bluuebunny/crossref_metadata_2025 huggingface dataset:
RECONSTRUCTION OF SINGULAR SURFACES BY SHAPE SENSITIVITY ANALYSIS AND LEVEL SET METHOD
Authors: BAL GUILLAUME , REN KUI
Published: August 2006

We consider the reconstruction of singular surfaces from the over-determined boundary conditions of an elliptic problem. The problem arises in optical and impedance tomography, where void-like structure or cracks may be modeled as diffusion processes supported on co-dimension one surfaces. The reconstruction of such surfaces is obtained theoretically and numerically by combining a shape sensitivity analysis with a level set method. The shape sensitivity analysis is used to define a velocity field, which allows us to update the surface while decreasing a given cost function, which quantifies the error between the prediction of the forward model and the measured data. The velocity field depends on the geometry of the surface and the tangential diffusion process supported on it. The latter process is assumed to be known in this paper. The level set method is next applied to evolve the surface in the direction of the velocity field. Numerical simulations show how the surface may be reconstructed from noisy estimates of the full, or local, Neumann-to-Dirichlet map.
TUMOR-IMMUNE SYSTEM INTERACTION: MODELING THE TUMOR-STIMULATED PROLIFERATION OF EFFECTORS AND IMMUNOTHERAPY
Authors: D'ONOFRIO A.
Published: August 2006

Tumoral dynamics and antitumor immunotherapies are likely to be influenced by the modalities of interaction between tumor cells and immune system effectors, and by the inter-effectors interactions. Within the framework of the theory of competing populations, we study here the influence of the proliferation response of effectors to tumor burden, and of cooperation and/or competition between immune system effectors, by means of three inter-related bi-dimensional meta-models. After studying their null-clines, we study the location and the local stability of the equilibria. Then, we investigate the existence and, in some cases, the uniqueness of stable limit cycles. The condition for the global asymptotically stable eradication under constant or slightly variable periodic immunotherapy is given. Finally, implications of strong saturation in the effectors ability to kill tumor cells are discussed.
THREE TIME-DOMAIN COMPUTATIONAL MODELS FOR QUASI-STANDING NONLINEAR ACOUSTIC WAVES, INCLUDING HEAT PRODUCTION
Authors: VANHILLE CHRISTIAN , CAMPOS-POZUELO CLEOFÉ
Published: August 2006

Applications of high-amplitude acoustic or ultrasonic waves in industrial processing require a good knowledge of the nonlinear pressure field, as well as the heat produced by the wave. In this article a new time-domain algorithm solving a second-order nonlinear wave equation written in Lagrangian coordinates and valid for any fluid is presented. The new model is compared with two others which were previously developed, corresponding to the two other possible physical approaches. This paper discusses the limits of application of every approach and the suitability of every one to model nonlinear acoustic waves in resonators. Conclusions about the applicability of the physical models are given. The time-domain character of the models allows the development of a new algorithm to calculate the temperature evolution inside a resonator due to acoustic losses. This algorithm is presented here and applied to strongly nonlinear waves for which the nonlinear attenuation is dominant. Several kinds of time functions for excitation can be considered in the models. The strongly nonlinear resonator response to a short pulsed signal is analyzed to show the efficiency of the time-domain numerical model.
TREATMENT OF RANK DEFICIENCY IN ACOUSTICS USING SVD
Authors: CHEN J. T. , CHEN I. L. , CHEN K. H.
Published: August 2006

In this paper, we proposed a unified formulation to explain the reason why spurious eigensolution occurs in the eigenproblem of interior acoustics using the real-part and imaginary-part BEMs and why fictitious frequency occurs in exterior acoustics using the complex-valued BEM. Both the two problems stem from the rank deficiency of the influence matrix. Based on the circulant properties and degenerate kernels, an analytical study in a discrete system for a circular cavity is conducted. The Fredholm alternative theorem is employed to study the rank-deficiency problems in conjunction with singular value decomposition updating technique. The spurious and fictitious boundary modes are found to locate in the column vectors of left unitary matrix. Also, the effects of different types of boundary condition on the spurious and fictitious solutions using direct and indirect methods are discussed. The mathematical and physical meanings for the nontrivial boundary solution in spurious eigensolution and fictitious frequency are explained. Numerical experiments are found to agree with the analytical predictions.
A TIME DOMAIN METHOD FOR MODELING VISCOACOUSTIC WAVE PROPAGATION
Authors: GROBY JEAN-PHILIPPE , TSOGKA CHRYSOULA
Published: August 2006

In many applications, and in particular in seismology, realistic propagation media disperse and attenuate waves. This dissipative behavior can be taken into account by using a viscoacoustic propagation model, which incorporates a complex and frequency-dependent viscoacoustic modulus in the constitutive relation. The main difficulty then lies in finding an efficient way to discretize the constitutive equation as it becomes a convolution integral in the time domain. To overcome this difficulty the usual approach consists in approximating the viscoacoustic modulus by a low-order rational function of frequency. We use here such an approximation and show how it can be incorporated in the velocity-pressure formulation for viscoacoustic waves. This formulation is coupled with the fictitious domain method which permits us to model efficiently diffraction by objects of complicated geometry and with the Perfectly Matched Layer Model which allows us to model wave propagation in unbounded domains. The space discretization of the problem is based on a mixed finite element method and for the discretization in time a 2nd order centered finite difference scheme is employed. Several numerical examples illustrate the efficiency of the method.
SOLUTIONS OF THE HELMHOLTZ EQUATION CONCENTRATED NEAR THE AXIS OF A DEEP-WATER WAVEGUIDE IN A RANGE-DEPENDENT MEDIUM
Authors: GRIGORIEVA NATALIE S. , FRIDMAN GREGORY M.
Published: August 2006

This paper examines a two-dimensional deep-water waveguide in a range-dependent medium. Solutions of the homogeneous Helmholtz equation concentrated near the waveguide axis and which decrease exponentially outside a strip containing the axis are constructed. These solutions have the form of exponentials multiplied by parabolic cylinder functions whose arguments are an infinite series in powers of ω-1/2, where ω is a cyclic frequency. Coefficients of these series are found from a recurrent system of differential equations up to terms allowing to get a residual (difference between the left-hand side of the Helmholtz equation and zero) of order ω-1/2. Arbitrary constants of general solutions of arising differential equations are calculated going over to the limiting case of a range-independent medium. Numerical simulations are carried out for a deterministic model of a range-dependent ocean, where the range-dependence results for change in geographic location. Parameters of this medium model are matched with the AET experiment.
CLASSIFICATION OF OBJECTS IN AN ACOUSTIC WAVEGUIDE BY INVERSION OF THE FARFIELD DATA
Authors: LEE DOO-SUNG , GILBERT R. P. , ZEEV NOAM
Published: August 2006

In this paper we investigate the unknown body problem in a waveguide. The Rayleigh conjecture states that every point on an illuminated body radiates sound from that point as if the point lies on its tangent sphere. This conjecture is the cornerstone of the intersecting canonical body approximation ICBA for solving the unknown body inverse problem. Therefore, the use of the ICBA requires that an analytical solution be known exterior to the sphere in the waveguide, which leads us to analytically compute the exterior solution for a sphere between two parallel plates. A least-squares matching of theoretical acoustic fields against the measured, scattered field permits a reconstruction of the unknown object.
SOUND TRANSMISSION AND SPATIAL COHERENCE IN SELECTED SHALLOW-WATER AREAS: MEASUREMENTS AND THEORY
Authors: CAREY WILLIAM M. , LYNCH JAMES F. , SIEGMANN WILLIAM L. , ROZENFELD ILYA , SPERRY BRIAN J.
Published: August 2006

Experiments from several shallow-water areas are summarized. Coherent sound transmission results, particularly wavenumber spectra, are compared to range-dependent calculations that use oceanographic and geophysical characteristics from measurements and archives as bounded inputs to the propagation codes. In general excellent agreement was obtained between the measured and calculated results for both narrowband and broadband transmissions between 50 Hz and 1 kHz to ranges of 40 km. A relative signal gain (RSG) method for the estimation of horizontal coherence length was applied to measured RSG results and yielded coherence lengths on the order of 30λ at 400 Hz at distances of 40 km. Perturbation theory was applied to the shallow-water waveguide under the condition of adiabatic normal modes and expressions were derived for the phase structure function that was simplified by the use of Gaussian correlation functions. These analytical results, along with estimates of the variances of the environmental variables permitted the estimation of the coherence function and the RSG. The calculated coherence function and RSG were found to be consistent with measured RSG and replica correlation results. The fluctuations in the oceanic water volume were found to be the dominant factor in the loss of coherence.
SEMANTICS-BASED DYNAMIC WEB SERVICE COMPOSITION
Authors: FUJII KEITA , SUDA TATSUYA
Published: August 2006

This paper presents a semantics-based dynamic service composition architecture that composes an application through combining distributed components based on the semantics of the components. This architecture consists of a component model called Component Service Model with Semantics (CoSMoS), a middleware called Component Runtime Environment (CoRE), and a service composition mechanism called Semantic Graph based Service Composition (SeGSeC). CoSMoS represents the semantics of components. CoRE provides interfaces to discover and access components modeled by CoSMoS. SeGSeC composes an application by discovering components through CoRE, and synthesizing a workflow of the application based on the semantics of the components modeled by CoSMoS.

This paper describes the latest design of the semantics-based dynamic service composition architecture, and also illustrates the implementation of the architecture based on the Web Service standards, i.e. WSDL, RDF, SOAP, and UDDI. The Web Service based implementation of the architecture allows existing Web Services to migrate onto the architecture without reimplementation. It also simplifies the development and deployment of a new Web Service on the architecture by automatically generating the necessary description files (i.e. WSDL and RDF files) of the Web Service from its runtime binary (i.e. a Java class file).
NON-INTRUSIVE MONITORING OF SERVICE-BASED SYSTEMS
Authors: SPANOUDAKIS GEORGE , MAHBUB KHALED
Published: August 2006

This paper presents a framework for monitoring the compliance of systems composed of Web-services with requirements set for them at runtime. This framework assumes systems composed of Web-services which are co-coordinated by a service composition process expressed in BPEL and uses event calculus to specify the requirements to be monitored. These requirements may include behavioral properties of a system which are automatically extracted from the specification of its composition process in BPEL and/or assumptions that system providers can specify in terms of events extracted from this specification.
A LAYERED FRAMEWORK FOR CONNECTING CLIENT OBJECTIVES AND RESOURCE CAPABILITIES
Authors: DAN ASIT , RANGANATHAN KAVITHA , DUMITRESCU CATALIN L. , RIPEANU MATEI
Published: August 2006

In large-scale, distributed systems such as Grids, an agreement between a client and a service provider specifies service level objectives both as expressions of client requirements and as provider assurances. From an application perspective, these objectives should be expressed in a high-level, service or application-specific manner rather than requiring clients to detail the necessary resources. Resource providers on the other hand, expect low-level, resource-specific performance criteria that are uniform across applications and can be easily interpreted and provisioned.

This paper presents a framework for service management that addresses this gap between high-level specification of client performance objectives and existing resource management infrastructures. The paper identifies three levels of abstraction for resource requirements a service provider needs to manage, namely: detailed specification of raw resources, virtualization of heterogeneous resources as abstract resources, and performance objectives at an application level. The paper also identifies three key functions for managing service-level agreements, namely: translation of resource requirements across abstraction layers, arbitration in allocating resources to client requests, and aggregation and allocation of resources from multiple lower-level resource managers. One or more of these key functions may be present at each abstraction layer of a service-level manager. Thus, layering and the composition of these functions across abstraction layers enables modeling of a wide array of management scenarios. The framework we present uses service metadata and/or service performance models to map client requirements to resource capabilities, uses business value associated with objectives to arbitrate between competing requests, and allocates resources based on previously negotiated agreements. We instantiate this framework for three different scenarios and explain how the architectural principles we introduce are used in the real-word.
CONCRETE SOLUTIONS FOR WEB SERVICES ADAPTABILITY USING POLICIES AND ASPECTS
Authors: TOMAZ RICARDO FERRAZ , HMIDA MEHDI BEN , MONFORT VALERIE
Published: August 2006

Traditional middleware is usually developed on monolithic and non-evolving entities, resulting in a lack of flexibility and interoperability. Among current architectures, Service Oriented Architectures aim to easily develop more adaptable Information Systems. Most often, Web Service is the fitted technical solution which provides the required loose coupling to achieve such architectures. However, there is still much to be done in order to obtain a genuinely flawless Web Service, and current market implementations still do not provide adaptable Web Service behavior depending on the service contract. In this paper, we present our two last years of work toward a more adaptable SOA. We proposed two approaches that consider Aspect Oriented Programming (AOP) as a new design solution for Web Services. The two approaches enable us to glue new non-functional behaviors to a Web Service without going back to modify, recompile, retest and finally redeploy it.
A SERVICE-ORIENTED APPROACH TO ENFORCE GRID RESOURCE ALLOCATIONS
Authors: SANDHOLM THOMAS , GARDFJÄLL PETER , ELMROTH ERIK , MULMO OLLE , JOHNSSON LENNART
Published: August 2006

We present the SweGrid Accounting System (SGAS) — a decentralized and standards-based system for Grid resource allocation enforcement that has been developed with an emphasis on a uniform data model and easy integration into existing scheduling and workload management software.

The system has been tested at the six high-performance computing centers comprising the SweGrid computational resource, and addresses the need for soft, real-time quota enforcement across the SweGrid clusters.

The SGAS framework is based on state-of-the-art Web and Grid services technologies. The openness and ubiquity of Web services combined with the fine-grained resource control and cross-organizational security models of Grid services proved to be a perfect match for the SweGrid needs. Extensibility and customizability of policy implementations for the three different parties that the system serves (the user, the resource manager, and the allocation authority) are key design goals. Another goal is end-to-end security and single sign-on, to allow resources to reserve allocations and charge for resource usage on behalf of the user.

We conclude this paper by illustrating the policy customization capabilities of SGAS in a simulated setting, where job streams are shaped using different modes of allocation policy enforcement. Finally, we discuss some of the early experiences from the production system.
FLASH MEMORY LOCK MANAGEMENT FOR PORTABLE INFORMATION SYSTEMS
Authors: BYUN SIWOO , HUH MOONHAENG , HWANG HOYOUNG
Published: August 2006

Flash memory is becoming a major database storage in building embedded systems or portable devices because of its non-volatile, shock-resistant, power-economic nature, and fast access time for read operations. Flash memory, however, should be erased before it can be rewritten and the erase and write operations are very slow as compared to main memory. Due to this drawback, traditional database management schemes are not easy to apply directly to flash memory database for portable devices. Therefore, we improve the traditional schemes and propose a new scheme called Flash Two Phase Locking (F2PL) scheme for efficient transaction processing in a flash memory database environment. F2PL achieves high transaction performance by exploiting the notion of the Alternative Version Coordination which allows previous version reads and efficiently handles slow write/erase operations in lock management processes. We also propose a simulation model to show the performance of F2PL. Based on the results of the performance evaluation, we conclude that F2PL scheme outperforms the traditional schemes.
IMAGE GUIDED NOISE TOMOGRAPHY FOR INCREASED SPECIFICITY OF MAGNETIC RESONANCE IMAGING
Authors: REZA SHAHED , BOSMAN GIJS , DUENSING GEORGE R. , HUANG FENG , LIMKEMAN MARK , SAYLOR CHARLES
Published: August 2006

A method for increasing the specificity of an MR image using noise correlation measurements is presented. From an MR image different regions within the body are identified based on contrast. Noise signals measured at the ports of the experimental setup are functions of the conductivity at each region and the sensitivity map of the field probes. For a simulated sensitivity map, the ratio of conductivities of two regions of a phantom containing saline and distilled water was determined from the measured noise correlation at the ports.
INTERFERER REJECTION IMPROVED BY NOISE IN ULTRA-WIDEBAND TELECOMMUNICATIONS
Authors: FIORINA JOCELYN , ROUSSEAU DAVID , CHAPEAU-BLONDEAU FRANÇOIS
Published: August 2006

Ultra-wideband technology uses baseband transmission of low-power ultra-short information-bearing impulses, and represents a promising approach for very-high speed wireless communications with multiple access, as well as for low-rate high-accuracy positioning systems. The first demonstrations of the huge potential of ultra-wideband were based on hypotheses of perfect power control and multiuser interferences modeled as white Gaussian noise. Here, by explicitly modeling the interference with an external impulse signal, we demonstrate the possibility of improving the rejection of the interferer thanks to a constructive action of the noise. This is interpreted as a novel instance of the phenomenon of stochastic resonance or improvement by noise in signal processing.
Assessment and Diagnosis of Personality Disorder: Perennial Issues and an Emerging Reconceptualization
Authors: Clark Lee Anna
Published: August 2006

Abstract  This chapter reviews recent (2000–2005) personality disorder (PD) research, focusing on three major domains: assessment, comorbidity, and stability. (a) Substantial evidence has accrued favoring dimensional over categorical conceptualization of PD, and the five-factor model of personality is prominent as an integrating framework. Future directions include assessing dysfunction separately from traits and learning to utilize collateral information. (b) To address the pervasiveness and extent of comorbidity, researchers have begun to move beyond studying overlapping pairs or small sets of disorders and are developing broader, more integrated common-factor models that cross the Axis I–Axis II boundary. (c) Studies of PD stability have converged on the finding that PD features include both more acute, dysfunctional behaviors that resolve in relatively short periods, and maladaptive temperamental traits that are relatively more stable—similar to normal-range personality traits—with increasing stability until after 50 years of age. A new model for assessing PD—and perhaps all psychopathology—emerges from integrating these interrelated reconceptualizations.
The Elaboration of Personal Construct Psychology
Authors: Walker Beverly M. , Winter David A.
Published: August 2006

Abstract  More than half a century has passed since the publication of George Kelly's (1955/1991) The Psychology of Personal Constructs. This review considers the elaboration of personal construct psychology (PCP) during this time, both by Kelly and by others who developed his ideas. Advances to the theory have principally concerned implicative relationships between constructs, construing of the self, social relationships, emotions, links with other approaches, and supporting research. With regard to methods of assessment of construing, major developments have occurred in both repertory grid and nongrid techniques, such as laddering. The principal advances in the applications of PCP have been in the clinical, educational, and organizational fields, but have by no means been limited to these areas. It can be concluded that PCP has met Kelly's own design specifications for a useful theory and that PCP can perhaps anticipate at least another half-century of elaboration.
Work Group Diversity
Authors: van Knippenberg Daan , Schippers Michaéla C.
Published: August 2006

Abstract  Work group diversity, the degree to which there are differences between group members, may affect group process and performance positively as well as negatively. Much is still unclear about the effects of diversity, however. We review the 1997–2005 literature on work group diversity to assess the state of the art and to identify key issues for future research. This review points to the need for more complex conceptualizations of diversity, as well as to the need for more empirical attention to the processes that are assumed to underlie the effects of diversity on group process and performance and to the contingency factors of these processes.
An Interactionist Perspective on the Socioeconomic Context of Human Development
Authors: Conger Rand D. , Donnellan M. Brent
Published: August 2006

This article addresses the relationship between socioeconomic status (SES), family processes, and human development. The topic is framed as part of the general issue of health disparities, which involves the oft-observed positive relationship between SES and the cognitive, social, emotional, and physical well-being of adults and children. A review of recent research and theory identifies three general theoretical approaches that provide possible explanations for the association between SES and individual development: the social causation, social selection, and interactionist perspectives. Empirical evidence demonstrates support for the social causation view that SES affects families and the development of children in terms of both family stress processes (the family stress model) and family investments in children (the family investment model). However, there also is empirical support for the social selection argument that individual characteristics lead to differences in SES. Especially important, recent research is consistent with an interactionist approach, which proposes a dynamic relationship between SES and developmental change over time. Drawing on the combined set of research findings, the article concludes with the description of an interactionist model that serves as a heuristic for future studies of the links among SES, parenting behaviors, and child development.
The Neurobiology of Stress and Development
Authors: Gunnar Megan , Quevedo Karina
Published: August 2006

Abstract  Stress is a part of every life to varying degrees, but individuals differ in their stress vulnerability. Stress is usefully viewed from a biological perspective; accordingly, it involves activation of neurobiological systems that preserve viability through change or allostasis. Although they are necessary for survival, frequent neurobiological stress responses increase the risk of physical and mental health problems, perhaps particularly when experienced during periods of rapid brain development. Recently, advances in noninvasive measurement techniques have resulted in a burgeoning of human developmental stress research. Here we review the anatomy and physiology of stress responding, discuss the relevant animal literature, and briefly outline what is currently known about the psychobiology of stress in human development, the critical role of social regulation of stress neurobiology, and the importance of individual differences as a lens through which to approach questions about stress experiences during development and child outcomes.
The Close Relationships of Lesbians and Gay Men
Authors: Peplau Letitia Anne , Fingerhut Adam W.
Published: August 2006

Abstract  This article reviews empirical studies of same-sex couples in the United States, highlighting consistent findings, drawing comparisons to heterosexual couples, and noting gaps in available research. U.S. Census data indicate that there were more than 600,000 same-sex couples living together in 2000. Research about relationship formation, the division of household labor, power, satisfaction, sexuality, conflict, commitment, and relationship stability is presented. Next, we highlight three recent research topics: the legalization of same-sex relationships through civil unions and same-sex marriage, the experiences of same-sex couples raising children, and the impact of societal prejudice and discrimination on same-sex partners. We conclude with comments about the contributions of empirical research to debunking negative stereotypes of same-sex couples, testing the generalizability of theories about close relationships, informing our understanding of gender and close relationships, and providing a scientific basis for public policy.
The Development of Coping
Authors: Skinner Ellen A. , Zimmer-Gembeck Melanie J.
Published: August 2006

Abstract  Research on coping during childhood and adolescence is distinguished by its focus on how children deal with actual stressors in real-life contexts. Despite burgeoning literatures within age groups, studies on developmental differences and changes have proven difficult to integrate. Two recent advances promise progress toward a developmental framework. First, dual-process models that conceptualize coping as “regulation under stress” establish links to the development of emotional, attentional, and behavioral self-regulation and suggest constitutional underpinnings and social factors that shape coping development. Second, analyses of the functions of higher-order coping families allow identification of corresponding lower-order ways of coping that, despite their differences, are developmentally graded members of the same family. This emerging framework was used to integrate 44 studies reporting age differences or changes in coping from infancy through adolescence. Together, these advances outline a systems perspective in which, as regulatory subsystems are integrated, general mechanisms of coping accumulate developmentally, suggesting multiple directions for future research.
Work and Vocational Psychology: Theory, Research, and Applications
Authors: Fouad Nadya A.
Published: August 2006

Abstract  Work is integral to human functioning, and all psychologists need to understand the role of work in people's lives. Understanding factors influencing work choices and helping individuals effectively make career decisions is the focus of vocational psychologists. However, external changes, such as shifts in the economy and labor force, as well as initiatives within the field are challenging the assumptions within vocational psychology. This chapter reviews the empirical work since 1995 in four areas: (a) what factors influence career choices, (b) how people make career decisions, (c) how context influences career choices, and (d) effective interventions for help with the first three questions. The review focuses first on vocational psychology's rich tradition of theoretically driven research, and then discusses research in career development that crosses a number of theoretical approaches, and finally identifies the assumptions in the field and questions for future examination.
Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships
Authors: Keely Stephen J. , Scharl Michael M. , Bertelsen Lone S. , Hagey Lee R. , Barrett Kim E. , Hofmann Alan F.
Published: August 2006

Bile acid epimers and side-chain homologues are present in the human colon. To test whether such bile acids possess secretory activity, cultured T84 colonic epithelial cells were used to quantify the secretory properties of synthetic epimers and homologues of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). In our study, chloride secretion was measured as changes in short-circuit current (Δ Isc, in μA/cm2) with the use of voltage-clamped monolayers of T84 cells mounted in Ussing chambers. Bile acids were added at 0.5 mM, a concentration that did not alter transepithelial resistance. Data were expressed as peak Δ Isc(means ± SD). When added bilaterally, DCA stimulated a Δ Iscresponse of 15.7 ± 12.5 μA/cm2. The 12β-OH epimer of DCA was less potent (Δ Isc= 8.0 ± 1.7 μA/cm2), whereas its 3β-OH epimer had no effect. CDCA stimulated secretion (Δ Isc= 8.2 ± 5.5 μA/cm2), whereas both its 7β-OH and 3β-OH epimers were inactive, as was lithocholic acid. HomoDCA (1 additional side-chain carbon) was active (Δ Isc= 7.8 ± 4.8 μA/cm2), whereas norDCA (1 fewer carbon) and dinorDCA (2 fewer carbons) were not. Taurine conjugates of DCA and CDCA stimulated secretion (Δ Isc= 12.3 ± 7.5 and 8.8 ± 4.8 μA/cm2, respectively) from the basolateral side but not the apical side. Uptake of taurine conjugates from the basolateral but not the apical side was shown by mass spectrometry. These studies indicate marked structural specificity for bile acid-induced chloride secretion and show that modification of bile acid structure by colonic bacteria modulates the secretory properties of these endogenous secretagogues.
Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig
Authors: Moeser Adam J. , Klok Carin Vander , Ryan Kathleen A. , Wooten Jenna G. , Little Dianne , Cook Vanessa L. , Blikslager Anthony T.
Published: August 2006

Weaning in the piglet is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Although stress is thought to play a role in postweaning intestinal disease, the mechanisms by which stress influences intestinal pathophysiology in the weaned pig are not understood. The objectives of these experiments were to investigate the impact of weaning on gastrointestinal health in the pig and to assess the role of stress signaling pathways in this response. Nineteen-day-old pigs were weaned, and mucosal barrier function and ion transport were assessed in jejunal and colonic tissues mounted on Ussing chambers. Weaning caused marked disturbances in intestinal barrier function, as demonstrated by significant ( P < 0.01) reductions in transepithelial electrical resistance and increases in intestinal permeability to [3H]mannitol in both the jejunum and colon compared with intestinal tissues from age-matched, unweaned control pigs. Weaned intestinal tissues exhibited increased intestinal secretory activity, as demonstrated by elevated short-circuit current that was sensitive to treatment with tetrodotoxin and indomethacin, suggesting activation of enteric neural and prostaglandin synthesis pathways in weaned intestinal tissues. Western blot analyses of mucosal homogenates showed increased expression of corticotrophin-releasing factor (CRF) receptor 1 in the jejunum and colon of weaned intestinal tissues. Pretreatment of pigs with the CRF receptor antagonist α-helical CRF(9–41), which was injected intraperitoneally 30 min prior to weaning, abolished the stress-induced mucosal changes. Our results indicate that weaning stress induces mucosal dysfunction mediated by intestinal CRF receptors and activated by enteric nerves and prostanoid pathways.
Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin
Authors: Lim Do Y. , Jeong Yoonhwa , Tyner Angela L. , Park Jung H. Y.
Published: August 2006

Luteolin is 3′,4′,5,7-tetrahydroxyflavone found in celery, green pepper, and perilla leaf that inhibits tumorigenesis in animal models. We examined luteolin-mediated regulation of cell cycle progression and apoptosis in the HT-29 human colon cancer cell line. Luteolin decreased DNA synthesis and viable HT-29 cell numbers in a concentration-dependent manner. It inhibited cyclin-dependent kinase (CDK)4 and CDK2 activity, resulting in G1 arrest with a concomitant decrease of phosphorylation of retinoblastoma protein. Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity ( P < 0.05) observed in cells treated with 40 μmol/l luteolin. Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment, although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspases 3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21CIP1/WAF1, survivin, Mcl-1, Bcl-xL, and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells. We demonstrate that luteolin promotes both cell cycle arrest and apoptosis in the HT-29 colon cancer cell line, providing insight about the mechanisms underlying its antitumorigenic activities.
Recognition of intestinal epithelial HIF-1α activation by Pseudomonas aeruginosa
Authors: Patel Nachiket J. , Zaborina Olga , Wu Licheng , Wang Yingmin , Wolfgeher Donald J. , Valuckaite Vesta , Ciancio Mae J. , Kohler Jonathan E. , Shevchenko Olga , Colgan Sean P. , Chang Eugene B. , Turner Jerrold R. , Alverdy John C.
Published: August 2006

Human intestinal epithelial cell monolayers (Caco-2) subjected to hypoxia and reoxygenation release soluble factors into the apical medium that activate the virulence of the opportunistic pathogen Pseudomonas aeruginosa to express the potent barrier-dysregulating protein PA-I lectin/adhesin. In this study, we defined the role of hypoxia-inducible factor (HIF)-1α in this response. We tested the ability of medium from Caco-2 cells with forced expression of HIF-1α to increase PA-I expression in P. aeruginosa and found that medium from Caco-2 cells overexpressing HIF-1α increased PA-I expression compared with medium from control cells ( P < 0.001, ANOVA). To identify the components responsible for this response, medium was fractionated by molecular weight and subjected to mass spectroscopy, which identified adenosine as the possible mediator. Both adenosine and its immediate downstream metabolite inosine induced PA-I expression in P. aeruginosa in a dose-dependent fashion. Because inosine was not detectable in the medium of Caco-2 cells exposed to hypoxia or overexpressing HIF-1α, we hypothesized that P. aeruginosa itself might metabolize adenosine to inosine. Using mutant and parental strains of P. aeruginosa, we demonstrated that P. aeruginosa metabolized adenosine to inosine via adenosine deaminase and that the conditioned medium enhanced the extracellular accumulation of inosine. Together, these results provide evidence that P. aeruginosa can recognize and respond to extracellular end products of intestinal hypoxia that are released after activation of HIF-1α. The ability of P. aeruginosa to metabolize adenosine to inosine may represent a subversive microbial virulence strategy that deprives the epithelium of the cytoprotective actions of adenosine.
Prednisolone-induced Ca2+malabsorption is caused by diminished expression of the epithelial Ca2+channel TRPV6
Authors: Huybers Sylvie , Naber Ton H. J. , Bindels René J. M. , Hoenderop Joost G. J.
Published: August 2006

Glucocorticoids, such as prednisolone, are often used in clinic because of their anti-inflammatory and immunosuppressive properties. However, glucocorticoids reduce bone mineral density (BMD) as a side effect. Malabsorption of Ca2+in the intestine is supposed to play an important role in the etiology of low BMD. To elucidate the mechanism of glucocorticoid-induced Ca2+malabsorption, the present study investigated the effect of prednisolone on the expression and activity of proteins responsible for active intestinal Ca2+absorption including the epithelial Ca2+channel TRPV6, calbindin-D9K, and the plasma membrane ATPase PMCA1b. Therefore, C57BL/6 mice received 10 mg/kg body wt prednisolone daily by oral gavage for 7 days and were compared with control mice receiving vehicle only. An in vivo45Ca2+absorption assay indicated that intestinal Ca2+absorption was diminished after prednisolone treatment. We showed decreased duodenal TRPV6 and calbindin-D9KmRNA and protein abundance in prednisolone-treated compared with control mice, whereas PMCA1b mRNA levels were not altered. Importantly, detailed expression studies demonstrated that in mice these Ca2+transport proteins are predominantly localized in the first 2 cm of the duodenum. Furthermore, serum Ca2+and 1,25-dihydroxyvitamin D3[1,25(OH)2D3] concentrations remained unchanged by prednisolone treatment. In conclusion, these data suggest that prednisolone reduces the intestinal Ca2+absorption capacity through diminished duodenal expression of the active Ca2+transporters TRPV6 and calbindin-D9Kindependent of systemic 1,25(OH)2D3.
Identification of apoptotic genes mediating TGF-β/Smad3-induced cell death in intestinal epithelial cells using a genomic approach
Authors: Cao Yanna , Chen Lu , Zhang Weili , Liu Yan , Papaconstantinou Harry T. , Bush Craig R. , Townsend Courtney M. , Thompson E. Aubrey , Ko Tien C.
Published: August 2006

Transforming growth factor (TGF)-β-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-β inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-β-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-β-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-β/Smad3. Total RNA samples were analyzed using Affymetrix oligonucleotide microarrays. We found that TGF-β regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Furthermore, TGF-β activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-β induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-β-induced apoptosis in RIE-1/Smad3 cells.
A naturally occurring point mutation in the rat aquaporin 5 gene, influencing its protein production by and secretion of water from salivary glands
Authors: Murdiastuti Kwartarini , Purwanti Nunuk , Karabasil Mileva Ratko , Li Xuefei , Yao Chenjuan , Akamatsu Tetsuya , Kanamori Norio , Hosoi Kazuo
Published: August 2006

A greater than twofold diversity in the expression level of aquaporin 5 (AQP5) has been observed in the membrane fraction of the submandibular gland (SMG) in Sprague-Dawley rats (Murdiastuti K, Miki O, Yao C, Parvin MN, Kosugi-Tanaka C, Akamatsu T, Kanamori N, and Hosoi K. Pflügers Arch 445: 405–412, 2002). In the present study, breeding between brother and sister rats was repeated within high AQP5 producers and low ones to obtain inbred offspring. High- and low-producer rats from 3rd to 18th generations were used for experiments. By Western blotting, levels of AQP5 proteins in the parotid and lacrimal glands, and lungs were all low in low producers, whereas they were all high in high producers, implying genetic variations of the gene for this water channel. Despite this implication, AQP5 mRNA levels were almost the same between the two groups by Northern blotting, suggesting the irrelevance of transcriptional regulation for this diversity. AQP5 cDNAs from the SMGs of the two groups were sequenced. The nucleotide sequence of AQP5 cDNA from low producers indicated the existence of a point mutation at nt 308 (G308A), leading to a replacement of 103Gly with 103Asp in the third transmembrane domain, but no alteration was detected in the Kozak area. The existence of such a mutation was confirmed by the assessment of genomic DNA also. This mutation may have resulted in an abnormal membrane insertion or ineffective trafficking of AQP5, since the rats having this mutation showed extremely low membrane expression of AQP5 in the SMG acinar cells and decreased water secretion from their salivary glands.
Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates
Authors: de Chantal Marilyn , Diodati Jean G. , Nasmith James B. , Amyot Robert , LeBlanc A. Robert , Schampaert Erick , Pharand Chantal
Published: August 2006

ST-segment depression is commonly seen in patients with acute coronary syndromes. Most authors have attributed it to transient reductions in coronary blood flow due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and dynamic focal vasospasm at the site of coronary artery stenosis. However, ST-segment depression was never reproduced in classic animal models of coronary stenosis without the presence of tachycardia. We hypothesized that ST-segment depression occurring during acute coronary syndromes is not entirely explained by changes in epicardial coronary artery resistance and thus evaluated the effect of a slow, progressive epicardial coronary artery occlusion on the ECG and regional myocardial blood flow in anesthetized pigs. Slow, progressive occlusion over 72 min (SD 27) of the left anterior descending coronary artery in 20 anesthetized pigs led to a 90% decrease in coronary blood flow and the development of ST-segment elevation associated with homogeneous and transmural myocardial blood flow reductions, confirmed by microspheres and myocardial contrast echocardiography. ST-segment depression was not observed in any ECG lead before the development of ST-segment elevation. At normal heart rates, progressive epicardial stenosis of a coronary artery results in myocardial ischemia associated with homogeneous, transmural reduction in regional myocardial blood flow and ST-segment elevation, without preceding ST-segment depression. Thus, in coronary syndromes with ST-segment depression and predominant subendocardial ischemia, factors other than mere increases in epicardial coronary resistance must be invoked to explain the heterogeneous parietal distribution of flow and associated ECG changes.
Altered allergen-induced eosinophil trafficking and physiological dysfunction in airways with preexisting virus-induced injury
Authors: Sorkness Ronald L. , Herricks Kathryn M. , Szakaly Renee J. , Lemanske Robert F. , Rosenthal Louis A.
Published: August 2006

Although both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of air space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after six weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the air space. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways before the allergen exposures.
Variations in apparent mass of mammalian fast-type myosin light chains correlate with species body size, from shrew to elephant
Authors: Bicer Sabahattin , Reiser Peter J.
Published: August 2006

A recent study (Bicer S and Reiser PJ. J Muscle Res Cell Motil 25: 623–633, 2004) suggested considerable variation in the apparent molecular mass (Ma), deduced from electrophoretic mobility, in fast-type myosin light chains (MLCF), especially MLC1F, among mammalian species. Furthermore, there was an indication that MLC1F Magenerally correlates with species body mass, over an ∼4,000-fold range in body mass. The results also suggested that Maof other low-molecular-weight myofibrillar proteins is less variable and not as strongly correlated with body mass among the same species. The objective of this study was to test the hypotheses that the Maof MLCs does, in fact, vary and correlate with species body mass. The electrophoretic mobilities of MLCF isoforms from 19 species, varying in size ∼500,000-fold, were quantitated. The results confirm that the Maof MLC1F and MLC2F vary significantly among mammals, spanning a very broad range in body mass; the MLC1F Mavaries more than that of other low-molecular-weight myofibrillar proteins; and there is a significant correlation between species body mass and MLC1F Ma. Differences in MLC1F Maamong five species can be accounted for by differences in the reported amino acid sequence, especially the length of a common polyalanine region near the NH2-terminal actin-binding site. The possibility that the differences in MLC1F sequence among mammalian species, in and adjacent to the actin-binding region, are related to differences in modulation of cross-bridge kinetics in species with diverse locomotion kinetics is discussed.