bluuebunny/crossref_metadata_2025 huggingface dataset:
Cosmological implications of a minimal length hypothesis
Authors: Ashoorioon A , Mann R B
Published: September 2006

One of the firm predictions of inflationary cosmology is the consistency relation between scalar and tensor spectra. It has been argued that such a relation — if experimentally confirmed — would offer strong support for the idea of inflation. We examine the possibility that trans-Planckian physics violates the consistency relation in the framework of inflation with a cutoff proposed in astro-ph/0009209. We find that despite the ambiguity that exists in choosing the action, Planck-scale physics modifies the consistency relation considerably. It also leads to the running of the spectral index. For modes that are larger than our current horizon, the tensor spectral index is positive. For a window of k values with amplitudes of the same order as the modes that are the precursors to structure formation, the behavior of the tensor spectral index is oscillatory about the standard Quantum field theory result, taking both positive and negative values. There is a hope that in the light of future experiments, this scenario of short distance physics, can be verified.PACS Nos.: 98.80.Cq , 98.80.-k, 98.80.Qc
Entanglement and adiabatic quantum computation
Authors: Ahrensmeier D
Published: September 2006

Adiabatic quantum computation provides an alternative approach to quantum computation using a time-dependent Hamiltonian. The time evolution of entanglement during the adiabatic quantum search algorithm is studied, and its relevance as a resource is discussed.PACS Nos.: 03.67.–a, 03.67.Lx, 03.67.Mn
Superresonance effect and energy flow in acoustic black holes
Authors: Kobes R
Published: September 2006

We study numerically the superresonance effect of scalar fields incident on an acoustic black hole. We show that the superresonance effect is quite large compared with the analogous effect in a Kerr black hole. We also do an analysis of the energy flow from these numerical solutions to determine where the outward flow of energy originates.PACS Nos.: 11.10.–z, 04.70.–s
Nuclear spectroscopy in the chaotic domain: level densities
Authors: French J B , Rab S , Smith J F , Haq R U , Kota V KB
Published: September 2006

In heavy nuclei, the structure generating the slow-neutron resonance spectrum extends downward in energy to ~(1–2) MeV excitation and, of course, upward as well until particle emission becomes significant, thereby generating an Embedded Gaussian Orthogonal Ensemble (EGOE) spectrum built on a secular mean-density function. In this extended chaotic domain, principles and methods for the calculation of one-point quantities (e.g., level densities, spin-cutoff factors, occupancies, etc.,) have been well developed during the last several years. The economy and the resultant generic forms follow from the dominance of unitary symmetries, central limit theorems, and quantum chaos. In this paper, techniques used for level densities are illustrated by a detailed study of several heavy nuclei, the input data being taken from the observed low-lying spectrum and the far-separated neutron-resonance spectrum, this in itself saying much about long-range spectral rigidity. Explicit forms for the interacting particle state densities, expectation values, and expectation-value densities of operators in Hamiltonian eigenstates are given. Extension of the formalism to two-point functions that deal with spectral fluctuations, transition strengths, and analysis of measures for broken symmetries and which involve the same formal structure is indicated; higher order correlation functions are of little immediate interest because they define quantities only rarely measurable.PACS Nos.: 21.10Ma, 21.60Cs, 24.60–k, 24.60.Lz
Factorization of the constants of motion
Authors: Nash P L , Chen L Y
Published: September 2006

A complete set of first integrals, or constants of motion, for a model system is constructed using “factorization”, as described below. The system is described by the effective Feynman Lagrangian L = [Formula: see text], with one of the simplest, nontrivial, potentials V(x) = (1/2)m ω2x2 selected for study. Four new, explicitly time-dependent, constants of the motion ci±, i = 1, 2 are defined for this system. While [Formula: see text]ci± ≠ 0, [Formula: see text]ci± = [Formula: see text]ci± + [Formula: see text]ci± + [Formula: see text]ci± + · · · = 0 along an extremal of L. The Hamiltonian H is shown to equal a sum of products of the ci±, and verifies [Formula: see text] = 0. A second, functionally independent constant of motion is also constructed as a sum of the quadratic products of ci±. It is shown that these derived constants of motion are in involution.PACS Nos.: 02.30.Jr, 02.30.Ik, 02.60.Cb, 02.30.Hq, 05.70.Ln, 02.50.–r
AN APPLICATION OF WELL-ORDERLY TREES IN GRAPH DRAWING
Authors: ZHANG HUAMING , HE XIN
Published: September 2006

Well-orderly tree is a powerful technique capable of deriving new results in graph encoding, graph enumeration and graph generation [3, 5]. In this paper, by using well-orderly trees, we prove that any plane graph G with n vertices has a visibility representation with height [Formula: see text], which can be constructed in linear time. This improves the best previous bound of [Formula: see text].
PACKING SOFT RECTANGLES
Authors: NAGAMOCHI HIROSHI
Published: September 2006

Let R be a rectangle with given area a(R), height h(R) and width w(R), and r1, r2, …, rn be n soft rectangles, where we mean by a soft rectangle a rectangle r whose area a(r) is prescribed but whose aspect ratio ρ(r) is allowed to be changed. In this paper, we consider the problem of packing n soft rectangles r1, r2, …, rn into R. We prove that, if a(R) ≥ Σ1≤i≤n a(ri) + 0.10103amax and amax ≤ 3( min {h(R), w(R)})2 hold for a amax = max 1≤i≤n a(ri), then these n soft rectangles can be packed inside R so that the apect ratio of each rectangle ri is at most 3.
ERRATA: "REPRESENTATION OF SEMIAUTOMATA BY CANONICAL WORDS AND EQUIVALENCES"
Authors: BRZOZOWSKI JANUSZ , JÜRGENSEN HELMUT
Published: September 2006

In the paper [1], Theorem 23 and Example 24 are incorrect. The corrected version is presented in this note.
QUANTUM DYNAMICAL SEMIGROUPS GENERATED BY NONCOMMUTATIVE UNBOUNDED ELLIPTIC OPERATORS
Authors: BAHN CHANGSOO , KO CHUL KI , PARK YONG MOON
Published: September 2006

We study quantum dynamical semigroups generated by noncommutative unbounded elliptic operators which can be written as Lindblad-type unbounded generators. Under appropriate conditions, we first construct the minimal quantum dynamical semigroups for the generators and then use Chebotarev and Fagnola's sufficient conditions for conservativity [1] to show that the semigroups are conservative. We then apply our results to a quantum mechanical system.
THE POSSIBLE JPCIG= 2++2+STATE X(1600)
Authors: WEI W. , ZHANG L. , ZHU SHI-LIN
Published: September 2006

The interesting state X(1600) with JPCIG= 2++2+cannot be a conventional [Formula: see text] meson in the quark model. Using a mixed interpolating current with different color configurations, we investigate the possible existence of X(1600) in the framework of QCD finite energy sum rules. Our results indicate that both the "hidden color" and coupled channel effects may be quite important in the multiquark system. We propose several reactions to look for this state.
AN INTERESTING MODEL OF QUANTAL TRANSMISSION
Authors: AHMED ZAFAR
Published: September 2006

We present the case of quantal transmission through a smooth, single-piece exponential potential, V(x) = -V0ex/a, in contrast to the piecewise continuous potentials, as an intersecting model to demonstrate the analytic extraction of transmission (reflection) coefficient. Several other aspects of quantal transmission are also discussed in this simple and exactly solvable model.
VARIABLE CHAPLYGIN GAS: CONSTRAINTS FROM CMBR ANDSNe Ia
Authors: SETHI GEETANJALI , SINGH SUSHIL K. , KUMAR PRANAV , JAIN DEEPAK , DEV ABHA
Published: September 2006

We constrain the parameters of the variable Chaplygin gas model, using the location of peaks of the CMBR spectrum and the SNe Ia "gold" data set. The equation of state of the model is P = -A(a)/ρ, where A(a) = A0a-nis a positive function of the cosmological scale factor a, A0and n> being constants. The variable Chaplygin gas interpolates from the dust-dominated era to the quintessence dominated era. The model is found to be compatible with current type Ia supernovae data and the location of the first peak if the values of Ωmand n lie in the interval [0.017, 0.117] and [-1.3, 2.6], respectively.
THE NUMERICAL SIMULATION OF PERTURBED ACCRETION DISK AROUND THE MASSIVE BLACK HOLE
Authors: DÖNMEZ ORHAN
Published: September 2006

The dynamical evolution of star–disk interaction containing a massive black hole is examined in a region in which physical perturbation dominates other processes and strong gravitational region dominates the potential. The numerical simulation of accretion disk around the black hole is modeled when star is captured by it. When the accretion disk, in steady state or not, is perturbed by the star, the disk around the black hole is destroyed by the star–disk interaction. Destroyed accretion disk creates a spiral shock wave and it causes loss of angular momentum. Finally, because of losing angular momentum, gas starts falling into the black hole. At the same time, X-ray is emitted by accretion disk during the unstable cases. The massive black hole may be created as a consequence of interaction.
Efficiency Considerations for Vertical kNN Text Categorisation
Authors: Rahal Imad , Najadat Hassan , Perrizo William
Published: September 2006

The importance of text mining stems from the availability of huge volumes of text databases holding a wealth of valuable information that needs to be mined. Text mining is a coarse area encompassing many finer branches one of which is text categorisation or text classification. Text categorisation is the process of assigning class labels to documents based entirely on their textual contents where we are given a document d, and asked to find its subject matter or class label, Ci.

In this paper, an optimised k-Nearest Neighbours classifier that uses discretisation, the P-tree technology, and dimensionality reduction to achieve a high degree of accuracy, space utilisation and time efficiency is proposed. One of the fundamental contributions of this work is that as new samples arrive, the proposed classifier can find the k nearest neighbours to the new sample from the training space without a single database scan.
Intranet and Knowledge Management: Putting the Cart Before the Horse?
Authors: Tanudjojo Satrijo , Braganza Ashley
Published: September 2006

This paper explores the use of intranet-technology to support knowledge intensive decision-making in a technical service delivery process of a major oilfield services company. Our findings show that creating, mobilising, and exchanging knowledge through a system which is based on intranet-technology delivers some forms of benefits to both the organisation and its clients, and helps in understanding what organisational knowledge is to be managed and the process of managing it defines the role of technology that enables knowledge management.
WAVELETS AND SPLINES FOR VERTICAL SCRATCH REMOVAL IN OLD MOVIE SEQUENCES
Authors: CIARLINI PATRIZIA , COSTANZO GIUSEPPE , LO CASCIO MARIA LAURA
Published: September 2006

In old movies, scratches are common damages that mostly result from a mechanical stress during the projection. A method for removing vertical scratches is proposed and suitable to be automatically applied to sequences of images. The method uses a wavelet decomposition of the original digital image, I, in order to separate the high frequency components and to elaborate corrupted data in the regular matrix, A, and in the vertical details matrix, V, only. For A, approximating functions are constructed in suitable spline spaces, which depend on the morphological quality of the image near the scratch. Monochromatic old images and images with simulated scratches have been considered to validate the method.
WAVELET RIESZ BASES IN THE SPACE ℓ2(ℤ)
Authors: PEVNYI A. B.
Published: September 2006

In this paper, the wavelet Riesz bases in the space ℓ2(ℤ) are studied. The main tool employed is discrete splines, which have received a considerable attention by many authors. The discrete splines are used for multiresolution analysis of the space ℓ2(ℤ).
WAVELET-HOUGH TRANSFORM WITH APPLICATIONS IN EDGE AND TARGET DETECTIONS
Authors: LI LUOQING , TANG YUAN Y.
Published: September 2006

In computer vision and image processing, edge detection concerns the localization of significant variations of the grey level image and the identification of the physical phenomena that originated them. It is difficult to design a general edge detection algorithm which performs well in many contexts and captures the requirements of subsequent processing stages. Consequently, over the history of digital image processing, a variety of edge detectors have been devised which differ in their mathematical and algorithmic properties. In this paper, we briefly describe some existing edge detectors. We investigate the wavelet transform with direction which is related to the Canny and Marr–Hildreth's edge detectors. This wavelet transform has a remarkable feature that plays an important role in image processing applications. We discuss its applications to edge and target detections. The direction effect enables the wavelets to analyze the directional features of images. Algorithms and experiments for edge and target detections have been developed based on the theory. And, very promising results have been shown in image processing.
INFLATION AND DEPLOYMENT SIMULATION OF RIGIDIZIBLE BEAM FOR LARGE DEPLOYABLE REFLECTORS
Authors: TAN HUIFENG , LANG MICHAEL , DATASHVILI LERI , BAIER HORST
Published: September 2006

The inflatable/rigidizable tube is a basic element for inflatable space structures. It can be made of carbon fabric/epoxy prepreg which includes a rigidizable epoxy resin and woven fabric. The fabric prepreg will be kept in prepreg state while stowed and then cured post deployment to be rigid in orbit. In this paper, a simple homogenized shear model of the fabric prepreg under inner pressure action is proposed to investigate shear modulus variation with the inner pressure; the dynamic inflation and deployment process of the fabric prepreg tube is simulated by LS-DYNA with airbag and multi-cavity model, and effects on deployment properties including inflation speed, material properties, and folder geometry are investigated.
FARMERS AS ENTREPRENEURS: DEVELOPING COMPETITIVE SKILLS
Authors: MCELWEE GERARD
Published: September 2006

The aim of this literature review is to consider the main issues derived from studies published on the subject of farmers' skills and entrepreneurial capacity to determine which topics have emerged as areas of research. This literature review analyzes the topics which have been the subject of farm entrepreneurship research and suggest that there are some limited emergent trends in the literature and that a number of key topics are receiving higher levels of attention than others: namely farm diversification and farmers' enterprise skills. Farming is not a homogeneous sector; farmers operate in a tightly constrained and regulated, complex and multi-faceted environment, which acts as a significant barrier to entrepreneurial activity.
C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment
Authors: Zebedin Eva , Mille Markus , Speiser Maria , Zarrabi Touran , Sandtner Walter , Latzenhofer Birgit , Todt Hannes , Hilber Karlheinz
Published: September 2006

Intracardiac transplantation of undifferentiated skeletal muscle cells (myoblasts) has emerged as a promising therapy for myocardial infarct repair and is already undergoing clinical trials. The fact that cells originating from skeletal muscle have different electrophysiological properties than cardiomyocytes, however, may considerably limit the success of this therapy and, in addition, cause side effects. Indeed, a major problem observed after myoblast transplantation is the occurrence of ventricular arrhythmias. The most often transient nature of these arrhythmias may suggest that, once transplanted into cardiac tissue, skeletal muscle cells adopt more cardiac-like electrophysiological properties. To test whether a cardiac cell environment can indeed modify electrophysiological parameters of skeletal muscle cells, we treated mouse C2C12 myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells. We found this treatment to significantly alter the activation and inactivation properties of sodium currents from “skeletal muscle” to more “cardiac”-like ones. Sodium currents of cardiac-conditioned cells showed a reduced sensitivity to block by tetrodotoxin. These findings and reverse transcription PCR experiments suggest that an upregulation of the expression of the cardiac sodium channel isoform Nav1.5 versus the skeletal muscle isoform Nav1.4 is responsible for the observed changes in sodium current function. We conclude that cardiomyocytes alter sodium channel isoform expression of skeletal muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more cardiac-like sodium current properties are generated.
Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction
Authors: Baber Syed R. , Deng Weiwen , Master Ryan G. , Bunnell Bruce A. , Taylor Bradley K. , Murthy Subramanyam N. , Hyman Albert L. , Kadowitz Philip J.
Published: September 2006

The administration of mesenchymal stem cells (MSCs) has been proposed for the treatment of pulmonary hypertension. However, the effect of intratracheally administered MSCs on the pulmonary vascular bed in monocrotaline-treated rats has not been determined. In the present study, the effect of intratracheal administration of rat MSCs (rMSCs) on monocrotaline-induced pulmonary hypertension and impaired endothelium-dependent responses were investigated in the rat. Intravenous injection of monocrotaline increased pulmonary arterial pressure and vascular resistance and decreased pulmonary vascular responses to acetylcholine without altering responses to sodium nitroprusside and without altering systemic responses to the vasodilator agents when responses were evaluated at 5 wk. The intratracheal injection of 3 × 106rMSCs 2 wk after administration of monocrotaline attenuated the rise in pulmonary arterial pressure and pulmonary vascular resistance and restored pulmonary responses to acetylcholine toward values measured in control rats. Treatment with rMSCs decreased the right ventricular hypertrophy induced by monocrotaline. Immunohistochemical studies showed widespread distribution of lacZ-labeled rMSCs in lung parenchyma surrounding airways in monocrotaline-treated rats. Immunofluorescence studies revealed that transplanted rMSCs retained expression of von Willebrand factor and smooth muscle actin markers specific for endothelial and smooth muscle phenotypes. However, immunolabeled cells were not detected in the wall of pulmonary vessels. These data suggest that the decrease in pulmonary vascular resistance and improvement in response to acetylcholine an endothelium-dependent vasodilator in monocrotaline-treated rats may result from a paracrine effect of the transplanted rMSCs in lung parenchyma, which improves vascular endothelial function in the monocrotaline-injured lung.
In silico assessment of Y1795C and Y1795H SCN5A mutations: implication for inherited arrhythmogenic syndromes
Authors: Vecchietti Stefania , Grandi Eleonora , Severi Stefano , Rivolta Ilaria , Napolitano Carlo , Priori Silvia G. , Cavalcanti Silvio
Published: September 2006

The effects of two SCN5A mutations (Y1795C, Y1795H), previously identified in one Long QT syndrome type 3 (LQT3) and one Brugada syndrome (BrS) families, were investigated by means of numerical modeling of ventricular action potential (AP). A Markov model capable of reproducing a wild-type as well as a mutant sodium current ( INa) was identified and was included into the Luo-Rudy ventricular cell model for action potential (AP) simulation. The characteristics of endocardial, midmyocardial, and epicardial cells were reproduced by differentiating the transient outward current ( ITO) and the ratio of slow delayed rectifier potassium ( IKs) to rapid delayed rectifier current ( IKr). Administration of flecainide and mexiletine was simulated by appropriately modifying INa, calcium current ( ICa), ITO, and IKr. Y1795C prolonged AP in a rate-dependent manner, and early afterdepolarizations (EADs) appeared during bradycardia in epicardial and midmyocardial cells; flecainide and mexiletine shortened AP and abolished EADs. Y1795H resulted in minimal changes in the APs; flecainide but not mexiletine induced APs heterogeneity across the ventricular wall that accounts for the ST segment elevation induced by flecainide in Y1795H carriers. The AP abnormalities induced by Y1795H and Y1795C can explain the clinically observed surface ECG phenotype. For the first time by modeling the effects of flecainide and mexiletine, we are able to gather mechanistic insights on the response to drugs administration observed in affected patients.
Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation despite endothelial dysfunction
Authors: Gendron Marie-Ève , Thorin-Trescases Nathalie , Villeneuve Louis , Thorin Eric
Published: September 2006

The endothelial function declines with age, and dyslipidemia (DL) has been shown to hasten this process by favoring the generation of reactive oxygen species (ROS). Cyclooxygenase-2 (COX-2) can be induced by ROS, but its contribution to the regulation of the endothelial function is unknown. Since COX-2 inhibitors may be deleterious to the cardiovascular system, we hypothesized that DL leads to ROS-dependent endothelial damage and a protective upregulation of COX-2. Dilations to acetylcholine (ACh) of renal arteries isolated from 3-, 6-, and 12-mo-old wild-type (WT) and DL mice expressing the human ApoB-100 were recorded with or without COX inhibitors and the antioxidant N-acetyl-l-cystein (NAC). Nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) were inhibited using Nω-nitro-l-arginine (l-NNA) and a depolarizing solution, respectively. In WT mice, the dilation to ACh declined at 12 mo but was insensitive to COX-1/2 inhibition alone or with NAC. DL led to an early endothelial dysfunction at 6 mo, normalized, however, by NAC. At 12 mo, vascular sensitivity to ACh was further reduced by DL. At this age, selective COX-2 inhibition reduced the dilation, whereas addition of NAC improved it. In 3- and 6-mo-old WT mice, l-NNA significantly reduced the dilation, whereas it limited the dilation only in 3-mo-old DL mice. EDHF-dependent dilation remains identical in both groups. These data suggest that COX-2 activity confers endothelium-dependent vasodilatory function in aged DL mice in the face of a pro-oxidative environment. Upregulation of this pathway compensates for the early loss of the contribution of NO in DL mice.
Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic mice
Authors: Subramanian Venkateswaran , Krishnamurthy Prasanna , Singh Krishna , Singh Mahipal
Published: September 2006

The purpose of this study was to investigate the role of osteopontin (OPN) in diabetic hearts. Diabetes was induced in wild-type (WT) and OPN knockout (KO) mice by using streptozotocin (150 mg/kg) injection. Left ventricular (LV) structural and functional remodeling was studied 30 and 60 days after induction of diabetes. Induction of diabetes increased OPN expression in cardiac myocytes. Heart weight-to-body weight ratio was increased in both diabetic (D) groups. Lung wet weight-to-dry weight ratio was increased only in the WT-D group. Peak left ventricular (LV) developed pressures measured using Langendorff perfusion analyses were reduced to a greater extent in WT-D versus KO-D group. LV end-diastolic pressure-volume curve exhibited a significant leftward shift in WT-D but not in KO-D group. LV end-diastolic diameter, percent fractional shortening, and the ratio of peak velocity of early and late filling (E/A wave) were significantly reduced in WT-D mice as analyzed by echocardiography. The increase in cardiac myocyte apoptosis and fibrosis was significantly higher in the WT-D group. Expression of atrial natriuretic peptide and transforming growth factor-β1 was significantly increased in the WT-D group. Induction of diabetes increased protein kinase C (PKC) phosphorylation in both groups. However, phosphorylation of PKC-βII was significantly higher in the WT-D group, whereas phosphorylation of PKC-ζ was significantly higher in the KO-D group. Levels of peroxisome proliferator-activated receptor-γ were significantly decreased in the WT-D group but not in the KO-D group. Thus increased expression of OPN may play a deleterious role during streptozotocin-induced diabetic cardiomyopathy with effects on cardiac fibrosis, hypertrophy, and myocyte apoptosis.
Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a computational model of human skeletal muscle
Authors: Gabhann Feilim Mac , Popel Aleksander S.
Published: September 2006

The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF121, VEGF165), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF165does not affect steady-state receptor binding. In the absence of neuropilin, VEGF121and VEGF165behave similarly, but neuropilin enhances the binding of VEGF165to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.
Biology of bone marrow-derived endothelial cell precursors
Authors: Schatteman Gina C. , Dunnwald Martine , Jiao Chunhua
Published: September 2006

Over the past decade, the old idea that the bone marrow contains endothelial cell precursors has become an area of renewed interest. While some still believe that there are no endothelial precursors in the blood, even among those who do, there is no consensus as to what they are or what they do. In this review, we describe the problems in identifying endothelial cells and conclude that expression of endothelial nitric oxide synthase may be the most reliable antigenic indicator of the phenotype. The evidence for two different classes of endothelial precursors is also presented. We suggest that, though there is no single endothelial cell precursor, we may be able to use these phenotypic variations to our advantage in better understanding their biology. We also discuss how a variety of genetic, epigenetic, and methodological differences can account for the seemingly contradictory findings on the physiological relevance of bone marrow-derived precursors in normal vascular maintenance and in response to injury. Data on the impact of tumor type and location on the contribution of bone marrow-derived cells to the tumor vasculature are also presented. These data provide hope that we may ultimately be able to predict those tumors in which bone marrow-derived cells will have a significant contribution and design therapies accordingly. Finally, factors that regulate bone marrow cell recruitment to and function in the endothelium are beginning to be identified, and several of these, including stromal derived factor 1, monocyte chemoattractant factor-1, and vascular endothelial growth factor are discussed.
The A2a/A2breceptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium
Authors: Lasley Robert D. , Kristo Gentian , Keith Byron J. , Mentzer Robert M.
Published: September 2006

There is increasing evidence for interactions among adenosine receptor subtypes in the brain and heart. The purpose of this study was to determine whether the adenosine A2areceptor modulates the infarct size-reducing effect of preischemic administration of adenosine receptor agonists in intact rat myocardium. Adult male rats were submitted to in vivo regional myocardial ischemia (25 min) and 2 h reperfusion. Vehicle-treated rats were compared with rats pretreated with the A1agonist 2-chloro- N6-cyclopentyladenosine (CCPA, 10 μg/kg), the nonselective agonist 5′- N-ethylcarboxamidoadenosine (NECA, 10 μg/kg), or the A2aagonist 2-[4-(2-carboxyethyl)phenethylamino]-5′- N-methylcarboxamidoadenosine (CGS-21680, 20 μg/kg). Additional CCPA- and NECA-treated rats were pretreated with the A1antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μg/kg), the A2a/A2bantagonist 4-(-2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a} {1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM-241385, 1.5 mg/kg) or the A3antagonist 3-propyl-6-ethyl-5[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523, 2 mg/kg). CCPA and NECA reduced myocardial infarct size by 50% and 35%, respectively, versus vehicle, but CGS-21680 had no effect. DPCPX blunted the bradycardia associated with CCPA and NECA, whereas ZM-241385 attenuated their hypotensive effects. Both DPCPX and ZM-241385 blocked the protective effects of CCPA and NECA. The A3antagonist did not alter the hemodynamic effects of CCPA or NECA, nor did it alter adenosine agonist cardioprotection. None of the antagonists alone altered myocardial infarct size. These findings suggest that although preischemic administration of an A2areceptor agonist does not induce cardioprotection, antagonism of the A2aand/or the A2breceptor blocks the cardioprotection associated with adenosine agonist pretreatment.
P-selectin-mediated adhesion impairs endothelium-dependent arteriolar dilation in hypercholesterolemic mice
Authors: Kim Min-ho , Carter Patsy R. , Harris Norman R.
Published: September 2006

Hypercholesterolemia is associated with an attenuation of endothelium-dependent dilation in arterioles and an increase in leukocyte and platelet adhesion in venules. The proximity of closely paired arterioles and venules is thought to facilitate heat and mass transport between the two and could be involved in transport of inflammatory and/or vasoactive mediators from venule to arteriole. In the current study, we tested the hypothesis that the impaired arteriolar dilation associated with hypercholesterolemia might be dependent on P-selectin-dependent blood cell adhesion in the closely paired venules. Leukocyte and platelet recruitment in venules and the endothelium-dependent response to bradykinin in second-order arterioles were observed in the mouse intestinal submucosa using intravital microscopy. Four weeks of a high-cholesterol diet decreased bradykinin-induced arteriolar dilation more dramatically in closely paired arterioles than in distantly paired arterioles. The dysfunctional arteriolar dilation of closely paired arterioles in hypercholesterolemic mice was significantly improved when the experiments were repeated in P-selectin-deficient mice (given the high-cholesterol diet) or in hypercholesterolemic mice injected with a P-selectin monoclonal antibody. A similar improvement in dilation of closely paired arterioles was attained in hypercholesterolemic mice given the superoxide dismutase mimetic Tempol. These findings indicate that hypercholesterolemia-induced increases in venular leukocyte and platelet adhesion might contribute to the impaired endothelium-dependent dilation of closely paired arterioles via a mechanism that is distance limited and dependent on P-selectin and superoxide.
Role of Cav1.2 L-type Ca2+channels in vascular tone: effects of nifedipine and Mg2+
Authors: Zhang Jin , Berra-Romani Roberto , Sinnegger-Brauns Martina J. , Striessnig Jõrg , Blaustein Mordecai P. , Matteson Donald R.
Published: September 2006

Ca2+entry via L-type voltage-gated Ca2+channels (LVGCs) is a key factor in generating myogenic tone (MT), as dihydropyridines (DHPs) and other LVGC blockers, including Mg2+, markedly reduce MT. Recent reports suggest, however, that elevated external Mg2+concentration and DHPs may also inhibit other Ca2+-entry pathways. Here, we explore the contribution of LVGCs to MT in intact, pressurized mesenteric small arteries using mutant mice (DHPR/R) expressing functional but DHP-insensitive Cav1.2 channels. In wild-type (WT), but not DHPR/R, mouse arteries, nifedipine (0.3–1.0 μM) markedly reduced MT and vasoconstriction induced by high external K+concentrations ([K+]o), a measure of LVGC-mediated Ca2+entry. Blocking MT and high [K+]o-induced vasoconstriction by <1 μM nifedipine in WT but not in DHPR/Rarteries implies that Ca2+entry via Cav1.2 LVGCs is obligatory for MT and that nifedipine inhibits MT exclusively by blocking LVGCs. We also examined the effects of Mg2+on MT and LVGCs. High external Mg2+concentration (10 mM) blocked MT, slowed the high [K+]o-induced vasoconstrictions, and decreased their amplitude in WT and DHPR/Rarteries. To verify that these effects of Mg2+are due to block of LVGCs, we characterized the effects of extracellular and intracellular Mg2+on LVGC currents in isolated mesenteric artery myocytes. DHP-sensitive LVGC currents are inhibited by both external and internal Mg2+. The results indicate that Mg2+relaxes MT by inhibiting Ca2+influx through LVGCs. These data provide new information about the central role of Cav1.2 LVGCs in generating and maintaining MT in mouse mesenteric small arteries.
TNF-α downregulates the leukotriene C4synthase gene in mononuclear phagocytes
Authors: Serio Kenneth J. , Luo Colin , Luo Linda , Mao Jenny T.
Published: September 2006

We studied the effect of tumor necrosis factor (TNF)-α exposure on cysteinyl leukotriene (LT) synthesis by cells of monocyte/macrophage lineage. TNF-α conditioning of monocytic THP-1 cells and primary human monocytes resulted in a decreased capacity for LTC4release. TNF-α exposure (for 16–24 h) decreased LTC4synthase mRNA in THP-1 cells, primary mouse bone marrow-derived macrophages, and eosinophilic AML14.3D10 cells. TNF-α downregulated LTC4synthase mRNA in THP-1 cells in a dose- and time-dependent manner, with downregulation observed as early as 4 h. The effect of TNF-α on LTC4synthase mRNA expression was mediated via the MEK/ERK pathway, but not via cyclooxygenase or nitric oxide synthase pathways. Conditioning of actinomycin D-treated cells with TNF-α did not accelerate degradation of LTC4synthase mRNA. TNF-α produced sustained activation of p50 and p65, which were previously reported by our group to decrease LTC4synthase promoter activity. In transiently transfected THP-1 cells, TNF-α decreased promoter activity via an element located within the first 620 bp of the promoter. We conclude that TNF-α exposure downregulates the synthetic capacity for cysteinyl LT release and LTC4synthase gene expression in monocytes/macrophages via a transcriptional mechanism.
Regulation of rat alveolar type 2 cell proliferation in vitro involves type II cAMP-dependent protein kinase
Authors: Samuelsen Jan T. , Schwarze Per E. , Huitfeldt Henrik S. , Thrane E. Vibeke , Låg Marit , Refsnes Magne , Skarpen Ellen , Becher Rune
Published: September 2006

To elucidate the role of cAMP and different cAMP-dependent protein kinases (PKA; A-kinase) in lung cell proliferation, we investigated rat alveolar type 2 cell proliferation in relation to activation or inhibition of PKA and PKA regulatory subunits (RIIα and RIα). Both the number of proliferating type 2 cells and the level of different regulatory subunits varied during 7 days of culture. The cells exhibited a distinct peak of proliferation after 5 days of culture. This proliferation peak was preceded by a rise in RIIα protein level. In contrast, an inverse relationship between RIα and type 2 cell proliferation was noted. Activation of PKA increased type 2 cell proliferation if given at peak RIIα expression. Furthermore, PKA inhibitors lowered the rate of proliferation only when a high RII level was observed. An antibody against the anchoring region of RIIα showed cell cycle-dependent binding in contrast to antibodies against other regions, possibly related to altered binding to A-kinase anchoring protein. Following activation of PKA, relocalization of RIIα was confirmed by immunocytochemistry. In conclusion, it appears that activation of PKA II is important in regulation of alveolar type 2 cell proliferation.
Inactivation of neuregulin-1 by nitration
Authors: Nethery David E. , Ghosh Sudakshina , Erzurum Serpil C. , Kern Jeffrey A.
Published: September 2006

Nitration is a posttranslational modification that can compromise protein function. We hypothesized that nitration of growth factors secreted in the lung may alter their interaction with their respective receptors and modulate the normal growth and differentiation program induced by ligand-receptor interaction. We tested this hypothesis in vitro by nitration of neuregulin-1's (NRG-1) EGF-like domain and studying the effect on NRG-1's activity. Nitration of NRG-1's (nNRG-1) EGF-like domain resulted in an inability to activate its receptor, the human epidermal growth factor receptors 2 and 3 (HER2/HER3) heterodimer, as defined by loss of HER2 tyrosine phosphorylation induced by nNRG-1 in MCF-7 cells. Receptor activation was not restored with increasing nNRG-1 concentration or exposure times. nNRG-1 did not compete with NRG-1 for HER2/HER3 binding in competition assays. In addition, nNRG-1 no longer induced proliferation of the MCF-7 cell line, as MCF-7 cells exposed to nNRG-1 and NRG-1 concurrently had the same proliferation rate as that induced by NRG-1 alone. Thus nitration of NRG-1's EGF-like domain caused it to lose its ability to bind and activate its receptor with loss of ligand-induced proliferation. Posttranslational nitration of growth factors in states where reactive nitrogen species are increased may be an important means of regulating growth factor receptor effects in the lung.
Intrapleural activation, processing, efficacy, and duration of protection of single-chain urokinase in evolving tetracycline-induced pleural injury in rabbits
Authors: Idell Steven , Allen Timothy , Chen Shande , Koenig Kathy , Mazar Andrew , Azghani Ali
Published: September 2006

Intrapleural fibrinolysins have been used to treat pleural loculations. However, the efficacy of clinically available agents has recently been questioned, providing a rationale for investigation of new interventions. Single-chain urokinase plasminogen activator resists inhibition by serpins, and repeated, daily intrapleural administration of this agent prevents intrapleural loculation more effectively than complexes of this proenzyme with its receptor (Idell S, Mazar A, Cines D, Kuo A, Parry G, Gawlak S, Juarez J, Koenig K, Azghani A, Hadden W, McLarty J, Miller E. Am J Respir Crit Care Med 166: 920–926, 2002). Understanding of the protective mechanism and intrapleural processing remains unclear. We speculated that single-chain urokinase could induce sustained local fibrinolysis and protection by selective administration either before, during, or following loculation after pleural injury induced by tetracycline in rabbits. Enzymography, immunoassays, histology, immunohistochemistry, morphology, and morphometry were used to test the efficacy, duration of protective effect, and processing of single-chain urokinase. Intrapleural single chain urokinase prevented loculation at 72 h after injury ( P < 0.01) if given either before or during adhesion formation and was converted to two-chain high-molecular-weight urokinase, which remained active for at least 24 h within pleural fluids. The effect was dose dependent, and established loculations at 72 h after tetracycline-induced injury were reversed at 96 h by single-dose treatment. Single-chain urokinase bound and saturated intrapleural plasminogen activator inhibitory (PAI)-1-like activity and urokinase-related immunoreactivity of the mesothelium was comparable in treatment or vehicle-control groups. Adhesions recurred by 2 wk after treatment with recurrence of excess local PAI activity. Single-chain urokinase induces sustained local fibrinolysis and reversibly prevents pleural loculation for up to 48 h after intrapleural administration after tetracycline-induced injury.
Expression and activity of cAMP phosphodiesterase isoforms in pulmonary artery smooth muscle cells from patients with pulmonary hypertension: role for PDE1
Authors: Murray Fiona , Patel Hemal H. , Suda Ryan Y. S. , Zhang Shen , Thistlethwaite Patricia A. , Yuan Jason X.-J. , Insel Paul A.
Published: September 2006

Pulmonary hypertension (PHT) is associated with increased vascular resistance due to sustained contraction and enhanced proliferation of pulmonary arterial smooth muscle cells (PASMC); the abnormal tone and remodeling in the pulmonary vasculature may relate, at least in part, to decreased cyclic nucleotide levels. Cyclic nucleotide phosphodiesterases (PDEs), of which 11 families have been identified, catalyze the hydrolysis of cAMP and cGMP. We tested the hypothesis that PASMC isolated from patients with PHT, either idiopathic pulmonary arterial hypertension (IPAH) or secondary pulmonary hypertension (SPH), have increased expression and activity of PDE isoforms that reduce the responsiveness of agents that raise cellular cAMP. Real-time PCR and immunoblotting demonstrated that the expression of PDE1A, PDE1C, PDE3B, and PDE5A was enhanced in PASMC from both IPAH and SPH patients compared with control PASMC. Consistent with this enhanced expression of PDEs, agonist-stimulated cAMP levels were significantly reduced in IPAH and SPH PASMC unless a PDE inhibitor was present. The use of specific PDE inhibitors revealed that an increase in PDE1 and PDE3 activity largely accounted for reduced agonist-induced cAMP levels and increased proliferation in IPAH and SPH PASMC. Treatment with PDE1C-targeted small interference RNA enhanced cAMP accumulation and inhibited cellular proliferation to a greater extent in PHT PASMC than controls. The results imply that an increase in PDE isoforms, in particular PDE1C, contributes to decreased cAMP and increased proliferation of PASMC in patients with PHT. PDE1 isoforms may provide novel targets for the treatment of both primary and secondary forms of the disease.
Regulation of airway smooth muscle α-actin expression by glucocorticoids
Authors: Goldsmith Adam M. , Hershenson Marc B. , Wolbert Miguel P. , Bentley J. Kelley
Published: September 2006

Airway smooth muscle hypertrophy appears to be present in severe asthma. However, the effect of corticosteroids on airway smooth muscle cell size or contractile protein expression has not been studied. We examined the effects of dexamethasone, fluticasone, and salmeterol on contractile protein expression in transforming growth factor (TGF)-β-treated primary bronchial smooth muscle cells. Dexamethasone and fluticasone, but not salmeterol, each reduced expression of α-smooth muscle actin and the short isoform of myosin light chain kinase. Steady-state α-actin mRNA level and stability were unchanged, consistent with posttranscriptional control. Fluticasone significantly decreased α-actin protein synthesis following treatment with the transcriptional inhibitor actinomycin D, indicative of an inhibitory effect on mRNA translation. Fluticasone also significantly increased α-actin protein turnover. Finally, fluticasone reduced TGF-β-induced incorporation of α-actin into filamentous actin, cell length, and cell shortening in response to ACh and KCl. We conclude that glucocorticoids reduce human airway smooth muscle α-smooth muscle actin expression and incorporation into contractile filaments, as well as contractile function, in part by attenuation of mRNA translation and enhancement of protein degradation.
Large-scale analysis of ion channel gene expression in the mouse heart during perinatal development
Authors: Harrell M. D. , Harbi S. , Hoffman J. F. , Zavadil J. , Coetzee W. A.
Published: September 2006

The immature and mature heart differ from each other in terms of excitability, action potential properties, contractility, and relaxation. This includes upregulation of repolarizing K+ currents, an enhanced inward rectifier K+ ( Kir) current, and changes in Ca2+, Na+, and Cl− currents. At the molecular level, the developmental regulation of ion channels is scantily described. Using a large-scale real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, we performed a comprehensive analysis of ion channel transcript expression during perinatal development in the embryonic (embryonic day 17.5), neonatal (postnatal days 1–2), and adult Swiss-Webster mouse hearts. These data are compared with publicly available microarray data sets (Cardiogenomics project). Developmental mRNA expression for several transcripts was consistent with the published literature. For example, transcripts such as Kir2.1, Kir3.1, Nav1.5, Cav1.2, etc. were upregulated after birth, whereas others [e.g., Ca2+-activated K+ (KCa)2.3 and minK] were downregulated. Cl− channel transcripts were expressed at higher levels in immature heart, particularly those that are activated by intracellular Ca2+. Defining alterations in the ion channel transcriptome during perinatal development will lead to a much improved understanding of the electrophysiological alterations occurring in the heart after birth. Our study may have important repercussions in understanding the mechanisms and consequences of electrophysiological alterations in infants and may pave the way for better understanding of clinically relevant events such as congenital abnormalities, cardiomyopathies, heart failure, arrhythmias, cardiac drug therapy, and the sudden infant death syndrome.