bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPLORING THE IMPACT OF CALENDAR EFFECTS ON THE DYNAMIC STRUCTURE AND FORECASTS OF FINANCIAL TIME SERIES
Authors: KYRTSOU CATHERINE , LEONTITSIS ALEXANDROS , SIRIOPOULOS COSTAS
Published: February 2006

Several recently developed chaotic forecasting methods give better results than the random walk forecasts. However they do not take into account specific regularities of stock returns reported in empirical finance literature, such as the calendar effects. In this paper, we present a method for filtering the day-of-the-week and the holiday effect in a time series. Our main objective is twofold. On the one hand we study how the underlying dynamics of the Nasdaq Composite, and TSE 300 Composite returns series can be influenced by the presence of calendar effects. On the other hand we adapt our method to chaotic forecasting. Its computational advantages lead to significant improvements of forecasts.
CLUSTER ANALYSIS FOR NON-GAUSSIAN LOCALLY STATIONARY PROCESSES
Authors: HIRUKAWA JUNICHI
Published: February 2006

Time series analysis under stationary assumption has been well established. However, stationary time series models are not plausible to describe the real world. Indeed, relatively long stretches of time series data should contain either slow or rapid changes in the spectra. To develop a general non-stationary theory, we have to pay careful attention to constituting a suitable model, otherwise the observations obtained in the future give no information about the present structure. Dahlhaus [1–4] has introduced an important class of non-stationary processes, called locally stationary processes which have the time varying spectral densities. In this paper, for a clustering problem of stock returns in Tokyo Stock Exchanges, we propose nonparametric approach based on generalized integral functional measures of the time varying spectral densities. The generalized measures include Gaussian Kullback–Leibler information and Chernoff information measures. The clustering results well extract the features of the relationship among the companies.
A NUMERICAL ANALYSIS OF THE EXTENDED BLACK–SCHOLES MODEL
Authors: ALBEVERIO SERGIO , POPOVICI ALEX , STEBLOVSKAYA VICTORIA
Published: February 2006

In this article some numerical results regarding the multidimensional extension of the Black–Scholes model introduced by Albeverio and Steblovskaya [1] (a multidimensional model with stochastic volatilities and correlations) are presented. The focus lies on aspects concerning the use of this model for the practice of financial derivatives. Two parameter estimation methods for the model using historical data from the market and an analysis of the corresponding numerical results are given. Practical advantages of pricing derivatives using this model compared to the original multidimensional Black–Scholes model are pointed out. In particular the prices of vanilla options and of implied volatility surfaces computed in the model are close to those observed on the market.
AN INFINITE FACTOR MODEL FOR CREDIT RISK
Authors: SCHMIDT THORSTEN
Published: February 2006

The defaultable term structure is modeled using stochastic differential equations in Hilbert spaces. This leads to an infinite dimensional model, which is free of arbitrage under a certain drift condition. Furthermore, the model is extended to incorporate ratings based on a Markov chain.
DIV–CURL TYPE THEOREM, H-CONVERGENCE AND STOKES FORMULA IN THE HEISENBERG GROUP
Authors: FRANCHI BRUNO , TCHOU NICOLETTA , TESI MARIA CARLA
Published: February 2006

In this paper, we prove a div–curl type theorem in the Heisenberg group ℍ1, and then we develop a theory of H-convergence for second order differential operators in divergence form in ℍ1. The div–curl theorem requires an intrinsic notion of the curl operator in ℍ1(that we denote by curlℍ), that turns out to be a second order differential operator in the left invariant horizontal vector fields. As an evidence of the coherence of this definition, we prove an intrinsic Stokes formula for curlℍ. Eventually, we show that this notion is related to one of the exterior differentials in Rumin's complex on contact manifolds.
POSITIVITY OF RICCI CURVATURE UNDER THE KÄHLER–RICCI FLOW
Authors: KNOPF DAN
Published: February 2006

In each complex dimension n ≥ 2, we construct complete Kähler manifolds of bounded curvature and non-negative Ricci curvature whose Kähler–Ricci evolutions immediately acquire Ricci curvature of mixed sign.
ADAPTIVE DESIGN FOR ESTIMATION OF MIXING HEIGHTS FROM SODAR BASED MEASUREMENTS
Authors: MUKHERJEE ABHIK , PAL PINAKPANI
Published: February 2006

Accurate estimation of mixing height is important, since it is an important parameter for lower atmospheric studies involving aerosol monitoring and pollutant dispersal models. Sodar happens to be one of the best instruments for monitoring the mixing height. But it suffers from the drawback of acoustic noise, which makes the measurement inaccurate. Conventional Kalman filter has been used to estimate atmospheric boundary layer by filtering the measurement noise involved in sodar data. But there are certain limitations of the accuracy available from conventional Kalman filter which may be overcome by proper adaptive design. The present work develops an adaptive scheme for estimation of mixing heights. It considers the selection of a proper meteorological system model from a bank of system models. Diurnal and seasonal changes in measurement noise statistics of the acoustic radar is taken into account by designing a fuzzy logic based adaptive scheme.
ACQUISITION OF SARSAT INFORMATION USING AN AUTO-CORRELATION BASED ADAPTIVE LINE ENHANCER
Authors: EL-KHAMY S. E. , HADHOUD M. M. , DESSOUKY M. I. , SALAM B. M. , ABD EL-SAMIE F. E.
Published: February 2006

This paper develops a new approach to the detection of the emergency locator transmitter (ELT) signal using an adaptive line enhancer (ALE). The input signal to the ALE is replaced by its autocorrelation function (ACF) because noise affects the central samples of the autocorrelation function only while it affects all samples of the noisy signal. This gives the ALE the ability to get rid of noise, easily. The output ACF is then used in the spectral estimation and detection of the ELT signal. This approach is related to the signal processing using Higher Order Statistics (HOS) since the ACF is the used input. The paper also compares the results of the new approach to other different previously used methods foe ELT signal detection. The first method uses the signal xk as an input to the ALE, and the second method uses [Formula: see text]. Results illustrate the superiority of the proposed method over the other two methods. A comparison study between the performance of two types of ALE; Fixed pole radius and variable pole radius ALEs in detecting the ELT signal, is introduced.
A ROBUST OPTICAL FLOW ESTIMATION UNDER VARYING ILLUMINATION
Authors: LU ZONGQING , XIE WEIXIN , PEI JIHONG
Published: February 2006

This paper proposes a new method for robust and accurate optical flow estimation. The robustness of the new method is the ability of weakening the disturbance of varying illumination and preserving motion boundaries. The significance of this work is twofold: In the first part the generalized dynamic image model (GDIM) is adopted based on gradient field to encourage robustness to non-uniform brightness variations; otherwise, a Bayesian selecting scheme is adopted to encourage the ability of preserving motion boundaries and reduce the error, bias generated by smoothness constraint. We validated our results on a set of real and synthetic sequences. The qualitative and quantitative results indicate that the new method produces more accurate and robust results, which better sustain our conclusions.
TESTING FOR INDEPENDENCE AND LRT FOR VAD
Authors: GÓRRIZ J. M. , PUNTONET C. G. , RAMÍREZ J.
Published: February 2006

In this paper we propose a simple method for Voice Activity Detection (VAD) in noisy environments based on periodogram of squares. The approach is based on a test for independence between a sequence of identically distributed random variables using the classical technique of Likelihood Ratio Test (LRT). This algorithm differs from many others in the way the decision rule is formulated (detection tests) and the domain used in this approach. Clear improvements in the speed of speech/non-speech discrimination accuracy demonstrate the effectiveness of the proposed VAD. It has been shown that application of statistical detection test leads to a better separation of the speech and noise distributions, thus allowing a more effective discrimination and a tradeoff between complexity and performance. The experimental analysis carried out on the AURORA databases and tasks provides an extensive performance evaluation together with an exhaustive comparison to the standard VADs such as ITU G.729, GSM AMR and ETSI AFE for distributed speech recognition (DSR), and other recently reported VADs based in statistical tests.
REAL TIME HARMONIC ESTIMATION BASED ON ARTIFICIAL NEURAL NETWORK, ETHERNET AND GPS TECHNOLOGY
Authors: HU ZHIJIAN , ZHANG CHENGXUE , FAN DAWEI , CHEN YUNPING
Published: February 2006

A new real time harmonic estimation approach based on adaptive neural network, GPS technology and distributed Ethernet is proposed in this paper. The method uses adaptive neural network to estimate the amplitudes and angles of the distorted current in power system. Only half-cycle harmonic current signal is used as the input of the neural network. In order to improve the accuracy of harmonic source identification, GPS (Global Positioning System) is used as the synchronization signal for the embedded measurement system based on digital signal processor (DSP). The sample selection and training methods of artificial neural network are explained and the hardware structure of the embedded harmonic identification system is given. RTDS (Real-Time Digital Simulator) simulation results illustrate the effectiveness of the proposed approach.
PROBABILISTIC NEURAL NETWORK AND ITS ADAPTIVE VERSION — A STOCHASTIC APPROACH TO PD PATTERN CLASSIFICATION TASK
Authors: KARTHIKEYAN B. , GOPAL S. , VENKATESH S.
Published: February 2006

The quality of electrical insulation of any power apparatus is an indispensable requirement for its successful and reliable operation. Partial Discharge (PD) phenomenon serves as an effective Non Destructive Testing (NDT) technique and provides an index on the quality of the insulation. The innovative trend of using Artificial Neural Network (ANN) towards the classification of PD patterns is cogent and discernible. In this paper a novel method for the classification of the PD patterns using the original Probabilistic Neural Network (PNN) as well as its variation is elucidated. A preprocessing scheme that extracts pertinent features of PD from the raw data towards achieving a compact ANN has been employed. The classification of single-type insulation defects such as voids, surface discharges and corona has been taken up. The first part of the paper gives a brief on PD, various diagnostic techniques and interpretation. The second part deals with the theoretical concepts of PNN and its adaptive version. The last part provides details on various results and comparisons of the PNN and its adaptive version in PD pattern classification.
WEB INFORMATION ACQUISITION BY PERSONAL SEARCH ENGINE BASED ON SVM
Authors: WANG RUJING , WANG DEJI
Published: February 2006

The quantity of web information is growing exponentially with time, and the challenge of acquiring information efficiently by personal search engine is increasingly complex. Personal preference is not easily described but can be observed from the examples given. Supervised Clustering with Support Vector Machines have been introduced to learn personal preference, however, it is not specialized and cannot be applied to the domain knowledge. In this paper, we introduce the ontology and semantic similarity into SVM as similar measurement. Experiments on agricultural information acquisition validate that it is highly effective.
Quaternary fans and terraces in the Khumbu Himal south of Mount Everest: their characteristics, age and formation
Authors: Barnard Patrick L. , Owen Lewis A. , Finkel Robert C.
Published: February 2006

Large fans and terraces are frequent in the Khumbu Himal within the high Himalayan valleys south of Mt. Everest. These features are composed of massive matrix- and clast-supported diamicts that were formed from both hyperconcentrated flows and coarse-grained debris flows. Cosmogenic radionuclide (CRN) exposure ages for boulders on fans and terraces indicate that periods of fan and terrace formation occurred at
c
. 16,
c
. 12,
c
. 8,
c
. 4 and
c
. 1.5 ka, and are broadly coincident with the timing of glaciation in the region. The dating precision is insufficient to resolve whether the surfaces formed before, during or after the correlated glacial advance. However, the sedimentology, and morphostratigraphic and geomorphological relationships suggest that fan and terrace sedimentation in this part of the Himalaya primarily occurs during glacier retreat and is thus paraglacial in origin. Furthermore, modern glacial-lake outburst floods and their associated deposits are common in the Khumbu Himal as the result of glacial retreat during historical times. We therefore suggest that Late Quaternary and Holocene fan and terrace formation and sediment transfer are probably linked to temporal changes in discharge and sediment load caused by glacier oscillations responding to climate change. The timing of major sedimentation events in this region can be correlated with fans and terraces in other parts of the Himalaya, suggesting that major sedimentation throughout the Himalaya is synchronous and tied to regional climatic oscillations. Bedrock incision rates calculated from strath terrace ages average
c
. 3.9 mm a
−1
, suggesting that the overall rate of incision is set by regional uplift.
Early Silurian mafic–ultramafic and granitic plutonism in contemporaneous flysch, Magerøy, northern Norway: U–Pb ages and regional significance
Authors: Corfu F. , Torsvik T.H. , Andersen T.B. , Ashwal L.D. , Ramsay D.M. , Roberts R.J.
Published: February 2006

The Caledonian Magerøy sequence comprises Earliest Silurian clastic metasedimentary rocks, which underwent folding and regional metamorphism and were intruded by a mafic–ultramafic complex and various granitic plutons. U–Pb ages of 438.2 ± 0.7 Ma for gabbro in the Honningsvåg Igneous Complex, 438.4 ± 0.9 Ma for an associated granite and 437.7 ± 1.6 Ma for the Finnvik granite coincide within error with the age of deposition inferred from fossils demonstrating a very rapid geological evolution. Plutons of peraluminous affinity are somewhat younger at 436.0 ± 1.0 Ma (Skarsvåg granite) and 434.5 ± 1.5 Ma (a granitic dyke in the Skarsvåg Nappe). The association of flysch deposition, folding and mafic–felsic magmatism suggests formation at a trench–ridge intersection. These Early Silurian events are the expression of a period of major magmatism in a variety of settings all along the Caledonides, probably reflecting rapid convergence and subduction during closure of the Iapetus Ocean. Re-evaluation of the palaeomagnetic signature of the Honningsvåg Igneous Complex indicates that at the time of formation the suite was located in an equatorial position, probably close to the Laurentian margin, and was subsequently translated southward by some 1350 km prior to and during emplacement onto the Baltic margin.
Methodology for delineating groundwater protection areas against persistent contaminants
Authors: Bussard T. , Tacher L. , Parriaux A. , Maître V.
Published: February 2006

This study proposes a general methodology, applied in Switzerland, for the delineation of protection areas for abstracted groundwater against persistent chemical contaminants in order to establish: (1) remediation programmes in the event of contamination and (2) prevention programmes, in a general way.

This new approach is based on the complete groundwater flow cycle, from the surface of the catchment zone to the groundwater source itself; areas with the highest contribution rate to the groundwater source will be preferentially protected. The method under consideration thus provides a tool for sustainable development and land management.

To date, four actual cases have been treated in order to test the method's applicability. The results are convincing in various porous or fractured aquifers. One case is presented to illustrate an application of the methodology.
UK Chalk Group stratigraphy (Cenomanian – Santonian) determined from borehole geophysical logs
Authors: Woods M.A.
Published: February 2006

Borehole geophysical logs through the Chalk Group of SE England have distinctive profiles that correspond with formational boundaries, recognized by lithological changes in borehole core and mapped by the British Geological Survey on the basis of lithology and topographic features at outcrop. Borehole geophysics graphically demonstrates the validity of the stratigraphy of the Chalk Group used by the British Geological Survey, and can be used to refute recent arguments against lithostratigraphical subdivision of the White Chalk Subgroup. Although intra-formational changes in the detail of borehole geophysical logs may occur between regions, generalized trends can still be used for inter-regional recognition of formations in the subsurface. Much previous work has focused on the utility of borehole geophysics for marker-bed recognition and correlation in the Chalk Group, but little attention has been paid to the more fundamental task of characterizing formations. This approach allows a much greater appreciation of regional Chalk Group stratigraphy than might be evident from available outcrops, and is the first step in the development of three-dimensional digital geological models of the Chalk Group.
Strength, durability and cost effectiveness of cement-stabilized laterite hollow blocks
Authors: Alutu O.E. , Oghenejobo A.E.
Published: February 2006

Strength and durability of cement-stabilized laterite hollow blocks made with laterite soils at three different locations in Edo State were studied. To this end, blocks were produced with water content at about the optimum moisture with varying percentages of cement from 3% to 15% at 2% increments and compactive pressures ranging from 3.44 N/mm
2
to 17.20 N/mm
2
. The result showed that for 7% cement content and 13.76 N/mm
2
compactive pressure, blocks of strength of at least 2.0N/mm
2
at 28 days, could be produced. The blocks showed no features of wear after exposure to rain with weight losses within permissible limits after 12-cycles of wetting-brushing-drying. Cost analysis showed that laterite blocks have 40% cost advantage over similar sandcrete blocks.
Foxl1-deficient mice exhibit aberrant epithelial cell positioning resulting from dysregulated EphB/EphrinB expression in the small intestine
Authors: Takano-Maruyama Masumi , Hase Koji , Fukamachi Hiroshi , Kato Yasutaka , Koseki Haruhiko , Ohno Hiroshi
Published: February 2006

The winged helix transcription factor Foxl1, expressed in the gut mesenchyme, regulates epithelial cell proliferation and differentiation through the Wnt/β-catenin pathway. To better understand the role of Foxl1 in epithelial morphogenesis, we examined the tissue structure and positioning of epithelial cells in the small intestine of Foxl1-deficient mice. The small intestine of Foxl1-deficient mice manifested aberrant crypt structure, including widely distributed Paneth cells, which coincided with the ectopic and increased expression of EphB2 and EphB3, which are key regulators of epithelial cell positioning. Furthermore, real-time quantitative PCR indicated that a subset of Wnt family genes was highly expressed in the gut mesenchyme of Foxl1-deficient mice compared with that of wild-type mice. Such an increase in Wnt expression was remarkable in the mesenchyme, where the aberrant Paneth cell positioning was observed by in situ hybridization. Foxl1 plays an important role in the maintenance of crypt architecture and epithelial cell positioning through the mesenchymal-epithelial interaction in the small intestine. This interaction is essential for the normal regulation of the Wnt/β-catenin pathway and the subsequent EphB/EphrinB expression.
Different effects of endotoxic shock on the respiratory function of liver and heart mitochondria in rats
Authors: Kozlov Andrey V. , Staniek Katrin , Haindl Susanne , Piskernik Christina , Öhlinger Wolfgang , Gille Lars , Nohl Hans , Bahrami Soheyl , Redl Heinz
Published: February 2006

This study was designed to clarify whether mitochondrial function/dysfunction and reactive oxygen species (ROS) production have a temporal relationship with organ failure during endotoxic shock. Adult male Sprague-Dawley rats were divided into three groups receiving 1) isotonic saline (control group, n = 16); 2) 8 mg/kg lipopolysaccharide (LPS; n = 8); or 3) 20 mg/kg LPS ( n = 8) intraperitoneally under short anesthesia with 3.5% of isoflurane. After 16 h, animals were killed to analyze plasma, rat liver mitochondria (RLM), and rat heart mitochondria (RHM). In accordance with plasma analysis, LPS-treated rats were divided into “responders” and “nonresponders” with high and low levels of alanine aminotransferase and creatine, respectively. RHM from responders had significantly lower respiratory activity in state 3, suggesting a decreased rate of ATP synthesis. In contrast, RLM from responders had significantly higher respiratory activity in state 3 than both nonresponders and the control group. This increase was accompanied by a decrease in phosphate-to-oxygen ratio values, which was not observed in RHM. ROS generation determined with a spin probe, 1-hydroxy-3-carboxypyrrolidine, neither revealed a difference in RHM between LPS and control groups nor between responders and nonresponders. In contrast, RLM isolated from responders showed a marked increase in ROS production compared with both the control group and nonresponders. Our data demonstrate that 1) RHM and RLM respond to endotoxic shock in a different manner, decreasing and increasing respiratory activity, respectively, and 2) there is a temporal relationship between ROS production in RLM (but not in RHM) and tissue damage in rats subjected to LPS shock.
Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep
Authors: Mita Sachiko , Suzuki Hiroshi , Akita Hidetaka , Hayashi Hisamitsu , Onuki Reiko , Hofmann Alan F. , Sugiyama Yuichi
Published: February 2006

Na+-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a Kmvalue of 20 μM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.
Ghrelin acts on the dorsal vagal complex to stimulate pancreatic protein secretion
Authors: Li Ying , Wu Xiaoyin , Zhao Ying , Chen Shengliang , Owyang Chung
Published: February 2006

Ghrelin receptors are present in the central nervous system. We hypothesized that ghrelin released from the stomach acts as an endocrine substance and stimulates brain stem vagovagal circuitry to evoke pancreatic secretion. In an in vivo anesthetized rat model, an intravenous infusion of ghrelin at doses of 5, 10, and 25 nmol increased pancreatic protein secretion from a basal level of 125 ± 6 to 186 ± 8, 295 ± 12, and 356 ± 11 mg/h, respectively. Pretreatment with atropine or hexamethonium or an acute vagotomy, but not a perivagal application of capsaicin, completely abolished pancreatic protein secretion responses to ghrelin. In conscious rats, an intravenous infusion of ghrelin at a dose of 10 nmol resulted in a 2.2-fold increase in pancreatic protein secretion over basal volume. Selective ablation of the area postrema abolished pancreatic protein secretion stimulated by intravenous infusion of ghrelin but did not alter the increase in pancreatic protein secretion evoked by diversion of bile-pancreatic juice. Immunohistochemical staining showed a marked increase in the number of c-Fos-expressing neurons in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus after an intravenous infusion of ghrelin in sham-lesioned rats; selective ablation of the area postrema eliminated this increase. In conclusion, ghrelin stimulates pancreatic secretion via a vagal cholinergic efferent pathway. Circulating ghrelin gains access to the brain stem vagovagal circuitry via the area postrema, which represents the primary target on which peripheral ghrelin may act as an endocrine substance to stimulate pancreatic secretion.
Epoxyeicosatrienoic acids in cardioprotection: ischemic versus reperfusion injury
Authors: Nithipatikom Kasem , Moore Jeannine M. , Isbell Marilyn A. , Falck John R. , Gross Garrett J.
Published: February 2006

Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce increases in postischemic function via ATP-sensitive potassium channels (KATP); however, the direct effects of EETs on infarct size (IS) have not been investigated. We demonstrate that two major regioisomers of CYP epoxygenases, 11,12-EET and 14,15-EET, significantly reduced IS in dogs compared to control (22.1 ± 1.8%), whether administered 15 min before 60 min of coronary occlusion (6.4 ± 1.9%, 11,12-EET; and 8.4 ± 2.4%, 14.15-EET) or 5 min before 3 h of reperfusion (8.8 ± 2.1%, 11,12-EET; and 9.7 ± 1.4%, 14,15-EET). Pretreatment with the epoxide hydrolase metabolite of 14,15-EET, 14,15-dihydroxyeicosatrienoic acid, had no effect. The protective effect of 11,12-EET was abolished (24.3 ± 4.6%) by the KATP channel antagonist glibenclamide. Furthermore, one 5-min period of ischemic preconditioning (IPC) reduced IS to a similar extent (8.7 ± 2.8%) to that observed with the EETs. The selective CYP epoxygenase inhibitor, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH), did not block the effect of IPC. However, administration of MS-PPOH concomitantly with N-methylsulfonyl-12,12-dibromododec-11-enanide (DDMS), a selective inhibitor of endogenous CYP ω-hydroxylases, abolished the reduction in myocardial IS expressed as a percentage of area at risk (IS/AAR) produced by DDMS (4.6 ± 1.2%, DDMS; and 22.2 ± 3.4%, MS-PPOH + DDMS). These data suggest that 11,12-EET and 14,15-EET produce reductions in IS/AAR primarily at reperfusion. Conversely, inhibition of CYP epoxygenases and endogenous EET formation by MS-PPOH, in the presence of the CYP ω-hydroxylase inhibitor DDMS blocked cardioprotection, which suggests that endogenous EETs are important for the beneficial effects observed when CYP ω-hydroxylases are inhibited. Finally, the protective effects of EETs are mediated by cardiac KATP channels.
Alterations in structure and mechanics of resistance arteries from ouabain-induced hypertensive rats
Authors: Briones Ana M. , Xavier Fabiano E. , Arribas Silvia M. , González M. Carmen , Rossoni Luciana V. , Alonso María J. , Salaices Mercedes
Published: February 2006

We have previously described that chronic administration of ouabain induces hypertension and functional alterations in mesenteric resistance arteries. The aim of this study was to analyze whether ouabain treatment also alters the structural and mechanical properties of mesenteric resistance arteries. Wistar rats were treated for 5 wk with ouabain (8.0 μg/day sc). The vascular structure and mechanics of the third-order branches of the mesenteric artery were assessed with pressure myography and confocal microscopy. Total collagen content was determined by picrosirius red staining, collagen I/III was analyzed by Western blot, and elastin was studied by confocal microscopy. Vascular reactivity was analyzed by wire myography. Internal and external diameters and cross-sectional area were diminished, whereas the wall-to-lumen ratio was increased in arteries from ouabain-treated rats compared with controls. In addition, arteries from ouabain-treated rats were stiffer. Ouabain treatment decreased smooth muscle cell number and increased total and I/III collagens in the vascular wall. However, this treatment did not modify adventitia and media thickness, nuclei morphology, elastin structure, and vascular reactivity to norepinephrine and acetylcholine. The present work shows hypotrophic inward remodeling of mesenteric resistance arteries from ouabain-treated rats that seems to be the consequence of a combination of decreased cell number and impaired distension of the artery, possibly due to a higher stiffness associated with collagen deposition. The narrowing of resistance arteries could play a role in the pathogenesis of hypertension in this model.
Cigarette smoke induces proinflammatory cytokine release by activation of NF-κB and posttranslational modifications of histone deacetylase in macrophages
Authors: Yang Se-Ran , Chida Asiya S. , Bauter Mark R. , Shafiq Nusrat , Seweryniak Kathryn , Maggirwar Sanjay B. , Kilty Iain , Rahman Irfan
Published: February 2006

Cigarette smoke-mediated oxidative stress induces an inflammatory response in the lungs by stimulating the release of proinflammatory cytokines. Chromatin remodeling due to histone acetylation and deacetylation is known to play an important role in transcriptional regulation of proinflammatory genes. The aim of this study was to investigate the molecular mechanism(s) of inflammatory responses caused by cigarette smoke extract (CSE) in the human macrophage-like cell line MonoMac6 and whether the treatment of these cells with the antioxidant glutathione (GSH) monoethyl ester, or modulation of the thioredoxin redox system, can attenuate cigarette smoke-mediated IL-8 release. Exposure of MonoMac6 cells to CSE (1% and 2.5%) increased IL-8 and TNF-α production vs. control at 24 h and was associated with significant depletion of GSH levels associated with increased reactive oxygen species release in addition to activation of NF-κB. Inhibition of IKK ablated the CSE-mediated IL-8 release, suggesting that this process is dependent on the NF-κB pathway. CSE also reduced histone deacetylase (HDAC) activity and HDAC1, HDAC2, and HDAC3 protein levels. This was associated with posttranslational modification of HDAC1, HDAC2, and HDAC3 protein by nitrotyrosine and aldehyde-adduct formation. Pretreatment of cells with GSH monoethyl ester, but not thioredoxin/thioredoxin reductase, reversed cigarette smoke-induced reduction in HDAC levels and significantly inhibited IL-8 release. Thus cigarette smoke-induced release of IL-8 is associated with activation of NF-κB via IKK and reduction in HDAC levels/activity in macrophages. Moreover, cigarette smoke-mediated proinflammatory events are regulated by the redox status of the cells.
Metabolomic profiling of heat stress: hardening and recovery of homeostasis in Drosophila
Authors: Malmendal Anders , Overgaard Johannes , Bundy Jacob G. , Sørensen Jesper G. , Nielsen Niels Chr. , Loeschcke Volker , Holmstrup Martin
Published: February 2006

Frequent exposure of terrestrial insects to temperature variation has led to the evolution of protective biochemical and physiological mechanisms, such as the heat shock response, which markedly increases the tolerance to heat stress. Insight into such mechanisms has, so far, mainly relied on selective studies of specific compounds or characteristics or studies at the genomic or proteomic levels. In the present study, we have used untargeted NMR metabolomic profiling to examine the biological response to heat stress in Drosophila melanogaster. The metabolite profile was analyzed during recovery after exposure to different thermal stress treatments and compared with untreated controls. Both moderate and severe heat stress gave clear effects on the metabolite profiles. The profiles clearly demonstrated that hardening by moderate heat stress led to a faster reestablishment of metabolite homeostasis after subsequent heat stress. Several metabolites were identified as responsive to heat stress and could be related to known physiological and biochemical responses. The time course of the recovery of metabolite homeostasis mirrored general changes in gene expression, showing that recovery follows the same temporal pattern at these two biological levels. Finally, our data show that heat hardening permits a quicker return to homeostasis, rather than a reduction of the acute metabolic perturbation and that the reestablishment of homeostasis is important for obtaining maximal heat-hardening effect. The results display the power of NMR metabolomic profiling for characterization of the instantaneous physiological condition, enabling direct visualization of the perturbation of and return to homeostasis.
Chronic hypoxic decreases in soluble guanylate cyclase protein and enzyme activity are age dependent in fetal and adult ovine carotid arteries
Authors: Williams James M. , White Charles R. , Chang Melody M. , Injeti Elisha R. , Zhang Lubo , Pearce William J.
Published: February 2006

The present study tests the hypothesis that chronic hypoxia enhances reactivity to nitric oxide (NO) through age-dependent increases in soluble guanylate cyclase (sGC) and protein kinase G (PKG) activity. In term fetal and adult ovine carotids, chronic hypoxia had no significant effect on mRNA levels for the β1-subunit of sGC, but depressed sGC abundance by 16% in fetal and 50% in adult arteries, through possible depression of rates of mRNA translation (15% in fetal and 50% in adult) and/or increased protein turnover. Chronic hypoxia also depressed the catalytic activity of sGC, but only in fetal arteries (63%). Total sGC activity was reduced by chronic hypoxia in both fetal (69%) and adult (37%) carotid homogenates, but this effect was not observed in intact arteries when sGC activity was measured by timed accumulation of cGMP. In intact arteries treated with 300 μM 3-isobutyl-1-methylxanthine (IBMX), chronic hypoxia dramatically enhanced sGC activity in fetal (186%) but not adult (89%) arteries. This latter observation suggests that homogenization either removed an sGC activator, released an sGC inhibitor, or altered the phosphorylation state of the enzyme, resulting in reduced activity. In the absence of IBMX, chronic hypoxia had no significant effect on rates of cGMP accumulation. Chronic hypoxia also depressed the ability of the cGMP analog, 8-( p-chlorophenylthio)-cGMP, to promote vasorelaxation in both fetal (8%) and adult (12%) arteries. Together, these results emphasize the fact that intact and homogenized artery studies of sGC activity do not always yield equivalent results. The results further suggest that enhancement of reactivity to NO by chronic hypoxia must occur upstream of PKG and can only be possible if changes in cGMP occurred in functional compartments that afforded either temporal or chemical protection to the actions of phosphodiesterase. The range and age dependence of hypoxic effects observed also suggest that some responses to hypoxia must be compensatory and homeostatic, with reactivity to NO as the primary regulated variable.
The weight loss elicited by cobalt protoporphyrin is related to decreased activity of nitric oxide synthase in the hypothalamus
Authors: Li Muyao , Vizzard Margaret A. , Jaworski Diane M. , Galbraith Richard A.
Published: February 2006

Administration of cobaltic protoporphyrin IX (CoPP) into the third ventricle of the brain by intracerebroventricular injection in rodents is known to result in transient hypophagia and remarkably prolonged weight loss. The mechanism of action of CoPP in eliciting these effects is unknown. It is known that nitric oxide plays a role in food intake and that the hyperphagia that results from a wide variety of genetic, physiological, and pharmacological stimuli can be blocked by the administration of inhibitors of the enzyme nitric oxide synthase (NOS). We demonstrate that intracerebroventricular administration of compounds that alter nitrergic tone can also change food ingestion and weight gain patterns in normophagic rats. We also demonstrate that CoPP decreases NOS activity but that it paradoxically increases neuronal NOS transcript expression and increases neuronal NOS protein content on Western blotting.
High Glucose Activates Nuclear Factor of Activated T Cells in Native Vascular Smooth Muscle
Authors: Nilsson Jenny , Nilsson Lisa M. , Chen Yung-Wu , Molkentin Jeffery D. , Erlinge David , Gomez Maria F.
Published: February 2006

Objective—

Hyperglycemia has been suggested to play a role in the development of vascular disease associated with diabetes. Atypical Ca
2+
signaling and gene expression are characteristic of vascular dysfunction; however, little is known regarding the effects of high glucose on Ca
2+
-dependent transcription in the vascular wall.

Methods and Results—

Using confocal immunofluorescence, we show that modest elevation of extracellular glucose (ie, from 2 to 11.5 mmol/L) increased [Ca
2+
]
i
, leading to nuclear accumulation of nuclear factor of activated T cells (NFAT) in intact cerebral arteries from mouse. This was accompanied by increased NFAT-dependent transcriptional activity. Both the increase in Ca
2+
and NFAT activation were prevented by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. We provide evidence that the potent vasoconstrictors and growth stimulators UTP and UDP mediate glucose-induced NFAT activation via P2Y receptors. NFAT nuclear accumulation was inhibited by the voltage-dependent Ca
2+
channel blockers verapamil and nifedipine, the calcineurin inhibitor cyclosporine A, and the novel NFAT blocker A-285222. High glucose also regulated glycogen synthase kinase 3β and c-Jun N-terminal kinase activity, yielding decreased kinase activity and reduced export of NFAT from the nucleus, providing additional mechanisms underlying the glucose-induced NFAT activation.

Conclusions—

Our results identify the calcineurin/NFAT signaling pathwa
y
as a potential metabolic sensor for the arterial smooth muscle response to high glucose.
PKCδ Is Necessary for Smad3 Expression and Transforming Growth Factor β–Induced Fibronectin Synthesis in Vascular Smooth Muscle Cells
Authors: Ryer Evan J. , Hom R. Patrick , Sakakibara Kenji , Nakayama Keiichi I. , Nakayama Keiko , Faries Peter L. , Liu Bo , Kent K. Craig
Published: February 2006

Objective—

The purpose of these studies is to investigate the mechanism by which transforming growth factor (TGF)β1 regulates the synthesis of the extracellular matrix protein fibronectin (FN).

Methods and Results—

TGFβ1 elicited a time-dependent induction of FN protein and mRNA in A10 rat aortic smooth muscle cells (SMCs). Ectopic expression of Smad3 in A10 cells stimulated both basal and TGFβ1-induced FN expression, whereas expression of Smad7 eliminated the TGFβ response. Because TGFβ activated PKCδ in SMCs, we tested the role of PKCδ in regulation of FN expression. Inhibition of PKCδ activity by rottlerin or dominant-negative adenovirus (AdPKCδ DN) blocked TGFβ1’s induction of FN, whereas overexpression of PKCδ enhanced TGFβ’s effect. Moreover, aortic SMCs isolated from PKCδ
−/−
mice exhibited diminished FN induction in response to TGFβ. Furthermore, we found that Smad3 protein and mRNA were markedly reduced in AdPKCδ DN-treated A10 cells and in PKCδ null cells. Finally, restoring Smad3 in rottlerin-treated A10 and PKCδ null cells rescues the ability of TGFβ to upregulate FN protein and mRNA expression.

Conclusion—

Our data suggest that TGFβ-activated PKCδ is critical to maintain normal expression of Smad3, which in turn is required for the induction of fibronectin. PKCδ represents a promising target for treating the fibroproliferative response after arterial injury.
Pericellular Proteases in Angiogenesis and Vasculogenesis
Authors: van Hinsbergh Victor W.M. , Engelse Marten A. , Quax Paul H.A.
Published: February 2006

Pericellular proteases play an important role in angiogenesis and vasculogenesis. They comprise (membrane-type) matrix metalloproteinases [(MT-)MMPs], serine proteases, cysteine cathepsins, and membrane-bound aminopeptidases. Specific inhibitors regulate them. Major roles in initiating angiogenesis have been attributed to MT1-matrix metalloproteinase (MMP), MMP-2, and MMP-9. Whereas MT-MMPs are membrane-bound by nature, MMP-2 and MMP-9 can localize to the membrane by binding to αvβ3-integrin and CD44, respectively. Proteases switch on neovascularization by activation, liberation, and modification of angiogenic growth factors and degradation of the endothelial and interstitial matrix. They also modify the properties of angiogenic growth factors and cytokines. Neovascularization requires cell migration, which depends on the assembly of protease–protein complexes at the migrating cell front. MT1-MMP and urokinase (u-PA) form multiprotein complexes in the lamellipodia and focal adhesions of migrating cells, facilitating proteolysis and sufficient support for endothelial cell migration and survival. Excessive proteolysis causes loss of endothelial cell-matrix interaction and impairs angiogenesis. MMP-9 and cathepsin L stimulate the recruitment and action of blood- or bone-marrow-derived accessory cells that enhance angiogenesis. Proteases also generate fragments of extracellular matrix and hemostasis factors that have anti-angiogenic properties. Understanding the complexity of protease activities in angiogenesis contributes to recognizing new targets for stimulation or inhibition of neovascularization in disease.
Cardiac and Vascular Hypertrophy in Fabry Disease
Authors: Barbey Frédéric , Brakch Noureddine , Linhart Aleš , Rosenblatt-Velin Nathalie , Jeanrenaud Xavier , Qanadli Salah , Steinmann Beat , Burnier Michel , Palecek Tomas , Bultas Jan , Hayoz Daniel
Published: February 2006

Objectives—

Fabry disease is an X-linked disorder resulting from α-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes.

Methods and Results—

Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r
2
=0.27;
P
<0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r
2
=0.39;
P
<0.0004) and LV mass index (r
2
=0.19;
P
=0.028), respectively.

Conclusions—

LVH and CCA IMT occur concomitantly in Fabry suggesting common pathogenesis. The underlying cause may be a circulating growth-promoting factor whose presence has been confirmed in vitro.
Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells
Authors: Bian Weining , Tung Leslie
Published: February 2006

This study examines how a zigzag pattern of conduction, a form of structural heterogeneity frequently found in old or diseased hearts, affects the vulnerability to reentry during rapid pacing. A central rectangular island (8×4 mm) containing a predefined zigzag pattern was created in cultured isotropic monolayers of neonatal rat ventricular myocytes. Impulse propagation was optically mapped from 253 sites using voltage-sensitive dye and was anisotropic within the zigzag island. With increasing interval between neighboring transverse connections (
a
), relative to the distance between longitudinal strands (
b
), transverse conduction velocity (CV) decreased to 66±6%, 20±2%, and 15±2% of CV in the surrounding isotropic region, whereas longitudinal CV increased to 102±8%, 113±12%, and 131±23% for
a
:
b
ratios of 1:1, 1:5, and 1:9, respectively. During rapid pacing, propagation distal to the island was steered from the side of the island with more transverse connections (“dominant” side) toward the side with fewer connections (“weak” side). Increased asymmetry in the pattern accentuated this effect, and resulted in increased rate-dependent differences in CV on the 2 sides. Consequently, a functional obstacle formed on the weak side, followed by development of single loop reentry. The reentrant wave revolved around a line of block defined by the border of the island. Reentry chirality was determined by the weak side location, and the pacing rate needed to initiate reentry decreased with increased asymmetry in the pattern. In conclusion, reentry is readily induced by rapid pacing in confluent cardiac cell monolayers containing a central and asymmetric island of zigzag conduction.
Chronic
Chlamydia pneumoniae
Infection and Stroke in Cameroon
Authors: Njamnshi Alfred K. , Blackett Kathleen Ngu , Mbuagbaw Josephine N. , Gumedze Freedom , Gupta Sandeep , Wiysonge Charles S.
Published: February 2006

Background and Purpose—

To determine the relationship between chronic
Chlamydia pneumoniae
infection and stroke in Cameroon.

Methods—

Sixty-four consecutive stroke patients 26 to 80 years of age were enrolled at 2 tertiary hospitals in Yaoundé, Cameroon, between March 2000 and December 2001 and matched for age and sex to 64 controls. We measured IgG (1/64) and IgA (1/16) titers against
C pneumoniae
in both patients and controls using a validated microimmunofluorescence technique.

Results—

There was no significant difference between cases and controls with respect to hypertension (
P
=0.2), smoking (
P
=0.53), alcohol intake (
P
=0.8), body mass index (
P
=0.49), waist-to-hip ratio (
P
=0.14), and diabetes (
P
=0.76). IgA antibodies were detected in 50 (78.1%) patients and 27 (42.2%) controls (odds ratio [OR] 4.29; 95% CI, 1.84 to 11.56;
P
=0.0002), and IgG antibodies in 41 (64.1%) patients and 35 (54.7%) controls (OR, 1.46; 95% CI, 0.68 to 3.22;
P
=0.29). For confirmed thrombotic stroke, the association with IgA antibodies became stronger (OR, 21.0; 95% CI, 3.38 to 868.45;
P
<0.0001), but there was still no association with IgG antibodies (OR, 1.86; 95% CI, 0.69 to 5.50;
P
=0.18).

Conclusions—

Our study shows a strong statistical association between (IgA, and not IgG, as a serological marker of) chronic
C pneumoniae
infection and stroke for the first time in a resident indigenous African population. These findings, if confirmed, may have important policy implications (in terms of antibiotic use in stroke prevention) in sub-Saharan Africa.