bluuebunny/crossref_metadata_2025 huggingface dataset:
FUZZY CLUSTERING BASED ON INTUITIONISTIC FUZZY RELATIONS
Authors: HUNG WEN-LIANG , LEE JINN-SHING , FUH CHENG-DER
Published: October 2004

It is well known that an intuitionistic fuzzy relation is a generalization of a fuzzy relation. In fact there are situations where intuitionistic fuzzy relations are more appropriate. This paper discusses the fuzzy clustering based on intuitionistic fuzzy relations. On the basis of max -t & min -s compositions, we discuss an n-step procedure which is an extension of Yang and Shih's [17] n-step procedure. A similarity-relation matrix is obtained by beginning with a proximity-relation matrix using the proposed n-step procedure. Then we propose a clustering algorithm for the similarity-relation matrix. Numerical comparisons of three critical max -t & min -s compositions: max -t1 & min -s1, max -t2 & min -s2 and max -t3 & min -s3, are made. The results show that max -t1 & min -s1 compositions has better performance. Sometimes, data may be missed with an incomplete proximity-relation matrix. Imputation is a general and flexible method for handling missing-data problem. In this paper we also discuss a simple form of imputation is to estimate missing values by max -t & min -s compositions.
1/f NOISE IN LARGE SIGNAL OPERATION OF PASSIVE COMPONENTS
Authors: MARTINI GIUSEPPE
Published: October 2004

A model for the 1/f noise in large signal operation of linear passive one-port (e.g. carbon or polysilicon resistors) is given. Starting from the Hooge's formula, that holds when the component is operated under DC bias, it is shown that the noise current is simply proportional to the product between the conductivity fluctuation and the time-dependent large signal applied to the component. Otherwise stated, the 1/f noise exhibited by passive components in large signal operation arises from the intermodulation between the stochastic process "conductivity fluctuation" and the signal applied to the component. Detailed calculations of both autocorrelation function and power spectrum of the resulting noise current are given; different time dependence of the signal applied to the component are considered. Of particular relevance in practical applications is the case of sinusoidal signal plus an eventual DC bias; in this case the resulting noise current is a cyclostationary stochastic process, and its behaviour can be conveniently described by the cyclic autocorrelation functions or by the cyclic power spectra. The measured power spectra of the noise current of carbon resistors with DC bias and large periodic signal applied to them, are in good agreement with those calculated from the proposed model. The agreement of the measured power spectra with those predicted by the model allows to conclude that the physical origin of 1/f noise in passive components does not depend on the applied bias, DC or large signal alternating, since, in any case, the noise current is conveniently modeled by intermodulation (product) between the "conductivity fluctuation" stochastic process and the applied signal.
STOCHASTIC PHASE-FIELD SIMULATIONS OF SYMMETRIC ALLOY SOLIDIFICATION
Authors: BENÍTEZ R. , RAMÍREZ-PISCINA L.
Published: October 2004

We study initial transient stages in directional solidification by means of a non-variational phase field model with fluctuations. This model applies for the symmetric solidification of dilute binary solutions and does not invoke fluctuation-dissipation theorem to account for the fluctuation statistics. We devote our attention to the transient regime during which concentration gradients are building up and fluctuations act to destabilize the interface. To this end, we calculate both the temporally dependent growth rate of each mode and the power spectrum of the interface evolving under the effect of fluctuations. Quantitative agreement is found when comparing the phase-field simulations with theoretical predictions.
THE USE OF ELECTROCHEMICAL NOISE ANALYSIS ON CORRODING SYSTEMS
Authors: MONTESPERELLI G. , GUSMANO G.
Published: October 2004

This paper gives an overview of the use of Electrochemical Noise (EN) for corrosion studying and monitoring. Since the quality and reliability of noise data are affected by a number of acquisition parameters, such as sampling interval, sampling duration, D.C. trend and instrumental noise, some experimental and practical aspects were discussed. The use of statistical parameters such as standard deviation, Pit Index and/or Localization Index and Noise Resistance to analyze noise data of corroding systems were examined. Many experimental applications of Electrochemical Noise Measurements on different metals and alloys were given. EN data have been compared with traditional electrochemical techniques. EN allowed to characterize the corrosion behavior of samples giving in some cases good quantitative estimation.

The transposition of current and potential noise acquisition in the frequency domain (by Fast Fourier Transform and/or Maximum Entropy Method), gave further information on corrosion mechanism and in particular permitted to identify the type of corrosion. Finally the use of Discriminant Analysis permitted to deduce the best sampling frequency and sampling duration for EN acquisition, able to discriminate between two different situations.
GRAZING SYSTEMS, ECOSYSTEM RESPONSES, AND GLOBAL CHANGE
Authors: Asner Gregory P. , Elmore Andrew J. , Olander Lydia P. , Martin Roberta E. , Harris A. Thomas
Published: October 2004

▪ Abstract  Managed grazing covers more than 25% of the global land surface and has a larger geographic extent than any other form of land use. Grazing systems persist under marginal bioclimatic and edaphic conditions of different biomes, leading to the emergence of three regional syndromes inherent to global grazing: desertification, woody encroachment, and deforestation. These syndromes have widespread but differential effects on the structure, biogeochemistry, hydrology, and biosphere-atmosphere exchange of grazed ecosystems. In combination, these three syndromes represent a major component of global environmental change.
CONSTRUCTION MATERIALS AND THE ENVIRONMENT
Authors: Horvath Arpad
Published: October 2004

▪ Abstract  No other industry in the United States uses more materials by weight than the construction industry. Because of its economic strength and societal importance, it is also a significant polluter and a target of growing stakeholder scrutiny. This review offers an extended, supply chain inclusive framework for the study of the construction industry that serves all the life-cycle stages of society's infrastructure systems, and it summarizes selected literature on the life-cycle environmental assessment of construction materials, designs, and processes. On the basis of identified knowledge gaps, a research agenda is discussed for lesser-studied questions in order to first understand and then eventually reduce the environmental impacts of construction materials, processes, and activities.
ENERGY INFRASTRUCTURE AND SECURITY
Authors: Farrell Alexander E. , Zerriffi Hisham , Dowlatabadi Hadi
Published: October 2004

▪ Abstract  Concerns about safeguarding key infrastructures (such as energy, communications, banking, and roads) from deliberate attack are long-standing, but since the end to the cold war, emphasis has turned to the possible impacts of terrorism. Activities to address these concerns are sometimes called critical infrastructure protection (CIP), a concept that is somewhat different from the one of “energy security,” which focuses on politically and economically motivated supply interruptions. Different elements of the energy infrastructure are characterized by distinct vulnerabilities. Breaches of security in nuclear plants can lead to large-scale environmental disasters—but the infrastructure is concentrated and relatively easy to guard. Oil and gas production, transportation, and refining infrastructures are often spatially concentrated, and disruptions can lead to shortages if supply is not restored before stockpiles are exhausted. Traditional electricity infrastructures suffer from the need for system-wide integrity to ensure supply reliability, having critical facilities spatially concentrated (substations), and insignificant storage capacity for emergency supply. This review discusses how energy infrastructure and security are related, how this relationship differs from traditional energy security concepts, and what it may mean for private and policy decisions. Key concepts include redundancy, diversity, resilience, storage, decentralization, and interdependence. The concept of CIP is still relatively new and is likely to evolve over time, possibly away from a “guards, gates, and guns” defensive approach and toward a design approach that yields systems that are inherently harder to successfully attack. Such survivable systems may feature distributed intelligence, control, and operations.
MARINE RESERVES AND OCEAN NEIGHBORHOODS: The Spatial Scale of Marine Populations and Their Management
Authors: Palumbi Stephen R.
Published: October 2004

▪ Abstract  The movement of individuals defines a spatial neighborhood that can help determine marine management strategies. Here, I briefly review four fields of marine biology that each differentially illuminate the scale of marine neighborhoods: effects of marine reserves, tagging studies, microchemistry, and population genetics. These suggest adult neighborhood sizes for many demersal fish and invertebrates as small as kilometers and up to 10 to 100 km. Larval dispersal may be shorter than previously suspected: neighborhood sizes of 10 to 100 km for invertebrates and 50 to 200 km for fish are common in current compilations.

How can small reserves protect such species? One conceptual framework is to set reserve size based on adult neighborhood sizes of highly fished species and determine spacing of a reserve network based on larval neighborhoods. The multispecies nature of fisheries demands that network designs accommodate different life histories and take into account the way local human communities use marine resources.
CURRENT UNCERTAINTIES IN ASSESSING AEROSOL EFFECTS ON CLIMATE
Authors: Menon Surabi
Published: October 2004

▪ Abstract  The effect of anthropogenic emissions from activities, such as fossil-fuel, biomass, and biofuel burning; transportation; and land-clearing; have a profound impact on the climate system. The impact of these activities is manifested in observed changes in temperature, precipitation, sea-level rise, melting of glaciers, air quality, health, and agriculture yields, to name a few. The obvious question to ask is the role that these different processes play in affecting climate and what action could one impose to curtail or constrain adverse human impacts on climate. Greenhouse gases have long been studied, as they play a major role in changing climate. But over the past 10–20 years, aerosols have emerged as the other big contenders in climate change studies. This review focuses on the current understanding of the effects of aerosols on climate, with an emphasis on the thermodynamical and indirect aerosol effects. We also examine available measurements that could be used to decipher the aerosol influence on climate, with an outlook on how the uncertainties in aerosol effects may impact future climate predictions and policy changes.
PROSPECTS FOR CARBON CAPTURE AND STORAGE TECHNOLOGIES
Authors: Anderson Soren , Newell Richard
Published: October 2004

▪ Abstract  Carbon capture and storage (CCS) technologies remove carbon dioxide from flue gases for storage in geologic formations or the ocean. We find that CCS is technically feasible, with current costs of about $200 to $250 per ton of carbon. Although currently a relatively expensive mitigation option, CCS could be attractive if we have a stringent carbon policy, if CCS turns out unexpectedly inexpensive relative to other options, or if it is otherwise desired to retain fossil fuels as part of the energy mix while reducing carbon emissions. Near-term prospects favor CCS for electric power plants and certain industrial sources with storage in depleted oil and gas reservoirs as opposed to aquifers. Deep aquifers may provide an attractive longer-term-storage option, whereas ocean storage poses greater technical and environmental uncertainty. CCS should be seriously considered for addressing climate change, alongside energy efficiency and carbon-free energy, although significant environmental, technical, and political uncertainties and obstacles remain.
α1-Adrenoceptors stimulate a Gαs protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart
Authors: Gallego Mónica , Setién Raúl , Puebla Lilian , Boyano-Adánez María del Carmen , Arilla Eduardo , Casis Oscar
Published: October 2004

α1-Adrenoceptor stimulation prolongs the duration of the cardiac action potentials and leads to positive inotropic effects by inhibiting the transient outward K+ current ( Ito). In the present study, we have examined the role of several protein kinases and the G protein involved in Ito inhibition in response to α1-adrenoceptor stimulation in isolated adult rat ventricular myocytes. Our findings exclude the classic α1-adrenergic pathway: activation of the G protein Gαq, phospholipase C (PLC), and protein kinase C (PKC), because neither PLC, nor PKC, nor Gαq blockade prevents the α1-induced Ito reduction. To the contrary, the α1-adrenoceptor does not inhibit Ito in the presence of protein kinase A (PKA), adenylyl cyclase, or Gαs inhibitors. In addition, PKA and adenylyl cyclase activation inhibit Ito to the same extent as phenylephrine. Finally, we have shown a functional coupling between the α1-adrenoceptor and Gαs in a physiological system. Moreover, this coupling seems to be compartmentalized, because the α1-adrenoceptor increases cAMP levels only in intact cells, but not in isolated membranes, and the effect on Ito disappears when the cytoskeleton is disrupted. We conclude that α1-adrenoceptor stimulation reduces the amplitude of the Ito by activating a Gαs protein and the cAMP/PKA signaling cascade, which in turn leads to Ito channel phosphorylation.
Calmodulin interactions with IQ peptides from voltage-dependent calcium channels
Authors: Black D. J. , Halling D. Brent , Mandich David V. , Pedersen Steen E. , Altschuld Ruth A. , Hamilton Susan L.
Published: October 2004

Calmodulin (CaM) functions as a Ca2+ sensor for inactivation and, in some cases, facilitation of a variety of voltage-dependent Ca2+ channels. A crucial determinant for CaM binding to these channels is the IQ motif in the COOH-terminal tail of the channel-forming subunit. The binding of CaM to IQ peptides from Lc-, P/Q-, and R-type, but not N-type, voltage-dependent Ca2+ channels increases the Ca2+ affinity of both lobes of CaM, producing similar N- and C-lobe Ca2+ affinities. Ca2+ associates with and dissociates from the N-lobe much more rapidly than the C-lobe when CaM is bound to the IQ peptides. Compared with the other IQ peptides, CaM-bound Lc-IQ has the highest Ca2+ affinity and the most rapid rates of Ca2+ association at both lobes, which is likely to make Ca2+ binding to CaM, bound to this channel, less sensitive than other channels to intracellular Ca2+ buffers. These kinetic differences in Ca2+ binding to the lobes of CaM when bound to the different IQ motifs may explain both the ability of CaM to perform multiple functions in these channels and the differences in CaM regulation of the different voltage-dependent Ca2+ channels.
Three-dimensional simulation of calcium waves and contraction in cardiomyocytes using the finite element method
Authors: Okada Jun-ichi , Sugiura Seiryo , Nishimura Satoshi , Hisada Toshiaki
Published: October 2004

To investigate the characteristics and underlying mechanisms of Ca2+ wave propagation, we developed a three-dimensional (3-D) simulator of cardiac myocytes, in which the sarcolemma, myofibril, and Z-line structure with Ca2+ release sites were modeled as separate structures using the finite element method. Similarly to previous studies, we assumed that Ca2+ diffusion from one release site to another and Ca2+-induced Ca2+ release were the basic mechanisms, but use of the finite element method enabled us to simulate not only the wave propagation in 3-D space but also the active shortening of the myocytes. Therefore, in addition to the dependence of the Ca2+ wave propagation velocity on the sarcoplasmic reticulum Ca2+ content and affinity of troponin C for Ca2+, we were able to evaluate the influence of active shortening on the propagation velocity. Furthermore, if the initial Ca2+ release took place in the proximity of the nucleus, spiral Ca2+ waves evolved and spread in a complex manner, suggesting that this phenomenon has the potential for arrhythmogenicity. The present 3-D simulator, with its ability to study the interaction between Ca2+ waves and contraction, will serve as a useful tool for studying the mechanism of this complex phenomenon.
Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury
Authors: Date Taro , Mochizuki Seibu , Belanger Adam J. , Yamakawa Midori , Luo Zhengyu , Vincent Karen A. , Cheng Seng H. , Gregory Richard J. , Jiang Canwen
Published: October 2004

Preconditioning in cultured cardiomyocytes elevates the expression of several protective genes including Glut-4 and heat shock protein (HSP)70. Hypoxia-inducible factor-1 (HIF-1) is known to mediate the transcriptional activation of hypoxia-responsive genes. In this study, we examined the effect of adenovirus-mediated expression of constitutively stable hybrid forms of HIF-1α on cardiomyocyte viability and gene expression. Cultured neonatal rat cardiomyocytes were subjected to simulated ischemia-reperfusion with or without preinfection with recombinant adenoviral vectors [Ad2/HIF-1α/herpes simplex virus protein VP16 and Ad2/HIF-1α/nuclear factor-κB (NF-κB)]. Cellular viability and mRNA levels of several cardioprotective genes were measured. We demonstrated that infection with Ad2/HIF-1α/VP16 and Ad2/HIF-1α/NF-κB mimicked the upregulation of the mRNA levels of vascular endothelial growth factor (VEGF), Glut-1, Glut-4, HSP70, and inducible NO synthase (iNOS) and the protection of cultured neonatal rat cardiomyocytes by late-phase preconditioning against simulated ischemia-reperfusion. The same dose of a control viral vector expressing no transgene had no effect. Preconditioning also elevated HIF-1α protein levels. These results suggest that adenovirus-mediated expression of HIF-1α/VP16 or HIF-1α/NF-κB, a constitutively stable hybrid transcriptional factor, protected cultured neonatal cardiomyocytes against simulated ischemia-reperfusion injury by inducing multiple protective genes.
Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo
Authors: Langevin Helene M. , Bouffard Nicole A. , Badger Gary J. , Iatridis James C. , Howe Alan K.
Published: October 2004

Cytoskeleton-dependent changes in cell shape are well-established factors regulating a wide range of cellular functions including signal transduction, gene expression, and matrix adhesion. Although the importance of mechanical forces on cell shape and function is well established in cultured cells, very little is known about these effects in whole tissues or in vivo. In this study we used ex vivo and in vivo models to investigate the effect of tissue stretch on mouse subcutaneous tissue fibroblast morphology. Tissue stretch ex vivo (average 25% tissue elongation from 10 min to 2 h) caused a significant time-dependent increase in fibroblast cell body perimeter and cross-sectional area (ANOVA, P < 0.01). At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in stretched than in unstretched tissue. Fibroblasts in stretched tissue had larger, “sheetlike” cell bodies with shorter processes. In contrast, fibroblasts in unstretched tissue had a “dendritic” morphology with smaller, more globular cell bodies and longer processes. Tissue stretch in vivo for 30 min had effects that paralleled those ex vivo. Stretch-induced cell body expansion ex vivo was inhibited by colchicine and cytochalasin D. The dynamic, cytoskeleton-dependent responses of fibroblasts to changes in tissue length demonstrated in this study have important implications for our understanding of normal movement and posture, as well as therapies using mechanical stimulation of connective tissue including physical therapy, massage, and acupuncture.
Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress
Authors: Lamitina S. Todd , Strange Kevin
Published: October 2004

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age- 1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age- 1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age- 1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf- 2/ age- 1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.
Pronounced HR variability after exercise in inferior ischemia: evidence that the cardioinhibitory vagal reflex is invoked by exercise-induced inferior ischemia
Authors: Tahara Nobuhiro , Takaki Hiroshi , Taguchi Atsushi , Suyama Kazuhiro , Kurita Takashi , Shimizu Wataru , Miyazaki Shunichi , Kawada Toru , Sunagawa Kenji
Published: October 2004

Potent cardioinhibitory vagal reflex resulting in bradycardia and hypotension has been observed under particular conditions of transmural inferior ischemia and its reperfusion, such as those observed with acute infarction. However, whether exercise-induced ischemia with ST depressions that is subendocardial and that might be recurrently experienced in daily activities can evoke this reflex remains unknown. In patients with exercise-induced ST depressions due to either inferior [right coronary artery stenosis (RCA), n = 52] or anterior ischemia [left anterior descending artery stenosis (LAD), n = 51], we evaluated post exercise vagal activity (from 0 to 6 min) by the time constant of heart rate (HR) decay and HR variability by 30-s averages of the absolute values of successive RR interval differences (ΔRR). Exercise parameters were similar between groups. The time constant was slightly but significantly shorter in RCA than LAD patients (79 ± 24 vs. 93 ± 29 s, P < 0.01). More significantly, ΔRR early after exercise (0.5–2.5 min) was approximately twofold greater in RCA than LAD patients (from +76 to +118%, P < 0.001), indicating pronounced vagal activity stimulated by inferior ischemia. Revascularization prolonged the time constant ( P < 0.05) and attenuated recovery ΔRR in RCA patients ( P < 0.05, n = 10) but did not change both parameters in LAD patients ( n = 12). As well as acute inferior infarction, exercise-induced inferior subendocardial ischemia, which might recurrently occur in daily activities, activates the cardioinhibitory reflex. These new findings must be taken into account in interpreting vagal activity in patients with coronary artery disease.
Dynamic cerebral autoregulation during exhaustive exercise in humans
Authors: Ogoh Shigehiko , Dalsgaard Mads K. , Yoshiga Chie C. , Dawson Ellen A. , Keller David M. , Raven Peter B. , Secher Niels H.
Published: October 2004

We investigated whether dynamic cerebral autoregulation is affected by exhaustive exercise using transfer-function gain and phase shift between oscillations in mean arterial pressure (MAP) and middle cerebral artery (MCA) mean blood flow velocity ( Vmean). Seven subjects were instrumented with a brachial artery catheter for measurement of MAP and determination of arterial Pco2 (PaCO2) while jugular venous oxygen saturation (SvO2) was determined to assess changes in whole brain blood flow. After a 10-min resting period, the subjects performed dynamic leg-cycle ergometry at 168 ± 5 W (mean ± SE) that was continued to exhaustion with a group average time of 26.8 ± 5.8 min. Despite no significant change in MAP during exercise, MCA Vmean decreased from 70.2 ± 3.6 to 57.4 ± 5.4 cm/s, SvO2 decreased from 68 ± 1 to 58 ± 2% at exhaustion, and both correlated to PaCO2 (5.5 ± 0.2 to 3.9 ± 0.2 kPa; r = 0.47; P = 0.04 and r = 0.74; P < 0.001, respectively). An effect on brain metabolism was indicated by a decrease in the cerebral metabolic ratio of O2 to [glucose + one-half lactate] from 5.6 to 3.8 ( P < 0.05). At the same time, the normalized low-frequency gain between MAP and MCA Vmean was increased ( P < 0.05), whereas the phase shift tended to decrease. These findings suggest that dynamic cerebral autoregulation was impaired by exhaustive exercise despite a hyperventilation-induced reduction in PaCO2.
Syntaxin-1A Binds to and Modulates the Slo Calcium-Activated Potassium Channel via an Interaction That Excludes Syntaxin Binding to Calcium Channels
Authors: Cibulsky Susan M. , Fei Hong , Levitan Irwin B.
Published: October 2004

From its position in presynaptic nerve terminals, the large conductance Ca2+-activated K+ channel, Slo, regulates neurotransmitter release. Several other ion channels known to control neurotransmitter release have been implicated in physical interactions with the neurotransmitter release machinery. For example, the Cav2.2 (N-type) Ca2+ channel binds to and is modulated by syntaxin-1A and SNAP-25. Furthermore, a close juxtaposition of Slo and Cav2.2 is presumed to be necessary for functional coupling between the two channels, which has been shown in neurons. We report that Slo exhibits a strong association with syntaxin-1A. Robust co-immunoprecipitation of Slo and syntaxin-1A occurs from transfected HEK293 cells as well as from brain. However, despite this strong interaction and the known association between syntaxin-1A and the II–III loop of Cav2.2, these three proteins do not co-immunoprecipitate in a trimeric complex from transfected HEK293 cells. The Slo-syntaxin-1A co-immunoprecipitation is not significantly influenced by [Ca2+]. Multiple relatively weak interactions may sum up to a tight physical coupling of full-length Slo with syntaxin-1A: the C-terminal tail and the S0–S1 loop of Slo each co-immunoprecipitate with syntaxin-1A. The presence of syntaxin-1A leads to reduced Slo channel activity due to an increased V1/2 for activation in 100 nM, 1 μM, and 10 μM Ca2+, reduced voltage-sensitivity in 1 μM Ca2+, and slower rates of activation in 10 μM Ca2+. Potential physiological consequences of the interaction between Slo and syntaxin-1A include enhanced excitability through modulation of Slo channel activity and reduced neurotransmitter release due to disruption of syntaxin-1A binding to the Cav2.2 II–III loop.
Spatiotemporal Characteristics of Neuronal Sensory Integration in the Barrel Cortex of the Rat
Authors: Ego-Stengel Valérie , Mello E Souza Tadeu , Jacob Vincent , Shulz Daniel E.
Published: October 2004

In primary sensory cortices, neuronal responses to a stimulus presented as part of a rapid sequence often differ from responses to an isolated stimulus. It has been reported that sequential stimulation of two whiskers produces facilitatory modulations of barrel cortex neuronal responses. These results are at odds with the well-known suppressive interaction that has been usually described. Herein, we have examined the dependency of response modulation on the spatiotemporal pattern of stimulation by varying the spatial arrangement of the deflected vibrissae, the temporal frequency of stimulation, and the time interval between whisker deflections. Extracellular recordings were made from primary somatosensory cortex of anesthetized rats. Two contralateral whiskers were stimulated at 0.5 and 8 Hz at intervals ranging from 0 to ±30 ms. Response interactions were assessed during stimulation of the principal and adjacent whiskers, first from the same row and second from the same arc. When tested at 0.5 Hz, 59% of single units showed a statistically significant suppressive interaction, whereas response facilitation was found in only 6% of cells. In contrast, at 8 Hz, a significant supralinear summation was observed in 19% of the cells, particularly for stimulations along an arc rather than along a row. Multi-unit recordings showed similar results. These observations indicate that most of the interactions in the barrel cortex during two-whisker stimulation are suppressive. However, facilitation can be revealed when stimuli are applied at a physiological frequency and could be the basis for internal representations of the spatiotemporal pattern of the stimulus.
The field of moduli of quaternionic multiplication on abelian varieties
Authors: Rotger Victor
Published: October 2004

We consider principally polarized abelian varieties with quaternionic multiplication over number fields and we study the field of moduli of their endomorphisms in relation to the set of rational points on suitable Shimura varieties.
Finite‐part singular integral approximations in Hilbert spaces
Authors: Ladopoulos E. G. , Tsamasphyros G. , Zisis V. A.
Published: October 2004

Some new approximation methods are proposed for the numerical evaluation of the finite‐part singular integral equations defined on Hilbert spaces when their singularity consists of a homeomorphism of the integration interval, which is a unit circle, on itself. Therefore, some existence theorems are proved for the solutions of the finite‐part singular integral equations, approximated by several systems of linear algebraic equations. The method is further extended for the proof of the existence of solutions for systems of finite‐part singular integral equations defined on Hilbert spaces, when their singularity consists of a system of diffeomorphisms of the integration interval, which is a unit circle, on itself.
Clifford algebra‐valued orthogonal polynomials in the open unit ball of Euclidean space
Authors: Brackx Fred , De Schepper Nele , Sommen Frank
Published: October 2004

A new method for constructing Clifford algebra‐valued orthogonal polynomials in the open unit ball of Euclidean space is presented. In earlier research, we only dealt with scalar‐valued weight functions. Now the class of weight functions involved is enlarged to encompass Clifford algebra‐valued functions. The method consists in transforming the orthogonality relation on the open unit ball into an orthogonality relation on the real axis by means of the so‐called Clifford‐Heaviside functions. Consequently, appropriate orthogonal polynomials on the real axis give rise to Clifford algebra‐valued orthogonal polynomials in the unit ball. Three specific examples of such orthogonal polynomials in the unit ball are discussed, namely, the generalized Clifford‐Jacobi polynomials, the generalized Clifford‐Gegenbauer polynomials, and the shifted Clifford‐Jacobi polynomials.
Monocyte chemoattractant protein-1–induced angiogenesis is mediated by vascular endothelial growth factor-A
Authors: Hong Kyung Hee , Ryu Jewon , Han Ki Hoon
Published: October 2004

Monocyte chemoattractant protein-1 (MCP-1) has been recognized as an angiogenic chemokine. In the present study, we investigated the detailed mechanism by which MCP-1 induces angiogenesis. We found that MCP-1 up-regulated hypoxia-inducible factor 1α (HIF-1α) gene expression in human aortic endothelial cells (HAECs), which induced vascular endothelial growth factor-A165 (VEGF-A165) expression in the aortic wall and HAECs through activation of p42/44 mitogen-activated protein kinase (MAPK). In vivo angiogenesis assay using chick chorioallantoic membrane (CAM) showed that MCP-1–induced angiogenesis was as potent as that induced by VEGF-A165 and completely inhibited by a VEGF inhibitor, Flt2-11. The inhibition of RhoA small G protein did not affect MCP-1–induced VEGF-A165 production and secretion but completely blocked both MCP-1– and VEGF-A–induced new vessel formation, as determined by CAM assay. These results suggest that MCP-1–induced angiogenesis is composed largely of 2 sequential steps: the induction of VEGF-A gene expression by MCP-1 and the subsequent VEGF-A–induced angiogenesis.
Caryoscope: An Open Source Java application for viewing microarray data in a genomic context
Authors: Awad Ihab AB , Rees Christian A , Hernandez-Boussard Tina , Ball Catherine A , Sherlock Gavin
Published: October 2004

Background

Microarray-based comparative genome hybridization experiments generate data that can be mapped onto the genome. These data are interpreted more easily when represented graphically in a genomic context.

Results

We have developed Caryoscope, which is an open source Java application for visualizing microarray data from array comparative genome hybridization experiments in a genomic context. Caryoscope can read General Feature Format files (GFF files), as well as comma- and tab-delimited files, that define the genomic positions of the microarray reporters for which data are obtained. The microarray data can be browsed using an interactive, zoomable interface, which helps users identify regions of chromosomal deletion or amplification. The graphical representation of the data can be exported in a number of graphic formats, including publication-quality formats such as PostScript.

Conclusion

Caryoscope is a useful tool that can aid in the visualization, exploration and interpretation of microarray data in a genomic context.
Incidence of "quasi-ditags" in catalogs generated by Serial Analysis of Gene Expression (SAGE)
Authors: Anisimov Sergey V , Sharov Alexei A
Published: October 2004

Background

Serial Analysis of Gene Expression (SAGE) is a functional genomic technique that quantitatively analyzes the cellular transcriptome. The analysis of SAGE libraries relies on the identification of ditags from sequencing files; however, the software used to examine SAGE libraries cannot distinguish between authentic versus false ditags ("quasi-ditags").

Results

We provide examples of quasi-ditags that originate from cloning and sequencing artifacts (i.e. genomic contamination or random combinations of nucleotides) that are included in SAGE libraries. We have employed a mathematical model to predict the frequency of quasi-ditags in random nucleotide sequences, and our data show that clones containing less than or equal to 2 ditags (which include chromosomal cloning artifacts) should be excluded from the analysis of SAGE catalogs.

Conclusions

Cloning and sequencing artifacts contaminating SAGE libraries could be eliminated using simple pre-screening procedure to increase the reliability of the data.
Reconstruction of putative DNA virus from endogenous rice tungro bacilliform virus-like sequences in the rice genome: implications for integration and evolution
Authors: Kunii Motoyuki , Kanda Masanori , Nagano Hironori , Uyeda Ichiro , Kishima Yuji , Sano Yoshio
Published: October 2004

Background

Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with the exception of virus-like sequences, do not allow us to trace their origins nor to follow the process of their integration into the host genome. Recent discoveries of virus-like sequences in plant genomes led us to set the objective of elucidating the origin of the repetitive sequences. Endogenous rice tungro bacilliform virus (RTBV)-like sequences (ERTBVs) have been found throughout the rice genome. Here, we reconstructed putative virus structures from RTBV-like sequences in the rice genome and characterized to understand evolutionary implication, integration manner and involvements of endogenous virus segments in the corresponding disease response.

Results

We have collected ERTBVs from the rice genomes. They contain rearranged structures and no intact ORFs. The identified ERTBV segments were shown to be phylogenetically divided into three clusters. For each phylogenetic cluster, we were able to make a consensus alignment for a circular virus-like structure carrying two complete ORFs. Comparisons of DNA and amino acid sequences suggested the closely relationship between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy number. The species carrying low-copy-number of ERTBV segments have been reported to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV sequences was correlated with their copy number in the genome.

Conclusions

These ERTBV segments are unlikely to have functional potential as a virus. However, these sequences facilitate to establish putative virus that provided information underlying virus integration and evolutionary relationship with existing virus. Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a possible role of endogenous virus segments against its related disease.
Effect of splenectomy on type-1/type-2 cytokine gene expression in a patient with adult idiopathic thrombocytopenic purpura (ITP)
Authors: Panitsas Fotios P , Mouzaki Athanasia
Published: October 2004

Background

In view of clinical observations and laboratory results that support a central role of the spleen in idiopathic thrombocytopenic purpura (ITP) pathophysiology, we studied the effect of splenectomy on type-1 and type-2 cytokine gene expression in an adult ITP case, refractory to conservative treatment.

Case presentation

The patient was subjected to splenectomy 9 months after the diagnosis with complete response, attaining platelet counts over 150 × 106/L within 10 days after the operation. Two consecutive blood samples were obtained from the patient, 3 and 7 months after the splenectomy for the purposes of this study. A control group consisted of 11 healthy adults. Peripheral blood mononuclear cells were prepared from each blood sample and cultured in vitro for 8 h with the addition of the mitogens phorbol myristate acetate and ionomycin. Total cellular RNA extracted from 106 cells was submitted to semiquantitave reverse transcriptase-polymerase chain reaction (RT-PCR) for the amplification of IL-2, IFN-γ, IL-4, IL-5, and IL-10 metagraphs. The PCR products were run on ethidium-stained agarose gels, photographed and quantified by densitometry.

A steep decrease of type-1 cytokine expression (IL-2, IFN-γ) and their calculated sum expressing Th1 activity was observed at 7 months post-splenectomy compared to 3 months post-splenectomy, in parallel with a rise of platelet count from 190 × 106/L to 265 × 106/L. The change of type-2 cytokine expression (IL-4, IL-5, IL-10) was slight and the Th2 activity (IL-4+IL-5) remained largely unchanged. The Th1/Th2 ratio, that reflects the pathogenic disease-specific T-cell immune deviation, was accordingly reduced 7 months post-splenectomy (Th1/Th2 = 1.3) compared to 3 months (Th1/Th2 = 3.5).

Conclusions

The reduction of the Th1/Th2 cytokine ratio that was observed over time after splenectomy was accompanied by full clinical remission. Nevertheless, the persistence of a type-1 polarization, even after several months following spleen removal, is suggestive of a more basic abnormality of the immune function in these patients.
Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA) Gold 4 epitope and designed for radioimmunotherapy (RIT) of colorectal cancers
Authors: Garambois Véronique , Glaussel Fabienne , Foulquier Elodie , Ychou Marc , Pugnière Martine , Luo Robin X , Bezabeh Binyam , Pèlegrin André
Published: October 2004

Background

Human monoclonal antibodies (MAbs) are needed for colon cancer radioimmunotherapy (RIT) to allow for repeated injections. Carcinoembryonic antigen (CEA) being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs.

Methods

XenoMouse®-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice.

Results

Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 108 M-1 and 1.30 ± 0.06 × 108 M-1, respectively, as compared with 0.61 ± 0.05 × 108 M-1 for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10-7 M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10-9 M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g), close to that of 131I-X4 (21.7 ± 7.2%ID/g). At 72 h post-injection, 125I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g) whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 ± 4.8%ID/g). At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of VG-IgM biodistribution was not possible in this mouse model in which IgM displays a very short half-life due to poly-Ig receptor expression in the liver.

Conclusion

Our human anti-CEA IgG2κ is a promising candidate for radioimmunotherapy in intact form, as F(ab')2 fragments, or as a bispecific antibody.
Parents' reported preference scores for childhood atopic dermatitis disease states
Authors: Friedman Joëlle Y , Reed Shelby D , Weinfurt Kevin P , Kahler Kristijan H , Walter Emmanuel B , Schulman Kevin A
Published: October 2004

Background

We sought to elicit preference weights from parents for health states corresponding to children with various levels of severity of atopic dermatitis. We also evaluated the hypothesis that parents with children who had been diagnosed with atopic dermatitis would assign different preferences to the health state scenarios compared with parents who did not have a child with atopic dermatitis.

Methods

Subjects were parents of children aged 3 months to 18 years. The sample was derived from the General Panel, Mommies Sub-Panel, and Chronic Illness Sub-Panel of Harris Interactive. Participants rated health scenarios for atopic dermatitis, asthma, and eyeglasses on a visual analog scale, imagining a child was experiencing the described state.

Results

A total of 3539 parents completed the survey. Twenty-nine percent had a child with a history of atopic dermatitis. Mean preference scores for atopic dermatitis were as follows: mild, 91 (95% confidence interval [CI], 90.7 to 91.5); mild/moderate, 84 (95%CI, 83.5 to 84.4); moderate, 73 (95%CI, 72.5 to 73.6); moderate/severe, 61 (95%CI, 60.6 to 61.8); severe, 49 (95% CI, 48.7 to 50.1); asthma, 58 (95%CI, 57.4 to 58.8); and eyeglasses, 87(95%CI, 86.3 to 87.4).

Conclusions

Parents perceive that atopic dermatitis has a negative effect on quality of life that increases with disease severity. Estimates of parents' preferences can provide physicians with insight into the value that parents place on their children's treatment and can be used to evaluate new medical therapies for atopic dermatitis.
The ProActivetrial protocol – a randomised controlled trial of the efficacy of a family-based, domiciliary intervention programme to increase physical activity among individuals at high risk of diabetes [ISRCTN61323766]
Authors: Williams Kate , Prevost A Toby , Griffin Simon , Hardeman Wendy , Hollingworth William , Spiegelhalter David , Sutton Stephen , Ekelund Ulf , Wareham Nicholas , Kinmonth Ann Louise
Published: October 2004

Background

Increasing prevalence of obesity and disorders associated with sedentary living constitute a major global public health problem. While previous evaluations of interventions to increase physical activity have involved communities or individuals with established disease, less attention has been given to interventions for individuals at risk of disease.

Methods/design

ProActiveaims to evaluate the efficacy of a theoretical, evidence- and family-based intervention programme to increase physical activity in a sedentary population, defined as being at-risk through having a parental family history of diabetes. Primary care diabetes or family history registers were used to recruit 365 individuals aged 30–50 years, screened for activity level. Participants were assigned by central randomisation to three intervention programmes: brief written advice (comparison group), or a psychologically based behavioural change programme, delivered either by telephone (distance group) or face-to-face in the family home over one year. The protocol-driven intervention programme is delivered by trained facilitators, and aims to support increases in physical activity through the introduction and facilitation of a range of self-regulatory skills (e.g. goal setting). The primary outcome is daytime energy expenditure and its ratio to resting energy expenditure, measured at baseline and one year using individually calibrated heart rate monitoring. Secondary measures include self-report of individual and family activity, psychological mediators of behaviour change, physiological and biochemical correlates, acceptability, and costs, measured at baseline, six months and one year. The primary intention to treat analysis will compare groups at one-year post randomisation. Estimation of the impact on diabetes incidence will be modelled using data from a parallel ten-year cohort study using similar measures.

Discussion

ProActiveis the first efficacy trial of an intervention programme to promote physical activity in a defined high-risk group accessible through primary care. The intervention programme is based on psychological theory and evidence; it introduces and facilitates the use of self-regulatory skills to support behaviour change and maintenance. The trial addresses a range of methodological weaknesses in the field by careful specification and quality assurance of the intervention programme, precise characterisation of participants, year-long follow-up and objective measurement of physical activity. Due to report in 2005, ProActivewill provide estimates of the extent to which this approach could assist at-risk groups who could benefit from changes in behaviours affecting health, and inform future pragmatic trials.