by overexpression of HERG in canine ventricular myocytes
Authors: Hua Fei , Johns David C. , Gilmour Robert F.
Published: February 2004

Suppression of electrical alternans may be antiarrhythmic. Our previous computer simulations have suggested that increasing the rapid component of the delayed rectifier K+current ( IKr) suppresses alternans. To test this hypothesis, IKrin isolated canine ventricular myocytes was increased by infection with an adenovirus containing the gene for the pore-forming domain of IKr[human ether-a-go-go gene (HERG)]. With the use of the perforated or whole cell patch-clamp technique, action potentials recorded at different pacing cycle lengths (CLs) were applied to the myocytes as the command waveforms. HERG infection markedly increased peak IKrduring the action potential (from 0.54 ± 0.03 pA/pF in control to 3.60 ± 0.81 pA/pF). Rate-dependent alterations of peak IKrwere similar for freshly isolated myocytes and HERG-infected myocytes. In both cell types, IKrincreased when CL decreased from 1,000 to 500 ms and then decreased progressively as CL decreased further. During alternans at CL = 170 ms, peak IKrwas larger for the short than for the long action potential for both groups, but the difference in peak IKrwas larger for HERG-infected myocytes. The voltage at which peak IKroccurred was significantly less negative in HERG-infected myocytes, in association with shifts of the steady-state voltage-dependent activation and inactivation curves to less negative potentials. Pacing at short CL induced stable alternans in freshly isolated myocytes and in cultured myocytes without HERG infection, but not in HERG-infected myocytes. These data support the idea that increasing IKrmay be a viable approach to suppressing electrical alternans.
Influence of the glia limitans on pial arteriolar relaxation in the rat
Authors: Xu H. L. , Koenig H. M. , Ye S. , Feinstein D. L. , Pelligrino D. A.
Published: February 2004

We examined whether damage to the glia limitans (GL), via exposure to the gliotoxin l-α-aminoadipic acid (l-αAAA), alters hypercapnia-induced pial arteriolar dilation in vivo. Anesthetized female rats were prepared with closed cranial windows. Pial arteriolar diameters were measured using intravital microscopy. l-αAAA (2 mM) was injected into the space under the cranial windows 24 h before the study, and injury to the GL was confirmed by light microscopy. l-αAAA was associated with a reduction in pial arteriolar CO2 reactivity to 40–50% of the level seen in vehicle-treated controls, with no further reduction in the CO2 response after nitric oxide (NO) synthase (NOS) inhibition via Nω-nitro-l-arginine (l-NNA). Subsequent blockade of prostanoid synthesis, via indomethacin (Indo), reduced CO2 reactivity to 10–15% of normal. In vehicle-treated controls, l-NNA, followed by Indo, reduced the response to ∼50% and then to 15–20% of the normocapnic value, respectively. On the other hand, l-αAAA had no effect on vascular responses to the endothelium-dependent vasodilator acetylcholine or the NO donor SNAP and did not alter cortical somatosensory evoked responses. This indicates an absence of any direct l-αAAA actions on pial arterioles or influence on neuronal transmission. Furthermore, l-αAAA did not alter the vasodilation elicited by topical application of an acidic artificial cerebrospinal fluid solution, suggesting that the GL influences the pial arteriolar relaxation elicited by hypercapnic, but not local extracellular (EC), acidosis. That differences exist in the mechanisms mediating hypercapnia- versus EC acidosis-induced pial arteriolar dilations was further exemplified by the finding that topical application of a neuronal NOS (nNOS)-selective blocker (ARR-17477) reduced the response to hypercapnia (by ∼65%) but not the response to EC acidosis. Disruption of GL gap junctional communication, using an antisense oligodeoxynucleotide (ODN) connexin43 knockdown approach, was accompanied by a 33% lower CO2 reactivity versus missense ODN-treated controls. These results suggest that the GL contribution to the hypercapnic vascular response appears to involve the NO-dependent component rather than the prostanoid-dependent component and may involve gap junctional communication. We speculate that the GL may act to facilitate the spread, to pial vessels, of hypercapnia-induced vasodilating signals arising in the comparatively few scattered nNOS neurons that lie well beneath the GL.
Left atrial dilatation resulting from chronic mitral regurgitation decreases spatiotemporal organization of atrial fibrillation in left atrium
Authors: Everett Thomas H. , Verheule Sander , Wilson Emily E. , Foreman Scott , Olgin Jeffrey E.
Published: February 2004

Atrial conduction properties have been shown to differ among animal atrial fibrillation (AF) models of rapid atrial pacing (RAP), chronic mitral regurgitation (MR), and control. We hypothesized that these conduction differences would continue with the onset of AF, which would affect AF spatiotemporal organization, resulting in model-specific characteristics of AF. With frequency domain analysis of electrograms acquired from high-density optical mapping, AF from the right (RA) and left (LA) atrium in animals with RAP and MR were compared with control animals. At follow-up, the hearts were excised and perfused, and optical action potentials were recorded from a 2 × 2-cm area each of the RA and LA free wall with a 16 × 16 photodiode array. AF was induced with extra stimuli, several 2.4-s AF episodes were recorded in each dog, and a fast Fourier transform was calculated. The dominant frequency (DF) was determined, and the organization (organization index, OI) was calculated as the ratio of the area under the dominant peak and its harmonics to the total area of the spectrum. All possible pairs of electrograms for each episode were cross-correlated. LA AF in the chronic MR model showed an increase in the highest DF, the number of DF domains, and in frequency gradient compared with AF in control or RAP models. In addition, there was a decrease in OI and in the correlation coefficients in the LA of the MR model. These results suggest that the AF substrate in the MR model may be different from that of control or RAP models.
Insights into cardioprotection obtained from study of cellular Ca2+handling in myocardium of true hibernating mammals
Authors: Yatani Atsuko , Kim Song-Jung , Kudej Raymond K. , Wang Qian , Depre Christophe , Irie Keiichi , Kranias Evangelia G. , Vatner Stephen F. , Vatner Dorothy E.
Published: February 2004

Mammalian hibernators exhibit remarkable resistance to low body temperature, whereas nonhibernating (NHB) mammals develop ventricular dysfunction and arrhythmias. To investigate this adaptive change, we compared contractile and electrophysiological properties of left ventricular myocytes isolated from hibernating (HB) woodchucks ( Marmota monax) and control NHB woodchucks. The major findings of this study were the following: 1) the action potential duration in HB myocytes was significantly shorter than in NHB myocytes, but the amplitude of peak contraction was unchanged; 2) HB myocytes had a 33% decreased L-type Ca2+current ( ICa) density and twofold faster ICainactivation but no change in the current-voltage relationship; 3) there were no changes in the density of inward rectifier K+current, transient outward K+current, or Na+/Ca2+exchange current, but HB myocytes had increased sarcoplasmic reticulum Ca2+content as estimated from caffeine-induced Na+/Ca2+exchange current values; 4) expression of the L-type Ca2+channel α1C-subunit was decreased by 30% in HB hearts; and 5) mRNA and protein levels of sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a), phospholamban, and the Na+/Ca2+exchanger showed a pattern that is consistent with functional measurements: SERCA2a was increased and phospholamban was decreased in HB relative to NHB hearts with no change in the Na+/Ca2+exchanger. Thus reduced Ca2+channel density and faster ICainactivation coupled to enhanced sarcoplasmic reticulum Ca2+release may underlie shorter action potentials with sustained contractility in HB hearts. These changes may account for natural resistance to Ca2+overload-related ventricular dysfunction and point to an important cardioprotective mechanism during true hibernation.
Long-term treatment with cyclosporine decreases aquaporins and urea transporters in the rat kidney
Authors: Lim Sun-Woo , Li Can , Sun Bo-Kyung , Han Ki-Hwan , Kim Wan-Young , Oh Yoon-Wha , Lee Jong-Un , Kador Peter F. , Knepper Mark A. , Sands Jeff M. , Kim Jin , Yang Chul-Woo
Published: February 2004

The aim of this study was to evaluate the long-term effects of cyclosporine (CsA) treatment on urinary concentration ability. Rats were treated daily for 4 wk with vehicle (VH; olive oil, 1 ml/kg sc) or CsA (15 mg/kg sc). The influence of CsA on the kidney's ability to concentrate urine was evaluated using functional parameters and expression of aquaporins (AQP1–4) and of urea transporters (UT-A-1–3, and UT-B). Plasma vasopressin levels and the associated signal pathway were evaluated, and the effect of vasopressin infusion on urine concentration was observed in VH- and CsA-treated rats. Toxic effects of CsA on tubular cells in the medulla as well as the cortex were evaluated with aldose reductase (AR), Na-K-ATPase-α1expression, and by determining the number of terminal transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Long-term CsA treatment increased urine volume and fractional excretion of sodium and decreased urine osmolality and free-water reabsorption compared with VH-treated rats. These functional changes were accompanied by decreases in the expression of AQP (1–4) and UT (UT-A2, -A3, and UT-B), although there was no change in AQP2 in the cortex and outer medulla and UT-A1 in the inner medulla (IM). Plasma vasopressin levels were not significantly different between two groups, but infusion of vasopressin restored CsA-induced impairment of urine concentration. cAMP levels and Gsα protein expression were significantly reduced in CsA-treated rat kidneys compared with VH-treated rat kidneys. CsA treatment decreased the expression of AR and Na-K-ATPase-α1and increased the number of TUNEL-positive renal tubular cells in both the cortex and medulla. Moreover, the number of TUNEL-positive cells correlated with AQP2 or UT-A3) expression within the IM. In conclusion, CsA treatment impairs urine-concentrating ability by decreasing AQP and UT expression. Apoptotic cell death within the IM at least partially accounts for the CsA-induced urinary concentration defect.
Energetic cost of breathing, body composition, and pulmonary function in horses with recurrent airway obstruction
Authors: Mazan Melissa R. , Deveney Edward F. , DeWitt Shane , Bedenice Daniela , Hoffman Andrew
Published: February 2004

This study was conducted to determine whether horses with naturally occurring, severe chronic recurrent airway obstruction (RAO) 1) have a greater resting energy expenditure (REE) than control horses, 2) suffer body mass depletion, and 3) have significantly decreased REE after bronchodilation and, therefore, also 4) whether increased work of breathing contributes to the cachexia seen in some horses with RAO. Six RAO horses and six control horses underwent indirect calorimetric measures of REE and pulmonary function testing using the esophageal balloon-pneumotachograph method before and after treatment with ipratropium bromide, a parasympatholytic bronchodilator agent, at 4-h intervals for a 24-h period. Body condition scoring was performed, and an estimate of fat mass was determined via B-mode ultrasonography. O2and CO2fractions, respiratory airflow, respiratory rate, and pleural pressure changes were recorded, and O2consumption, CO2production, REE, pulmonary resistance, dynamic elastance, and tidal volume were calculated. In addition, we performed lung function testing and calorimetry both before and after sedation in two control horses. RAO horses had significantly lower body condition scores (2.8 ± 1.0 vs. 6.4 ± 1.2) and significantly greater O2consumption than controls (4.93 ± 1.30 vs. 2.93 ± 0.70 ml·kg−1·min−1). After bronchodilation, there was no significant difference in O2consumption between RAO horses and controls, although there remained evidence of residual airway obstruction. There was a strong correlation between O2consumption and indexes of airway obstruction. Xylazine sedation was not associated with changes in pulmonary function but did result in markedly decreased REE in controls.
Anatomic capillarization is maintained in relative excess of fiber oxidative capacity in some skeletal muscles of late middle-aged rats
Authors: Hepple Russell T. , Vogell Janis E.
Published: February 2004

The anatomic size of the capillary-to-fiber (C/F) interface plays an important role in O2 flux from blood to tissue by determining the surface area available for diffusion and is maintained in relative proportion to fiber mitochondrial volume across a wide range of muscle aerobic capacity. In the present study, we examined an estimate of the anatomic size of the C/F interface [the quotient of the individual C/F ratio and fiber perimeter, C/F perimeter exchange (CFPE) index] and fiber oxidative capacity in different skeletal muscles, or muscle regions, to test the hypothesis that capillarization would be maintained in relative excess of reduced fiber oxidative capacity in aged muscles. The right gastrocnemius, plantaris, and soleus muscles from young adult (8 mo old) and late middle-aged (28–30 mo old) Fischer 344 × Brown Norway F1 hybrid rats were excised for evaluation of flux through electron transport chain complexes I–III and/or morphometric estimation of capillarization. Muscle mass was lower in the gastrocnemius muscles of the older animals (2,076 ± 32 vs. 1,825 ± 47 mg in young adult vs. late middle-aged, respectively; mean ± SE) but not the plantaris or soleus muscles. Fibers were smaller in the white region of gastrocnemius muscles but larger in the red region of gastrocnemius muscles of the older animals. There was no difference in the number of capillaries around a fiber, the individual C/F ratio, or the CFPE index between groups for any muscle/region, whereas flux through complexes I–III was reduced by 29–43% in late middle-aged animals. Thus the greater quotient of indexes of anatomic capillarity (individual C/F ratio or CFPE index) and fiber oxidative capacity in soleus and the white region of gastrocnemius muscles, but not in the red region of gastrocnemius muscles of the older animals, shows that anatomic capillarity is maintained in relative excess of oxidative capacity in some muscle regions in late middle-aged rats.
Odorant Specificity of Single Olfactory Bulb Neurons to Amino Acids in the Channel Catfish
Authors: Nikonov Alexander A. , Caprio John
Published: February 2004

Odorant specificity to l-α-amino acids was determined for 245 olfactory bulb (OB) neurons recorded from 121 channel catfish. The initial tests included 4 amino acids representing acidic [monosodium glutamate (Glu)], basic [arginine (Arg)], and neutral [possessing short: alanine (Ala) and long: methionine (Met) side chains] amino acids that were previously indicated to bind to independent olfactory receptor sites. Ninety-one (37%) units (Group I) tested at 1, 10, and 100 μM showed high selectivity and were excited by only one of the 4 amino acids. Odorant specificity for the vast majority of Group I units did not change over the 3 s of response time analyzed. A total of 154 OB units (63%) (Group II) were excited by a second amino acid, but only at ≥10× odorant concentration. An additional 69 Group I units were tested with related amino acids and derivatives from 10−9 to 10−5 M to determine their excitatory odorant thresholds and selectivities. Two groups of units originally selective for Met were evident: those most sensitive to neutral amino acids having branched and linear side chains, respectively. OB units originally selective for Ala responded at low concentration to other similar amino acids. Units originally selective for Arg were excited at low concentration by amino acids possessing in their side chains at least 3 methylene groups and a terminal amide or guanidinium group. The specificities of the OB units determined electrophysiologically are sufficient to account for many of the previous results of behavioral discrimination of amino acids in this and related species.
Mitral and Tufted Cells Differ in the Decoding Manner of Odor Maps in the Rat Olfactory Bulb
Authors: Nagayama Shin , Takahashi Yuji K. , Yoshihara Yoshihiro , Mori Kensaku
Published: February 2004

Mitral and tufted cells in the mammalian olfactory bulb are principal neurons, each type having distinct projection pattern of their dendrites and axons. The morphological difference suggests that mitral and tufted cells are functionally distinct and may process different aspects of olfactory information. To examine this possibility, we recorded odorant-evoked spike responses from mitral and middle tufted cells in the aliphatic acid- and aldehyde-responsive cluster at the dorsomedial part of the rat olfactory bulb. Homologous series of aliphatic acids and aldehydes were used for odorant stimulation. In response to adequate odorants, mitral cells showed spike responses with relatively low firing rates, whereas middle tufted cells responded with higher firing rates. Examination of the molecular receptive range (MRR) indicated that most mitral cells exhibited a robust inhibitory MRR, whereas a majority of middle tufted cells showed no or only a weak inhibitory MRR. In addition, structurally different odorants that activated neighboring clusters inhibited the spike activity of mitral cells, whereas they caused no or only a weak inhibition in the middle tufted cells. Furthermore, responses of mitral cells to an adequate excitatory odorant were greatly inhibited by mixing the odorant with other odorants that activated neighboring glomeruli. In contrast, odorants that activated neighboring glomeruli did not significantly inhibit the responses of middle tufted cells to the adequate excitatory odorant. These results indicate a clear difference between mitral and middle tufted cells in the manner of decoding the glomerular odor maps.
Association between obesity and a prothrombotic state: the Framingham Offspring Study
Authors: Rosito Guido , D’Agostino Ralph , Massaro Joseph , Lipinska Izabella , Mittleman Murray , Sutherland Patrice , Wilson Peter , Levy Daniel , Muller James , Tofler Geoffrey
Published: February 2004

Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p<0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.
Platelet function in mitochondriopathy with stroke and stroke-like episodes
Authors: Finsterer Josef , Zellner Maria , Marsik Claudia , Dukic Tanja , Jilma Bernd , Kotzailias Nicole
Published: February 2004

Stroke and stroke-like episodes are frequent complications in mitochondriopathy, particulary in MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes) which is a disorder of the mitochondrial oxidative metabolism in diverse cell types. To clarify a possible pathological aspect of stroke in these patients, we investigated platelet function before and after physical exercise. Ten patients with mitochondriopathy and stroke and ten healthy sex and age matched controls were investigated in an analyst blinded, prospective cross-sectional trial. Exercise decreased intraplatelet adenosine triphosphate (ATP) concentrations by -22% from baseline in patients with mitochondriopathy (p<0.01 between groups) while exercise increased ATP-levels by 28% healthy controls (p=0.01 vs baseline). Thrombin receptor activating peptide (TRAP) stimulated P-selectin expression increased up to 50% (p<0.05) in healthy subjects following exercise compared to 39% (p>0.05) in patients with mitochondriopathy. Exercise trendwise decreased platelet plug formation under shear stress by 24% in patients as measured by the platelet function analyzer PFA-100®. Tromboelastography showed firm thrombus formation and delayed lysis in patients following exercise. In conclusion, this trial has shown that ATP depletion during and after exercise probably accounts for a defective oxidative metabolism in platelets of patients with mitochondriopathy and stroke. This might induce decreased platelet function in these patients but fails to explain the increased stroke rate. Therefore other mechanisms seem to be etiologically involved in the pathogenesis of stroke in patients with mitochondriopathy.