bluuebunny/crossref_metadata_2025 huggingface dataset:
Discussion: Response of bark tissues to injury and infection
Authors: Biggs A. R. , Merrill W. , Davis D. D.
Published: June 2010

Research of nonspecific defense processes in woody plants has focused on xylem. From these studies the concept of compartmentalization sensu Shigo was developed. Responses of bark to injury and infection, however, are understood poorly. This discussion summarizes evidence for the occurrence of processes similar in function to xylem compartmentalization in bark. We suggest that a developmental approach to research on woody plant responses to injury and infection could result in conceptual unity regarding structural and functional changes in both xylem and bark.
The climatic regions of New Brunswick: a multivariate analysis of meteorological data
Authors: Groenewoud H. van
Published: June 2010

New Brunswick was divided into 11 climatic regions by means of three multivariate statistical analyses (principal component analysis, R and Q type, and cluster analysis) of data on precipitation, various temperature parameters, elevation, latitude, and longitude for 76 climatological stations. These regions form the first-level division for a forest site classification scheme being implemented in New Brunswick. Comparison of the climatic and geological maps of New Brunswick with the plant community distribution shows that either climatic or geologic parameters may control the distribution of the vegetation.
Long-term decomposition and nutrient dynamics in Pacific silver fir needles in western Washington
Authors: Edmonds Robert L.
Published: June 2010

Long-term needle decomposition and nutrient dynamics (N, P, K, Ca, Mg, and Mn) were studied over a 6-year period in a Pacific silver fir (Abiesamabilis (Dougl.) Forb.) ecosystem in western Washington, U.S.A. Weight loss of needles was 41.2% after 14 months and 64.3% after 6 years. Decomposition constants (k values) declined with time of decomposition, but tended to stabilize afer4–6years. The mean residence time of needles was estimated to be 9 years. After 4 years decomposition weight loss paralleled lignin loss. Nitrogen was strongly immobilized in needles with 242% of original mass of N remaining after 4 years and 213% after 6 years. Net mineralization occurred when the C:N ratio fell below 20. Phosphorus appeared to be slightly immobilized in the 9- to 48-month period. Only 49% of the original P mass remained after 6 years. None of the other elements was immobilized during the 6-year period. The element mobility series was N < P < Mn < Ca < Mg < K. Two-year litter bag studies in subalpine coniferous ecosystems are not long enough to study litter decomposition rates and nutrient dynamics.
An evaluation of growth response of young, spaced balsam fir to 3 years of spruce budworm spraying with Bacillusthuringiensis
Authors: Piene H. , MacLean D. A.
Published: June 2010

Growth response of young, spaced balsam fir (Abiesbalsamea (L.) Mill.) to 3 successive years (1979–1981) of treatment with Bacillusthuringiensis Berliner for spruce budworm (Choristoneurafumiferana (Clem.)) control was examined in 20 plots on the Cape Breton Highlands, Nova Scotia. Defoliation commenced in 1976, 3 years before control operations began. Five plots were established both inside and outside the spray block, in areas that had been severely defoliated by budworm and in areas moderately defoliated. All plots in the severely defoliated area suffered heavy tree mortality, but mortality was significantly lower in the protected plots. In contrast, the moderately defoliated plots suffered virtually no tree mortality. The average volume increment of stem-analyzed trees from 1979 to 1981 was 0.63 dm3/tree for protected and 0.43 dm3/tree for unprotected trees in the severely defoliated area versus 4.15 dm3/tree for protected and 3.08 dm3/tree for unprotected trees in the moderately defoliated area. These volume increment values are equivalent to 8.8 m3/ha of growth between 1979 and 1981 for protected plots in the moderately defoliated area, compared with 6.1 m3/ha for unprotected plots. Therefore, a total gain of 2.7 m3/ha can be attributed to the 3 years of B. thuringiensis spraying. Long-term growth responses toB. thuringiensis spraying were not evaluated. Better results would be expected had protection started at the beginning of the budworm outbreak, instead of after 3 years of severe defoliation.
Ten-year growth and nutrition effects of a straw treatment and of repeated fertilization on jack pine
Authors: Weetman G. F. , Fournier R. M.
Published: June 2010

Straw was added over snow to smother ground vegetation (straw experiment) in sample plots in a 45-year-old jack pine (Pinusbanksiana Lamb.) stand in Quebec. Sample plots in the same stand were fertilized six times with N, P, and K in a 10-year period to maintain four foliar N regimes (optimum nutrition experiment). Smothering of ground vegetation with straw improved N nutrition and produced a sustained increase in tree growth. Sustained growth increases were obtained by repeated applications of 56 kg N/ha associated with 1.4% N foliar concentrations in current foliage. Gross volume increments of about 3 m3 • ha−1 • year−1 were sustained with these low applications. Repeated heavy N applications killed trees and reduced growth. Repeated additions of P and K with N did not produce appreciable differences in response from additions of N alone. Increment cores showed the annual development in growth as increasing over most of the 10-year period for low repeated N additions, and as increased and stable over the same period for the straw addition.
Additivity of component biomass regression equations when the underlying model is linear
Authors: Chiyenda Simeon S. , Kozak Antal
Published: June 2010

Results obtained by Kozak (A. Kozak. 1970. For. Chron. 46(5): 402–404.) concerning conditions for additivity of component biomass regression equations are formalized and extended. More specifically Kozak demonstrated, using multiple linear regression equations to model three biomass components (bole, bark, and crown) for individual trees, that corresponding total biomass can be determined as the sum of the component regression equations, provided that the same independent variables are used in each component equation. Clearly, Kozak's result can be extended to the case of k (≥2) component equations and we use this case to give more general conditions for the additivity problem. Results are also given for the estimation and inference problems associated with fitting the total biomass model using the additivity result. Additionally, by using the principle of fitting subject to constraints or what has been termed "conditional fitting," it is demonstrated in this paper that additivity of the component equations can be assured even when different independent variables are used in different component equations subject to certain assumptions being met. This principle is then used to generalize the additivity of component regression equations problem and, finally, an example is given to illustrate the application of this generalized additivity theory.
Observations on the physiological mechanisms and chemical constituents of induced oleoresin synthesis in Pinusresinosa
Authors: Wolter Karl E. , Zinkel Duane F.
Published: June 2010

The stimulation of lightwood formation (oleoresin soaking) in Pinusresinosa Ait. treated with the bipyridylium salt, paraquat (1,1′-dimethyl-4,4′-bipyridylium dichloride), affected various physiological parameters. Respiration, transpiration, and ethylene synthesis were markedly increased and were correlated with the increased production of rosin and turpentine. Photosynthesis, however, was severely inhibited, and phloem transport was not necessary for oleoresin deposition. These marked changes in function reflect a typical wounding response. Ethylene (supplied as Ethrel (2-chloroethylphosphonic acid)) was capable of replacing the stimulatory effect of paraquat, with a 14-fold increase in rosin over controls and a 25-fold increase in turpentine. This increase in turpentine content was accomplished by a significant enhancement in β-pinene content. Ethrel-treated trees also showed an increased abietic acid content, with a concomitant decrease in levopimaric acid.
Growth of rooted cuttings and seedlings in a 40-year-old plantation of eastern white pine
Authors: Struve D. K. , Talbert J. T. , McKeand S. E.
Published: June 2010

To compare long-term performance of rooted cuttings with seedlings in white pine (Pinusstrobus L.), two 37-year-old (40 years from propagation) experimental plantations of rooted cuttings and seedlings were measured for height, diameter at breast height (DBH), and wood specific gravity. In general, rooted cutting origin trees performed as well as or better than seedling origin trees for survival, height, and diameter at breast height. The number of roots per cutting at planting was significantly and positively correlated with DBH at years 9 and 40. Seedling origin trees had significantly higher (P = 0.05) wood specific gravity at one of the two test plantations.
Generality of black spruce biomass estimation equations
Authors: Grigal D. F. , Kernik L. K.
Published: June 2010

We developed a set of equations to estimate biomass of black spruce (Piceamariana (Mill.) B.S.P.), based on data from trees from bogs in Minnesota. The equation for total biomass, based on diameter alone, was similar to most other equations for black spruce in the literature. This relationship appears to have wide generality. Estimates of foliage biomass, arrived at by using the same tree diameter and height but various equations from the literature, differed greatly. These comparisons indicate that stand conditions, such as stocking, are apparently very important in determining mass of black spruce foliage.
A comparison of methods for total sulphur analysis of tree foliage
Authors: Guthrie T. F. , Lowe L. E.
Published: June 2010

Three methods were compared for total sulphur analysis of tree foliage: magnesium nitrate ashing followed by turbidimetry, sodium hypobromite (NaOBr) oxidation followed by colorimetry, and an instrumental method using the Fisher S analyser, model 475. The latter method was found to be substantially better than the other methods with respect to accuracy and speed of analysis, and of satisfactory precision (average coefficient of variation (CV) was 2.5%). Dry ashing resulted in good precision (CV = 1.9%) but only recovered 76% of the reported total S in the United States National Bureau of Standards (NBS) orchard leaf standard. The NaOBr method recovered 88% of reported S from the NBS standard but showed poorer precision (CV = 4.5%). The Fisher analyser had the lowest operating cost per sample, largely owing to lower labour costs.
Weibull diameter distributions for mixed stands of western conifers
Authors: Little Susan N.
Published: June 2010

not available
NUMERICAL COMPUTATIONS OF CONDUCTIVITY IN CONTINUUM PERCOLATION FOR OVERLAPPING SPHEROIDS
Authors: MATSUTANI SHIGEKI , SHIMOSAKO YOSHIYUKI , WANG YUNHONG
Published: June 2010

By numerically solving the generalized Laplace equations by means of the finite difference method, we investigated isotropic electric conductivity of a three-dimensional continuum percolation model consisting of overlapped spheroids of revolution in continuum. Since the computational results strongly depend upon parameters in the discretization methods of the finite difference method, we explored the dependences in details to construct the computational scheme which can represent the continuum percolation model well. Using the discrete scheme, we obtained the conductivity curves, σ =c (p -pc)t, depending upon aspect ratio of the conductive spheroids for the volume fraction p. We found the fact that the critical exponent t is not universal, which depends upon the shape of spheroids with a range varying from 1.58 ± 0.08 to 1.94 ± 0.18 whereas 1.85 is reported as the standard one of cubic lattice case [A. B. Harris, Phys. Rev. B28, 2614 (1983)]. We also discussed its relation to the nonuniversality in the broad distribution continuum percolation models.
SCALING OF INTERNODE DISTANCES IN WEIGHTED COMPLEX NETWORKS
Authors: SIENKIEWICZ JULIAN , HOŁYST JANUSZ A.
Published: June 2010

We extend the previously observed scaling equation connecting the internode distances and nodes' degrees onto the case of weighted networks. We show that the scaling takes a similar form in the empirical data obtained from networks characterized by different relations between node's strength and its degree. In the case of explicit equation for s (k) (e.g. linear or scale-free), the new coefficients of scaling equation can be easily obtained. We support our analysis with numerical simulations for Erdös–Rényi random graphs with different weight distributions.
LATTICE BOLTZMANN SIMULATION OF GASEOUS FINITE-KNUDSEN MICROFLOWS
Authors: TIAN ZHI-WEI , CHEN SHENG , ZHENG CHU-GUANG
Published: June 2010

In this study, microscale gaseous flows in the transitional regime have been investigated by lattice Boltzmann method (LBM). In the existing microflows LBM models, the Knudsen layer correction function has been introduced into the models. According to the kinetic theory rigorously, we choose a proper expression of correction function, and then determine its adjustable parameter. A substitute high-order boundary conditions treatment is adopted to capture the velocity slip, without any difficulties in computing the high-order velocity derivatives. The numerical results of two typical microflows show that: the present results agree with the analytical solutions better than the existing LBM simulations. Evident improvements can also be found, especially for finite Kn microflows.
DIRECTLY ADJUSTING NODE'S IMPACTS TO REALIZE THE SYNCHRONIZATION OF COMPLEX NETWORKS
Authors: ZHANG HAIFENG , ZHAO MING , WANG BINGHONG
Published: June 2010

Most previous studies on the synchronization of complex networks were based on that each node managed to adjust its neighbors coupling strength to enhance synchronizability, i.e. each node tried to adjust its total input coupling strength in a proper way and the neighbor nodes were passively adjusted. From practical and engineering viewpoints, each node should manage to adjust its total output coupling strength to realize synchronization. Moreover, each node's total output coupling strength can be distributed to its neighbors with different proportions. In view of the above reasons, in this paper, we study the synchronization of complex networks under the assumptions that the total output coupling strength of each node is voluntarily/directly distributed to its neighbors with different proportions. What is more, we assume that the total output coupling strength of each node can be nonlinear to its degree. Our analysis and numerical simulations show that the synchronizability can be enhanced dramatically when the parameters are properly selected.
SPONTANEOUS SYMMETRY BREAKING IN A MICROTUBULE-LIKE SYSTEM
Authors: LIU MINGZHE , WANG RUILI , JIANG RUI
Published: June 2010

This paper studies asymmetric exclusion processes on a microtubule-like system with two species of particles. The model is motivated by the structure of microtubules and kinesins and dyneins moving along microtubules in opposite directions. The proposed model is similar to that in J. Phys. A40, 2275 (2007) in which two-channel TASEPs with narrow entrances and parallel update are studied. This paper extended the above-mentioned work to a multiple-channel hollow cylinder case. Thus, each channel has two nearest neighbors in our model. The corresponding rule for narrow entrances is that particles cannot enter the system if either of two nearest-neighbor sites on neighboring channels is occupied by the other species of particles. The phase diagram of the model is obtained from a mean-field approximation and verified by computer simulations. It is shown that the spontaneous symmetry breaking exists with two asymmetric phases: high/low density and low/low density. The flipping process of particles is observed. Bulk density and particle currents are computed. Monte Carlo simulation results deviate from the mean-field prediction when entrance rate α is high, which is due to neglecting correlations among particles in mean-field calculations. The results are also compared with that obtained from two-channel system with one neighbor narrow entrance in parallel update.
FIRST-PRINCIPLES STUDY OF THE EFFECTS OF THE OXYGEN VACANCY ON ELECTRONIC STRUCTURE AND FERROMAGNETISM OF Sn2 Co2O8-δ
Authors: HE KAIHUA , ZHENG GUANG , HONG HANLIE , WAN MIAO , JI GUANGFU
Published: June 2010

The electronic structure and ferromagnetism of Sn 2 Co 2 O 8 and Sn 2 Co 2 O 7 have been investigated based on the first-principles plane-wave pseudopotential method within the generalized gradient approximation. The calculated results reveal that the oxygen vacancy plays an important role in the electronic structure and ferromagnetism. The Sn 2 Co 2 O 8 shows half-metallic behavior, but by introducing single oxygen vacancy, the half-metallic transits to metallic behavior. At the same time, the spin magnetic moment of every Co atom and the total magnetic moment change greatly. For Sn 2 Co 2 O 8 and Sn 2 Co 2 O 7, the total spin magnetic moments are 1.99 and 3.49 uB, respectively.
DETERMINATION OF TRAPPING CENTER PARAMETERS OF Tl2Ga2S3Se LAYERED CRYSTALS BY THERMALLY STIMULATED CURRENT MEASUREMENTS
Authors: YILDIRIM T. , NASSER H. A. , GASANLY N. M.
Published: June 2010

We have carried out thermally stimulated current (TSC) measurements on as-grown Tl 2 Ga 2 S 3 Se layered single crystals in the temperature range 10–60 K with different heating rates of 0.6–1.5 K s1. The data were analyzed by curve fitting, initial rise, and peak shape methods. The results were in good agreement with each other. Experimental evidence was obtained for trapping center in Tl 2 Ga 2 S 3 Se crystal with activation energy of 11 meV. The capture cross section and concentration of the traps were found to be 1.5 × 10-23 cm 2 and 1.44 × 1010 cm -3, respectively. Analysis of the TSC data at different light excitation temperatures leads to a value of 18meV/decade for the traps distribution.
A HYBRID MODEL FOR QUANTUM WELL SOLAR CELLS
Authors: PAULESCU MARIUS , TULCAN-PAULESCU EUGENIA , GRAVILA PAUL
Published: June 2010

Quantum and classical components are blended together in this proposed theoretical model for describing multiple quantum well solar cells (MQWSC) in a p-i-n architecture. The model characteristics are: the use of transfer matrix as a quantum method for finding allowed energies in the coupled quantum wells, the connection of the absorption coefficient in the confined 2D structure to the one in the bulk semiconductor, and the treatment of the whole cell as a pseudo-homogeneous media to determine its reflectance. The resulted model is intended to be a working tool to assess electro-optical properties of MQWSC. Numerical results which relate the performance of the MQWSC to its structure are reported.
COMPLEX NETWORKS: NEW TRENDS FOR THE ANALYSIS OF BRAIN CONNECTIVITY
Authors: CHAVEZ MARIO , VALENCIA MIGUEL , LATORA VITO , MARTINERIE JACQUES
Published: June 2010

Today, the human brain can be studied as a whole. Electroencephalography, magnetoencephalography, or functional magnetic resonance imaging (fMRI) techniques provide functional connectivity patterns between different brain areas, and during different pathological and cognitive neuro-dynamical states. In this tutorial, we review novel complex networks approaches to unveil how brain networks can efficiently manage local processing and global integration for the transfer of information, while being at the same time capable of adapting to satisfy changing neural demands.
NOISE-INDUCED SYNCHRONIZATION IN MULTITROPHIC CHAOTIC ECOLOGICAL SYSTEMS
Authors: HE DAIHAI , STONE LEWI , CAZELLES BERNARD
Published: June 2010

Noise-induced synchronization is an unexpected phenomenon which we show here to have biological relevance for multitrophic ecological systems. We focus on two uncoupled Hastings–Powell systems having oscillatory dynamics. Despite the fact the systems are uncoupled, it is shown that they can nevertheless synchronize by applying common Gaussian noise forcing to a suitably chosen variable in both systems. Complete synchronization is studied in the case of identical oscillators, and intermittent synchronization is analyzed when the oscillators are nonidentical. We discuss how this unusual synchronization phenomenon has features akin to Ecology's well-known "Moran effect."
RETURN TIME STATISTICS AND ANTI-PHASE REGULARIZATION IN COUPLED CHAOTIC MAPS MODELING BURSTING OSCILLATIONS
Authors: ALLIO C. , COURBAGE M.
Published: June 2010

The problem of phase synchronization of coupled chaotic bursting oscillatory systems is studied using the probability distribution of return time to the quiscent state. It is shown that, in some range of the coupling strength, the continuous type distribution becomes discrete and is supported by few values around a preferred one. This shows that the shape and the amplitudes of the spikes are not important and the main aspect of coupling is the change of distribution of the units' time return difference.
Multiobjective A
*
search with consistent heuristics
Authors: Mandow Lawrence , De La Cruz José. Luis Pérez
Published: June 2010

The article describes and analyzes NAMOA
*
, an algorithm for multiobjective heuristic graph search problems. The algorithm is presented as an extension of A
*
, an admissible scalar shortest path algorithm. Under consistent heuristics A
*
is known to improve its efficiency with more informed heuristics, and to be optimal over the class of admissible algorithms in terms of the set of expanded nodes and the number of node expansions. Equivalent beneficial properties are shown to prevail in the new algorithm.
Mainstreaming augmented reality
Authors: Kroeker Kirk L.
Published: June 2010

Advancements in computer vision, object recognition, and related technologies are leading to new levels of sophistication in augmented-reality applications and presenting new ways for humans to relate to the natural world.
Visions of the future
Authors: Underwood Sarah
Published: June 2010

ACM joined forces with the British Computer Society to deliver its first academic research conference in Europe.
Outsourcing versus shared services
Authors: Sako Mari
Published: June 2010

Choosing between outsourcing and shared services has significant implications for long-term corporate strategy.
Is computer science truly scientific?
Authors: Génova Gonzalo
Published: June 2010

Reflections on the (experimental) scientific method in computer science.
The ideal HPC programming language
Authors: Loh Eugene
Published: June 2010

Maybe it's Fortran. Or maybe it just doesn't matter.
Visualizing system latency
Authors: Gregg Brendan
Published: June 2010

Heat maps are a unique and powerful way to visualize latency data. Explaining the results, however, is an ongoing challenge.
Algorithmic game theory
Authors: Roughgarden Tim
Published: June 2010

A new era of theoretical computer science addresses fundamental problems about auctions, networks, and human behavior.
Q&A: From single core to multicore
Authors: Hoffmann Leah
Published: June 2010

Charles P. Thacker discusses the legendary Alto personal computer, the invention of the Ethernet, and his current research on multicore architectures.
Application service providers
Authors: Yao Yurong , Watson Edward , Kahn Beverly K.
Published: June 2010

Introduction

IT outsourcing has been a viable business strategy since the late 1950s when companies began to invest significant resources in outside computing services. As IT managers increasingly used time sharing, contract programming, and facilities management, the next few decades saw accompanying increases in efficiency in software applications and services, not to mention decreased operations costs. In 1989, when Kodak outsourced its entire IT department to IBM and EDS, the business world had to scramble to get over its initial shock. Seemingly overnight, "software" and "service" had become strange bedfellows. The rules of the game had radically changed.

Since the mid-1990s, the explosion in Internet connectivity, increased bandwidth, and the ubiquitous nature of computing have made the delivery of software applications from remote data centers both technologically feasible and economically attractive. A relatively new form of IS outsourcing, Application Services Provision (ASP), provides applications to multiple entities from its data center across a wide area network. Similar to the telephone services model, clients pay a monthly fee to access online applications from an ASP. Advances in encryption and firewall technology remove a client's security concerns for using remotely hosted services. Active research on ASP outsourcing (also called NetSourcing) has attracted academic scholars and business practitioners alike, but few have investigated the specifics of the market and the decision process to adopt the ASP model.

ASPs today are quite different from what they were five years ago, in large part because this dynamic industry has experienced significant merger and acquisition activity. Forty percent of ASPs active in 2001 were no longer in business in 2004. Traditional software companies also have jumped on the ASP bandwagon, developing new technologies to deliver on-demand services. The scope of hosted applications for ASPs has also shifted significantly as certain applications were scrapped for lack of profitability, for example, overall enterprise system hosting with no specific industrial solutions. However, a Forrester report predicted that as eCommerce continued to grow 30% - 40% in 2005, the demand for licensed software products would decrease while demand for hosted services increases. This prediction seems to be reality, as ASP hosting solutions are increasingly viable and attractive business models.

Thus, to update our knowledge of the rapidly changing ASP market and to help practitioners make better-informed ASP adoption decisions, this article addresses two central questions: What is the structure of the current market? And what factors should clients consider in their ASP adoption decisions?
Why do people tag?
Authors: Nov Oded , Ye Chen
Published: June 2010

Introduction

Tagging, or using keywords to add metadata to shared content, is gaining much popularity in recent years. Tags are used to annotate various types of content, including images, videos, bookmarks, and blogs, through web-based systems such as Flickr, YouTube, del.icio.us, and Technorati, respectively. The popularity of tagging is attributed, at least in part, to the benefits users gain from effective sharing and from organization of very large amounts of information.

As tagging receives increasing attention in both research and business communities, studies have found that users vary substantially in their tag usage, and suggested several factors that motivate user tagging. However, to date no quantitative study has assessed the strength of the effects of each motivation on levels of tag usage. This is surprising, since user participation is critical to the sustainability of content sharing communities, and a collaborative tagging system cannot succeed without higher level of user contribution. In what follows, we address this gap, by studying the strength of relationships between several motivations and users' tagging levels on Flickr, a prominent Web 2.0 photo sharing community.

Currently, there are more than 35 million Flickr users, who have so far uploaded more 3 billion photos. Each Flickr user can upload images and make them viewable by self, by designated friends and family, or by all Flickr users. Flickr users can annotate images with tags - unstructured textual labels; and usually images are tagged only by the user who uploaded them.8 These tags make the images searchable by the uploading user, as well as by others. In addition, each user can designate other users as "contacts," people whose photos the user follows (contacts are often reciprocal).

To understand what underlies tagging, we need to find out what motivates sharing in online environments, and in particular, what motivates tagging. Furthermore, we need to measure the degree to which different motivations affect tagging activity. While some studies has identified individual-level motivations for tagging, other studies have looked solely at the social level, focusing on the social presence as a driver of tagging.
The ω-3 fatty acid eicosapentaenoic acid elicits cAMP generation in colonic epithelial cells via a “store-operated” mechanism
Authors: Roy Jessica , Lefkimmiatis Konstantinos , Moyer Mary Pat , Curci Silvana , Hofer Aldebaran M.
Published: June 2010

Eicosapentaenoic acid (EPA) is an ω-3 polyunsaturated fatty acid abundant in fish oil that exerts a wide spectrum of documented beneficial health effects in humans. Because dietary interventions are relatively inexpensive and are widely assumed to be safe, they have broad public appeal. Their endorsement can potentially have a major impact on human health, but hard mechanistic evidence that specifies how these derivatives work at the cellular level is limited. EPA (50 μM) caused a small elevation of cytoplasmic Ca2+concentration ([Ca2+]) in intact NCM460 human colonic epithelial cells as measured by fura 2 and a profound drop of [Ca2+] within the endoplasmic reticulum (ER) of permeabilized cells as monitored by compartmentalized mag-fura 2. Total internal reflection fluorescence microscopy showed that this loss of ER store [Ca2+] led to translocation of the ER-resident transmembrane Ca2+sensor STIM1. Using sensitive FRET-based sensors for cAMP in single cells, we further found that EPA caused a substantial increase in cellular cAMP concentration, a large fraction of which was dependent on the drop in ER [Ca2+], but independent of cytosolic Ca2+. An additional component of the EPA-induced cAMP signal was sensitive to the phosphodiesterase inhibitor isobutyl methylxanthine. We conclude that EPA slowly releases ER Ca2+stores, resulting in the generation of cAMP. The elevated cAMP is apparently independent of classical G protein-coupled receptor activation and is likely the consequence of a newly described “store-operated” cAMP signaling pathway that is mediated by STIM1.
Acid-induced p16 hypermethylation contributes to development of esophageal adenocarcinoma via activation of NADPH oxidase NOX5-S
Authors: Hong Jie , Resnick Murray , Behar Jose , Wang Li Juan , Wands Jack , DeLellis Ronald A. , Souza Rhonda F. , Spechler Stuart J. , Cao Weibiao
Published: June 2010

Inactivation of tumor suppressor gene p16 may play an important role in the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). Hypermethylation of p16 gene promoter is an important mechanism inactivating p16. However, the mechanisms of p16 hypermethylation in EA are not known. Therefore, we examined whether acid increases methylation of p16 gene promoter and whether NADPH oxidase NOX5-S mediates acid-induced p16 hypermethylation in a Barrett's cell line BAR-T and an EA cell line OE33. We found that NOX5-S was present in BAR-T and OE33 cells. Acid-induced increase in H2O2 production and cell proliferation was significantly reduced by knockdown of NOX5-S. Exogenous H2O2 remarkably increased p16 promoter methylation and cell proliferation. In addition, acid treatment significantly increased p16 promoter methylation and decreased p16 mRNA level. Knockdown of NOX5-S significantly increased p16 mRNA, inhibited acid-induced downregulation of p16 mRNA, and blocked acid-induced increase in p16 methylation and cell proliferation. Conversely, overexpression of NOX5-S significantly decreased p16 mRNA and increased p16 methylation and cell proliferation. In conclusion, NOX5-S is present in BAR-T cells and OE33 cells and mediates acid-induced H2O2 production and cell proliferation. NOX5-S is also involved in acid-induced hypermethylation of p16 gene promoter and downregulation of p16 mRNA. It is possible that acid reflux present in BE patients may activate NOX5-S and increase production of reactive oxygen species, which in turn increase p16 promoter methylation, downregulate p16 expression, and increase cell proliferation, thereby contributing to the progression from BE to EA.
Differential transcriptional characteristics of small and large biliary epithelial cells derived from small and large bile ducts
Authors: Glaser S. , Wang M. , Ueno Y. , Venter J. , Wang K. , Chen H. , Alpini G. , Holterman A.
Published: June 2010

Biliary epithelial cells (BEC) are morphologically and functionally heterogeneous. To investigate the molecular mechanism for their diversities, we test the hypothesis that large and small BEC have disparity in their target gene response to their transcriptional regulator, the biliary cell-enriched hepatocyte nuclear factor HNF6. The expression of the major HNF ( HNF6, OC2, HNF1b, HNF1a, HNF4a, C/EBPb, and Foxa2) and representative biliary transport target genes that are HNF dependent were compared between SV40-transformed BEC derived from large (SV40LG) and small (SV40SM) ducts, before and after treatment with recombinant adenoviral vectors expressing HNF6 (AdHNF6) or control LacZ cDNA (AdLacZ). Large and small BEC were isolated from mouse liver treated with growth hormone, a known transcriptional activator of HNF6, and the effects on selected target genes were examined. Constitutive Foxa2, HNF1a, and HNF4a gene expression were 2.3-, 12.4-, and 2.6-fold, respectively, higher in SV40SM cells. This was associated with 2.7- and 4-fold higher baseline expression of HNF1a- and HNF4a-regulated ntcp and oatp1 genes, respectively. Following AdHNF6 infection, HNF6 gene expression was 1.4-fold higher ( P = 0.02) in AdHNF6 SV40SM relative to AdHNF6 SV40LG cells, with a corresponding higher Foxa2 (4-fold), HNF1a (15-fold), and HNF4a (6-fold) gene expression in AdHNF6-SV40SM over AdHNF6-SV40LG. The net effects were upregulation of HNF6 target gene glucokinase and of Foxa2, HNF1a, and HNF4a target genes oatp1, ntcp, and mrp2 over AdLacZ control in both cells, but with higher levels in AdH6-SV40SM over AdH6-SV40LG of glucokinase, oatp1, ntcp, and mrp2 (by 1.8-, 3.4-, 2.4-, and 2.5-fold, respectively). In vivo, growth hormone-mediated increase in HNF6 expression was associated with similar higher upregulation of glucokinase and mrp2 in cholangiocytes from small vs. large BEC. Small and large BEC have a distinct profile of hepatocyte transcription factor and cognate target gene expression, as well as differential strength of response to transcriptional regulation, thus providing a potential molecular basis for their divergent function.
Bacterial cell products signal to mouse colonic nociceptive dorsal root ganglia neurons
Authors: Ochoa-Cortes Fernando , Ramos-Lomas Telma , Miranda-Morales Marcela , Spreadbury Ian , Ibeakanma Charles , Barajas-Lopez Carlos , Vanner Stephen
Published: June 2010

This study examined whether bacterial cell products that might gain access to the intestinal interstitium could activate mouse colonic nociceptive dorsal root ganglion (DRG) neurons using molecular and electrophysiological recording techniques. Colonic projecting neurons were identified by using the retrograde tracer fast blue and Toll-like receptor (TLR) 1, 2, 3, 4, 5, 6, 9, adapter proteins Md-1 and Md-2, and MYD88 mRNA expression was observed in laser-captured fast blue-labeled neurons. Ultrapure LPS 1 μg/ml phosphorylated p65 NF-κB subunits increased transcript for TNF-α and IL-1β and stimulated secretion of TNF-α from acutely dissociated DRG neurons. In current-clamp recordings from colonic DRG neurons, chronic incubation (24 h) of ultrapure LPS significantly increased neuronal excitability. In acute studies, 3-min superfusion of standard-grade LPS (3–30 μg/ml) reduced the rheobase by up to 40% and doubled action potential discharge rate. The LPS effects were not significantly different in TLR4 knockout mice compared with wild-type mice. In contrast to standard-grade LPS, acute application of ultrapure LPS did not increase neuronal excitability in whole cell recordings or afferent nerve recordings from colonic mesenteric nerves. However, acute application of bacterial lysate ( Escherichia coli NLM28) increased action potential discharge over 60% compared with control medium. Moreover, lysate also activated afferent discharge from colonic mesenteric nerves, and this was significantly increased in chronic dextran sulfate sodium salt mice. These data demonstrate that bacterial cell products can directly activate colonic DRG neurons leading to production of inflammatory cytokines by neurons and increased excitability. Standard-grade LPS may also have actions independent of TLR signaling.
Hypoxic relaxation of penile arteries: involvement of endothelial nitric oxide and modulation by reactive oxygen species
Authors: Prieto Dolores , Kaminski Pawel M. , Bagi Zsolt , Ahmad Mansoor , Wolin Michael S.
Published: June 2010

Although obesity-related cardiovascular disease and hypoxia are associated with erectile dysfunction, little is known about the direct effects of hypoxia on penile arteries. In the present study, the effects of acute hypoxia (Po2 = ∼10 Torr, 20 min) were investigated in isolated penile arteries to determine the influence of endothelium removal, nitric oxide (NO) synthase (NOS), cyclooxygenase (COX), NADPH oxidase, changes in reactive oxygen species (ROS), and a high-fat diet. Hypoxia-relaxed penile arteries contracted with phenylephrine by ∼50%. Relaxation to hypoxia and acetylcholine was reduced by endothelium removal and by inhibition of NOS ( Nω-nitro-l-arginine) and COX (indomethacin) but was enhanced by Tempol and by NADPH oxidase inhibition with apocynin and gp91ds-tat. Basal superoxide levels detected by lucigenin chemiluminescence were reduced by Tempol and gp91ds-tat and were enhanced by NOS blockade. Hypoxic relaxant responses were enhanced by catalase and ebselen. Exogenous peroxide evoked relaxations of penile arteries, which were partially inhibited by endothelium removal and by the inhibition of COX and extracellular signal-regulated mitogen-activated protein kinase (MAPK) but enhanced by p38 MAPK blockade. The NO-dependent component of relaxation to hypoxia was impaired in penile arteries from high-fat diet-fed, obese rats associated with increased superoxide production. Thus hypoxic relaxation of penile arteries is partially mediated by endothelial NO in a manner that is normally attenuated by endogenous ROS production. Obesity further increases superoxide production and impairs the influence of NO. Therefore, cardiovascular disease involving decreased NO bioavailability and/or enhanced ROS generation may contribute to erectile dysfunction through impairing the relaxation of penile arteries to hypoxia.
Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration
Authors: Wang Weidong , Li Chunling , Summer Sandra , Falk Sandor , Schrier Robert W.
Published: June 2010

The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 ± 0.1 in dDAVP+losartan (LSDL) vs. 1.1 ± 0.1 ml·100 g−1·day−1in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 ± 0.5 in LSDL vs. 6.8 ± 0.5 ml/min in LSD, P > 0.05). The urine output, however, was significantly increased in LSDL (2.5 ± 0.2 vs. 1.8 ± 0.2 ml·100 g−1·day−1, P < 0.05) in association with decreased urine osmolality (2,600 ± 83 vs. 3,256 ± 110 mosmol/kgH2O, P < 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 ± 6 vs. 176 ± 10% in LSD, P < 0.01), p-AQP2 (177 ± 13 vs. 214 ± 12% in LSD, P < 0.05), and AQP3 (134 ± 14 vs. 177 ± 11% in LSD, P < 0.05) in LSDL compared with LSD. The expressions of AQP1, the α1- and γ-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.
Vasopressin increases phosphorylation of Ser84 and Ser486 inSlc14a2collecting duct urea transporters
Authors: Hwang Shelly , Gunaratne Ruwan , Rinschen Markus M. , Yu Ming-Jiun , Pisitkun Trairak , Hoffert Jason D. , Fenton Robert A. , Knepper Mark A. , Chou Chung-Lin
Published: June 2010

Vasopressin-regulated urea transport in the renal inner medullary collecting duct (IMCD) is mediated by two urea channel proteins, UT-A1 and UT-A3, derived from the same gene ( Slc14a2) by alternative splicing. The NH2-terminal 459 amino acids are the same in both proteins. To study UT-A1/3 phosphorylation, we made phospho-specific antibodies to UT-A sequences targeting phospho-serines at positions 84 and 486, sites identified previously by protein mass spectrometry. Both antibodies proved specific, recognizing only the phosphorylated forms of UT-A1 and -A3. Immunoblotting of rat IMCD suspensions or whole inner medullas showed that the V2R-selective vasopressin analog 1-deamino-8-d-arginine vasopressin (dDAVP) increases phosphorylation at Ser84 (in UT-A1 and UT-A3) and Ser486 (in UT-A1) by about eightfold. Time course studies in rat IMCD suspensions showed maximum phosphorylation within 1 min of dDAVP exposure, consistent with the time course of vasopressin-stimulated phosphorylation of the vasopressin-sensitive water channel aquaporin-2 at Ser256. Confocal immunofluorescence in Brattleboro rat medullary tissue showed labeling limited to the IMCD, which increased markedly in response to dDAVP. Immuno-electron microscopy studies showed that both phosphorylated forms were present mainly in intracellular compartments in the presence of vasopressin. These studies demonstrate regulated phosphorylation of both UT-A1 and UT-A3 in response to vasopressin in a manner consistent with coordinate regulation of UT-A and aquaporin-2 in the renal IMCD. The findings add to prior evidence for vasopressin-induced phosphorylation of UT-A1, providing evidence that UT-A3 may be regulated by phosphorylation as well.
Effect of end-expiratory lung volume on upper airway collapsibility in sleeping men and women
Authors: Squier Samuel B. , Patil Susheel P. , Schneider Hartmut , Kirkness Jason P. , Smith Philip L. , Schwartz Alan R.
Published: June 2010

The relationship between changes in absolute end-expiratory lung volume (EELV) and collapsibility has not been rigorously quantified. We hypothesized that pharyngeal collapsibility varies inversely with absolute lung volume in sleeping humans during 1) conventional and 2) isovolume measurements of passive critical pressure (Pcrit). Eighteen healthy subjects (11 male, 7 female) slept in a negative pressure ventilator for measurements of pharyngeal collapsibility (Pcrit) during non-rapid eye movement sleep. EELV was 1) allowed to vary with changes in nasal pressure for conventional Pcrit measurements and 2) controlled by maintaining a fixed pressure difference across the respiratory system (PRS) from the nose to the body surface for isovolume Pcrit measurements at elevated EELV (PRS= +10 cmH2O), reduced EELV (PRS= −5 cmH2O), and functional residual capacity (FRC; PRS= 0 cmH2O). In each condition, the absolute EELV was determined and the corresponding Pcrit was derived from upper airway pressure-flow relationships. In the entire group, Pcrit varied inversely with EELV ( P < 0.001). Pcrit decreased as EELV increased from the conventional to the FRC isovolume condition by −3.5 ± 1.0 cmH2O/l ( P < 0.003). Subjects with a conventional Pcrit below −2 cmH2O exhibited greater reductions in EELV and correspondingly greater decreases in the FRC isovolume compared with the conventional Pcrit ( P < 0.001). The overall response, ΔPcrit/ΔEELV, was −2.0 ± 0.2 cmH2O/l ( P < 0.001) and did not differ between men and women ( P = 0.16). Nevertheless, men and women differed significantly in FRC (2.63 ± 0.16 vs. 1.88 ± 0.13 liters, P <0.05) and FRC isovolume Pcrit (−2.3 ± 0.8 vs. −7.2 ± 1.2 cmH2O, P < 0.05), implying that the men had larger lungs and more collapsible airways than the women. The ΔPcrit/ΔEELV response was independent of sex, conventional Pcrit, body mass index, and neck, waist, and hip circumferences. We conclude that Pcrit varies inversely with absolute EELV, which may lead to 1) an underestimation of the magnitude of quantitative differences in Pcrit across the spectrum from health (negative Pcrit) to disease (positive Pcrit) and 2) increases in sleep apnea susceptibility in obesity.
BCIRG 001 Molecular Analysis: Prognostic Factors in Node-Positive Breast Cancer Patients Receiving Adjuvant Chemotherapy
Authors: Dumontet Charles , Krajewska Maryla , Treilleux Isabelle , Mackey John R. , Martin Miguel , Rupin Mathieu , Lafanechère Laurence , Reed John C.
Published: June 2010

Purpose: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for node-positive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS).

Experimental Design: Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, β-tubulin isotypes II, III and IV, τ protein, and detyrosinated α tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique.

Results: In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and τ protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas τ protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation.

Conclusions: We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters τ protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy. Clin Cancer Res; 16(15); 3988–97. ©2010 AACR.