bluuebunny/crossref_metadata_2025 huggingface dataset:
HADRON PHYSICS EXPERIMENTS IN ANTIPROTON–PROTON REACTIONS WITH THE PLANNED PANDA DETECTOR
Authors:   FOR THE PANDA COLLABORATION., HAWRANEK PIOTR
Published: February 2007

Fundamental questions concerning the strong interaction are addressed by the PANDA experiment at the future FAIR facility at GSI-Darmstadt. PANDA will be a general purpose detector of modular design optimized to measure the interaction of an antiproton beam with proton and heavy nuclear targets. The physics program at PANDA covers a wide range of topics including gluonic excitations, spectroscopy of strange and charm mesons, Drell-Yan and CP violating processes. This contribution focuses on the part of the physics program dealing with antiproton - proton annihilation.
SEARCH FOR η-NUCLEUS BOUND STATE AT COSY
Authors:   GEM COLLABORATION., Jha V. , Budzanowski A. , Chatterjee A. , Ernst J. , Hawranek P. , Kilian K. , Kliczewski S. , Kirillov Da. , Kirillov Di. , Kolev D. , Kravcikova M. , Kutsarova T. , Lesiak M. , Lieb J. , Machner H. , Magiera A. , Maier R. , Martinska G. , Nedev S. , Niskanen J. , Piskunov N. , Prasuhn D. , Protić D. , von Rossen P. , Roy B. J. , Shukla P. , Sitnik I. , Siudak R. , Tsenov R. , Ulicny M. , Urban J. , Vankova G.
Published: February 2007

An experiment to search for the bound state of η meson in nuclei has been performed at COSY, Juelich using the ENSTAR detector and Big Karl magnetic spectrometer. Reaction (p,3 He ) on 27 Al target has been used to search for the η-mesic nucleus 25 Mg η in the missing mass distribution from the measured 3 He particles. A preliminary figure of 1.5 nb for the upper limit of the formation cross section of η-nucleus bound state has been determined.
NUCLEAR ATTENUATION OF HADRONS AT HERMES
Authors:   FOR THE HERMES COLLABORATION., ELBAKIAN GAREGIN
Published: February 2007

The influence of the nuclear environment on the hadronization of charged pions, kaons and (anti)protons in semi-inclusive deep inelastic scattering has been studied by the HERMES experiment at DESY using a 27.5 GeV positron beam. Identified hadron multiplicities have been measured for helium, neon and krypton relative to thate of deuterium as a function of ν, z and [Formula: see text]. A large increase in the multiplicity ratios with [Formula: see text] was observed, clarifying the role of FSI in the nuclear transverse momentum broadening. In addition, double-hadron production in the nuclear medium was investigated. Nuclear effects on the double hadron-production ratio provided an additional tool for studying modifications of hadronization in nuclear matter.
DIELECTRIC FORMATION AND ELECTRICAL CHARACTERIZATION OF SINTERED TANTALUM SLUGS
Authors: GOVINDAIAH R. , BALAJI T. , KUMAR ARBIND , PARASURAM N. , PURUSHOTHAM Y. , SHARMA M. K. S. , PRAKASH T. L.
Published: February 2007

The present electronic industry requires capacitors having high capacitance with lower volume and space, high reliability and low leakage current. The solid tantalum capacitor ideally meets such requirements. In the present paper, the electrical characterization of tantalum anodes prepared from sodium reduced tantalum powder has been described. The capacitance, DC leakage current are measured for tantalum anodes made with different particle sizes of powders using the LCR Meter and DC Leakage Tester and compared with the physical and chemical properties. Interestingly, it was found that the DC leakage current decreases with decrease in particle size on contrary to the surface area. Besides, a trade-off appears imminent to establish the formation voltage and DC leakage current relationship.
A HIERARCHY OF DISCRETE INTEGRABLE SYSTEM AND ITS COUPLED ENLARGED INTEGRABLE SYSTEM
Authors: DING HAI-YONG , TIAN XIANG , XU XI-XIANG , YANG HONG-XIANG
Published: February 2007

A hierarchy of nonlinear integrable lattice soliton equations is derived from a discrete spectral problem. The hierarchy is proved to have discrete zero curvature representation. Using an enlarging algebra system [Formula: see text], we construct integrable couplings of the resulting hierarchy.
DIFFERENTIAL EQUATION APPROACH FOR ONE- AND TWO-DIMENSIONAL LATTICE GREEN'S FUNCTION
Authors: ASAD J. H.
Published: February 2007

A first-order differential equation of Green's function, at the origin G(0), for the one-dimensional lattice is derived by simple recurrence relation. Green's function at site (m) is then calculated in terms of G(0). A simple recurrence relation connecting the lattice Green's function at the site (m, n) and the first derivative of the lattice Green's function at the site (m ± 1, n) is presented for the two-dimensional lattice, a differential equation of second order in G(0, 0) is obtained. By making use of the latter recurrence relation, lattice Green's function at an arbitrary site is obtained in closed form. Finally, the phase shift and scattering cross-section are evaluated analytically and numerically for one- and two-impurities.
GENERALIZED MASTER EQUATION FOR NON-EXTENSIVE REACTION-DIFFUSION SYSTEMS
Authors: WU JUNLIN , CHEN HUAIJUN
Published: February 2007

Based on the theory of non-equilibrium statistics and density operator equation, the generalized master equation satisfied by characteristic function for the non-extensive reaction-diffusion systems affected by pressure is derived by calculating the time variation of probability distribution function, where the pressure of the non-extensive systems is given in the framework of Tsallis statistics. This new equation not only depends on the non-extensive parameter but also has more nonlinear terms as compared with the master equation in the phenomenological theory and thus has more generality.
NUMERICAL COMPARISON OF MULTI-PUMP RAMAN AMPLIFIERS BASED ON PHOTONIC CRYSTAL FIBER AND STANDARD SINGLE MODE FIBER
Authors: SHANG TAO , CHEN JIANPING , LI XINWAN , ZHOU JUNHE
Published: February 2007

This paper presents a numerical analysis and comparison on the performance of multi-pump gain-flat Raman amplifiers based on triangular photonic crystal fiber and conventional fiber. It is demonstrated that the extra 5.93 dB Raman net gain can be achieved in the L-band when PCF acts as Raman gain medium. The noise performance of the two amplifiers are also calculated and compared. Comparison with the data of published literature was also carried out to verify our analysis. The results showed that PCF is the appropriate candidate for high gain Raman amplifiers.
THE CONNECTION BETWEEN INTEGER QUANTUM HALL EFFECT AND FRACTIONAL QUANTUM HALL EFFECT
Authors: KOO JE HUAN , CHO GUANGSUP
Published: February 2007

We investigate the integer quantum Hall effect (IQHE) and the fractional quantum Hall effect (FQHE). We derive the quantized Hall resistance of IQHE in the presence of the high magnetic field using the scheme of standing waves by de Broglie matter wave of electron gas confined within a two-dimensional square-type quantum well. Without any modification of electrons and holes, it is shown that FQHE is only a decoupling mode of the Hall resistance by two-band-type of electrons and holes, which are governed by IQHE respectively.
CHAOS, FRACTALS AND QUANTUM POINCARÉ RECURRENCES IN DIAMAGNETIC KEPLER PROBLEM
Authors: UGULAVA A. , CHOTORLISHVILI L. , KERESELIDZE T. , SKRINNIKOV V.
Published: February 2007

The statistics of quantum Poincaré recurrences in Hilbert space for diamagnetic hydrogen atom in strong magnetic field has been investigated. It has been shown that quantities characterizing classical chaos are in good agreement with the ones that are used to describe quantum chaos. The equality of classical and quantum Poincaré recurrences has been shown. It has been proved that one of the signs of the emergence of quantum chaos is the irreversible transition from a pure quantum mechanical state to a mixed one.
WHICH POINT CONFIGURATIONS ARE DETERMINED BY THE DISTRIBUTION OF THEIR PAIRWISE DISTANCES?
Authors: BOUTIN MIREILLE , KEMPER GREGOR
Published: February 2007

In a previous paper we showed that, for any n ≥ m + 2, most sets of n points in ℝmare determined (up to rotations, reflections, translations and relabeling of the points) by the distribution of their pairwise distances. But there are some exceptional point configurations which are not reconstructible from the distribution of distances in the above sense. In this paper, we concentrate on the planar case m = 2 and present a reconstructibility test with running time O(n11). The cases of orientation preserving rigid motions (rotations and translations) and scalings are also discussed.
A FAST IMPLEMENTATION OF THE ISODATA CLUSTERING ALGORITHM
Authors: MEMARSADEGHI NARGESS , MOUNT DAVID M. , NETANYAHU NATHAN S. , LE MOIGNE JACQUELINE
Published: February 2007

Clustering is central to many image processing and remote sensing applications. ISODATA is one of the most popular and widely used clustering methods in geoscience applications, but it can run slowly, particularly with large data sets. We present a more efficient approach to ISODATA clustering, which achieves better running times by storing the points in a kd-tree and through a modification of the way in which the algorithm estimates the dispersion of each cluster. We also present an approximate version of the algorithm which allows the user to further improve the running time, at the expense of lower fidelity in computing the nearest cluster center to each point. We provide both theoretical and empirical justification that our modified approach produces clusterings that are very similar to those produced by the standard ISODATA approach. We also provide empirical studies on both synthetic data and remotely sensed Landsat and MODIS images that show that our approach has significantly lower running times.
SOLVING INCREMENTAL SATISFIABILITY
Authors: MOUHOUB MALEK , SADAOUI SAMIRA
Published: February 2007

Propositional satisfiability (SAT) problem is fundamental to the theory of NP-completeness. Indeed, using the concept of "polynomial-time reducibility" all NP-complete problems can be polynomially reduced to SAT. Thus, any new technique for satisfiability problems will lead to general approaches for thousands of hard combinatorial problems. In this paper, we introduce the incremental propositional satisfiability problem that consists of maintaining the satisfiability of a propositional formula anytime a conjunction of new clauses is added. More precisely, the goal here is to check whether a solution to a SAT problem continues to be a solution anytime a new set of clauses is added and if not, whether the solution can be modified efficiently to satisfy the old formula and the new clauses. We will study the applicability of systematic and approximation methods for solving incremental SAT problems. The systematic method is based on the branch and bound technique while the approximation methods rely on stochastic local search and genetic algorithms. Experimental tests, conducted on randomly generated SAT instances, demonstrate the efficiency in time of the approximation methods over the branch and bound algorithm. However these approximation methods do not always guarantee the completeness of the solution returned. We show that a method we propose that uses non systematic search in a limited form together with branch and bound has the best compromise, in practice, between time and quality of the solution returned (success ratio).
AMPHICHEIRAL KNOTS WITH EVERY EVEN CROSSING NUMBER
Authors: DAR APARNA
Published: February 2007

The goal of this note is to give an affirmative answer to Problem 1.66B of Kirby's problem list [2]: "Are there prime alternating amphicheiral knots with every possible even crossing number?".
FRETTING WEAR BEHAVIOR OF TIN PLATED CONTACTS: INFLUENCE ON CONTACT RESISTANCE
Authors: PARK YOUNG WOO , SANKARA NARAYANAN T. S. N. , LEE KANG YONG
Published: February 2007

The fretting wear behavior of tin plated copper alloy contacts and its influence on the contact resistance are addressed in this paper. Based on the change in the area of contact zone as well as the wear depth as a function of fretting cycles, a model was proposed to explain the observed low and stable contact resistance. The extent of wear of tin coating and the formation of wear debris as a function of fretting cycles were assessed by scanning electron microscopy (SEM). Energy dispersive X-ray line scanning (EDX), X-ray mapping, and EDX spot analysis were employed to characterize the nature of changes that occur at the contact zone. The study reveals that the fretted area increases linearly up to 8000 cycles due to the continuous removal of the tin coating and attains saturation when the fretting path length reaches a maximum. The observed low and stable contact resistance observed up to 8000 cycles is due to the common area of contact which provides an electrically conducting area. Surface analysis by SEM, EDX, and X-ray elemental mapping elucidate the nature of changes that occurred at the contact zone. Based on the change in contact resistance as a function of fretting cycles, the fretting wear and fretting corrosion dominant regimes are proposed. The interdependence of extent of wear and oxidation increases the complexity of the fretting corrosion behavior of tin plated contacts.
KNOWLEDGE-DRIVEN INTERACTIONS ACROSS MOBILE AD HOC NETWORKS
Authors: SEN ROHAN , HANDOREAN RADU , ROMAN GRUIA-CATALIN , HACKMANN GREGORY , GILL CHRISTOPHER
Published: February 2007

The decoupled nature of computing in mobile ad hoc networks (MANETs) can result in disconnections at inopportune times during an interaction between a pair of hosts. We introduce the notion of a priori selection of partner hosts to reduce the likelihood of disconnection during such interactions. An application may specify the times when and the physical locations where it requires interactions with peer applications on partner hosts. A knowledge base of the physical motion profiles of various hosts maintained on each mobile host is used to select partner hosts that are co-located with the reference host at the required time and are least likely to disconnect. In this paper, we present a formal model for such knowledge management, along with an algorithm used to determine suitable partner hosts. We also provide details of our implementation of partner selection, which has been used in the context of a service-oriented computing middleware for MANETs, developed previously by our group. Finally, we present simulation results of our approach.
INTUITIONISTIC FUZZY K-PROXIMITY SPACES
Authors: KANDIL A. , TANTAWY O. , BARAKAT K.
Published: February 2007

We shall extend the notion of a K-proximity relation and its properties into an intuitionistic fuzzy sense. We generate an intuitionistic fuzzy K-proximity by a given fuzzy K-proximity in different forms. Also, intuitionistic fuzzy K-proximity mappings and its properties are considered.
A TWO LAYER SUPPLY-DEMAND ANALYSIS MODEL FOR EVALUATING TOURISM ONLINE SERVICE
Authors: LU ZI , HAN BING , LI YANLI , DENG ZHUOPENG , ZHANG ZUI
Published: February 2007

In order to help tourism organizations enhance customer satisfaction (CS) for their websites and online services, this study develops a two layer supply-demand analysis model for tourism websites CS evaluation. This model is built based on the functionalities of tourism websites, and it mainly focuses on the CS evaluations from successful tourism websites applications. A number of tourism online service websites in Beijing, China, are taken as study cases for measuring and analyzing the supply-demand difference of online services presented in the model. The model can be used in regional tourism management to identify issues regarding the activity characteristics of tourism websites and to obtain suggestions to both customer satisfaction and tourism website provider profit.
The Biology of Arabinogalactan Proteins
Authors: Seifert Georg J. , Roberts Keith
Published: February 2007

Arabinogalactan proteins is an umbrella term applied to a highly diverse class of cell surface glycoproteins, many of which contain glycosylphosphatidylinositol lipid anchors. The structures of protein and glycan moieties of arabinogalactan proteins are overwhelmingly diverse while the “hydroxproline contiguity hypothesis” predicts arabinogalactan modification of members of many families of extracellular proteins. Descriptive studies using monoclonal antibodies reacting with carbohydrate epitopes on arabinogalactan proteins and experimental work using β-Yariv reagent implicate arabinogalactan proteins in many biological processes of cell proliferation and survival, pattern formation and growth, and in plant microbe interaction. Advanced structural understanding of arabinogalactan proteins and an emerging molecular genetic definition of biological roles of individual arabinogalactan protein species, in conjunction with potentially analogous extracellular matrix components of animals, stimulate hypotheses about their mode of action. Arabinogalactan proteins might be soluble signals, or might act as modulators and coreceptors of apoplastic morphogens; their amphiphilic molecular nature makes them prime candidates of mediators between the cell wall, the plasma membrane, and the cytoplasm.
Physiological Roles of G Protein–Coupled Receptor Kinases and Arrestins
Authors: Premont Richard T. , Gainetdinov Raul R.
Published: February 2007

Heterotrimeric G protein–coupled receptors (GPCRs) are found on the surface of all cells of multicellular organisms and are major mediators of intercellular communication. More than 800 distinct GPCRs are present in the human genome, and individual receptor subtypes respond to hormones, neurotransmitters, chemokines, odorants, or tastants. GPCRs represent the most widely targeted pharmacological protein class. Because drugs that target GPCRs often engage receptor regulatory mechanisms that limit drug effectiveness, particularly in chronic treatment, there is great interest in understanding how GPCRs are regulated, as a basis for designing therapeutic drugs that evade this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein–coupled receptor kinases (GRKs), followed by binding of arrestin proteins, which prevent receptors from activating downstream heterotrimeric G protein pathways while allowing activation of arrestin-dependent signaling pathways. Although the general mechanisms of GRK-arrestin regulation have been well explored in model cell systems and with purified proteins, much less is known about the role of GRK-arrestin regulation of receptors in physiological and pathophysiological settings. This review focuses on the physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders as well as on recent studies using knockout and transgenic mice to explore the role of GRK-arrestin regulation of GPCRs in vivo.
Behavioral characterization and modulation of circadian rhythms by light and melatonin in C3H/HeN mice homozygous for the RORβ knockout
Authors: Masana Monica I. , Sumaya Isabel C. , Becker-Andre Michael , Dubocovich Margarita L.
Published: February 2007

This study reports for the first time the effects of retinoid-related orphan receptors [RORβ; receptor gene deletion RORβ(C3H)−/−] in C3H/HeN mice on behavioral and circadian phenotypes. Pineal melatonin levels showed a robust diurnal rhythm with high levels at night in wild-type (+/+), heterozygous (+/−), and knockout (−/−) mice. The RORβ(C3H)−/−mice displayed motor (“duck gait,” hind paw clasping reflex) and olfactory deficits, and reduced anxiety and learned helplessness-related behaviors. Circadian rhythms of wheel-running activity in all genotypes showed entrainment to the light-dark (LD) cycle, and free running in constant dark, with RORβ(C3H)−/−mice showing a significant increase in circadian period ( tau). Melatonin administration (90 μg/mouse sc for 3 days) at circadian time (CT) 10 induced phase advances, while exposure to a light pulse (300 lux) at CT 14 induced phase delays of circadian activity rhythms of the same magnitude in all genotypes. In RORβ(C3H)−/−mice a light pulse at CT 22 elicited a larger phase advance in activity rhythms and a slower rate of reentrainment after a 6-h advance in the LD cycle compared with (+/+) mice. Yet, the rate of reentrainment was significantly advanced by melatonin administration at the new dark onset in both (+/+) and (−/−) mice. We conclude that the RORβ nuclear receptor is not involved in either the rhythmic production of pineal melatonin or in mediating phase shifts of circadian rhythms by melatonin, but it may regulate clock responses to photic stimuli at certain time domains.
Effects of 20-HETE on Na+transport and Na+-K+-ATPase activity in the thick ascending loop of Henle
Authors: Yu Ming , Lopez Bernardo , Dos Santos Elisabete A. , Falck John R. , Roman Richard J.
Published: February 2007

Previous studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) inhibits Na+transport in the medullary thick ascending loop of Henle (mTALH), but the mechanisms involved remain uncertain. The present study compared the effects of 20-HETE with those of ouabain and furosemide on intracellular Na+concentration ([Na+]i), Na+-K+-ATPase activity, and86Rb+uptake, an index of Na+transport, in mTALH isolated from rats. Ouabain (2 mM) increased, whereas furosemide (100 μM) decreased, [Na+]iin the mTALH of rats. Ouabain and furosemide inhibited86Rb+uptake by 91 and 30%, respectively. 20-HETE (1 μM) had a similar effect as ouabain and increased [Na+]ifrom 19 ± 1 to 30 ± 1 mM. 20-HETE reduced Na+-K+-ATPase activity by 30% and86Rb+uptake by 37%, but it had no effect on86Rb+uptake or [Na+]iin the mTALH of rats pretreated with ouabain. 20-HETE inhibited86Rb+uptake by 12% and increased [Na+]iby 19 mM in mTALH pretreated with furosemide. These findings indicate that 20-HETE secondarily inhibits Na+transport in the mTALH of the rat, at least, in part by inhibiting the Na+-K+-ATPase activity and raising [Na+]i.
Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease
Authors: McNulty Patrick H. , Robertson Bryan J. , Tulli Mark A. , Hess Joshua , Harach Lisa A. , Scott Sofia , Sinoway Lawrence I.
Published: February 2007

Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease (IHD) by interfering with physiological regulation of coronary tone. To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting, we measured the effect of an acute oxidative stress (breathing 100% oxygen) on coronary capacitance artery diameter (quantitative angiography) and blood flow velocity through the coronary microcirculation (intracoronary Doppler ultrasonography) before and after treatment with the antioxidant vitamin C (3-g intravenous infusion) in 12 IHD patients undergoing a clinical coronary interventional procedure. Relative to room air breathing, 100% oxygen breathing promptly reduced coronary blood flow velocity by 20% and increased coronary resistance by 23%, without significantly changing the diameter of capacitance arteries. Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level, and it prevented the reinduction of coronary constriction with rechallenge with 100% oxygen. This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD, and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation. This observation may have relevance for clinical practice.
Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction
Authors: Starnes Joseph W. , Barnes Brian D. , Olsen Marissa E.
Published: February 2007

Exercise provides cardioprotection against ischemia-reperfusion injury, a process involving mitochondrial reactive oxygen species (ROS) generation and calcium overload. This study tested the hypotheses that isolated mitochondria from hearts of endurance-trained rats have decreased ROS production and improved tolerance against Ca2+-induced dysfunction. Male Fischer 344 rats were either sedentary (Sed, n = 8) or endurance exercise trained (ET, n = 11) by running on a treadmill for 16 wk (5 days/wk, 60 min/day, 25 m/min, 6° grade). Mitochondrial oxidative phosphorylation measures were determined with glutamate-malate or succinate as substrates, and H2O2production and permeability transition pore (PTP) opening were determined with succinate. All assays were carried out in the absence and presence of calcium. In response to 25 and 50 μM CaCl2, Sed and ET displayed similar decreases in state 3 respiration, respiratory control ratio, and ADP:O ratio. Ca2+-induced PTP opening was also similar. However, H2O2production by ET was lower than Sed ( P < 0.05) in the absence of calcium (323 ± 12 vs. 362 ± 11 pmol·min−1·mg protein−1) and the presence of 50 μM CaCl2(154 ± 3 vs. 197 ± 7 pmol·min−1·mg protein−1). Rotenone, which blocks electron flow from succinate to complex 1, reduced H2O2production and eliminated differences between ET and Sed. Mitochondrial superoxide dismutase and glutathione peroxidase were not affected by exercise. Catalase activity was extremely low but increased 49% in ET ( P < 0.05). In conclusion, exercise reduces ROS production in myocardial mitochondria through adaptations specific to complex 1 but does not improve mitochondrial tolerance to calcium overload.
Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis
Authors: Baker Emma H. , Clark Nicholas , Brennan Amanda L. , Fisher Donald A. , Gyi Khin M. , Hodson Margaret E. , Philips Barbara J. , Baines Deborah L. , Wood David M.
Published: February 2007

In animals, glucose concentrations are 3–20 times lower in lung lining fluid than in plasma. In humans, glucose concentrations are normally low (<1 mmol/l) in nasal and bronchial fluid, but they are elevated by inflammation or hyperglycemia. Furthermore, elevated bronchial glucose is associated with increased respiratory infection in intensive care patients. Our aims were to estimate normal glucose concentrations in fluid from distal human lung sampled noninvasively and to determine effects of hyperglycemia and lung disease on lung glucose concentrations. Respiratory fluid was sampled as exhaled breath condensate, and glucose was measured by chromatography with pulsed amperometric detection. Dilution corrections, based on conductivity, were applied to estimate respiratory fluid glucose concentrations (breath glucose). We found that breath glucose in healthy volunteers was 0.40 mmol/l (SD 0.24), reproducible, and unaffected by changes in salivary glucose. Breath-to-blood glucose ratio (BBGR) was 0.08 (SD 0.05). Breath glucose increased during experimental hyperglycemia ( P < 0.05) and was elevated in diabetic patients without lung disease [1.20 mmol/l (SD 0.69)] in proportion to hyperglycemia [BBGR 0.09 (SD 0.06)]. Breath glucose was elevated more than expected for blood glucose in cystic fibrosis patients [breath 2.04 mmol/l (SD 1.14), BBGR 0.29 (SD 0.17)] and in cystic fibrosis-related diabetes [breath 4.00 mmol/l (SD 2.07), BBGR 0.54 (0.28); P < 0.0001]. These data indicate that 1) this method makes a biologically plausible estimate of respiratory fluid glucose concentration, 2) respiratory fluid glucose concentrations are elevated by hyperglycemia and lung disease, and 3) effects of hyperglycemia and lung disease can be distinguished using the BBGR. This method will support future in vivo investigation of the cause and effect of elevated respiratory fluid glucose in human lung disease.
Regulation of the Crab Heartbeat by Crustacean Cardioactive Peptide (CCAP): Central and Peripheral Actions
Authors: Fort Timothy J. , García-Crescioni Keyla , Agricola Hans-Jürgen , Brezina Vladimir , Miller Mark W.
Published: February 2007

In regulating neurophysiological systems, neuromodulators exert multiple actions at multiple sites in such a way as to control the activity in an integrated manner. We are studying how this happens in a simple central pattern generator (CPG)–effector system, the heart of the blue crab Callinectes sapidus. The rhythmic contractions of this heart are neurogenic, driven by rhythmic motor patterns generated by the cardiac ganglion (CG). In this study, we used anatomical and physiological methods to examine the sources and actions on the system of crustacean cardioactive peptide (CCAP). Immunohistochemical localization revealed a plexus of CCAP-immunoreactive fibers in the pericardial organs (POs), neurohemal structures from which blood-borne neurohormones reach the heart. Combined backfill and immunohistochemical experiments indicated that the CCAP in the POs originated from a large contralateral neuron in each thoracic neuromere. In physiological experiments, we examined the actions of exogenous CCAP on the intact working heart, on the semi-intact heart in which we could record the motor patterns as well as the muscle contractions, and on the isolated CG. CCAP had strong positive inotropic and chronotropic effects. Dissection of these effects in terms of dose dependency, time course, and the preparation type in which they occurred suggested that they were produced by the interaction of three primary actions of CCAP exerted both on the heart muscle and on the CG. We conclude that CCAP released from the POs as a neurohormone regulates the crab heart by multiple actions on both the central and peripheral components of this model CPG–effector system.
Neural Coding of Reward-Prediction Error Signals During Classical Conditioning With Attractive Faces
Authors: Bray Signe , O'Doherty John
Published: February 2007

Attractive faces can be considered to be a form of visual reward. Previous imaging studies have reported activity in reward structures including orbitofrontal cortex and nucleus accumbens during presentation of attractive faces. Given that these stimuli appear to act as rewards, we set out to explore whether it was possible to establish conditioning in human subjects by pairing presentation of arbitrary affectively neutral stimuli with subsequent presentation of attractive and unattractive faces. Furthermore, we scanned human subjects with functional magnetic resonance imaging (fMRI) while they underwent this conditioning procedure to determine whether a reward-prediction error signal is engaged during learning with attractive faces as is known to be the case for learning with other types of reward such as juice and money. Subjects showed changes in behavioral ratings to the conditioned stimuli (CS) when comparing post- to preconditioning evaluations, notably for those CSs paired with attractive female faces. We used a simple Rescorla-Wagner learning model to generate a reward-prediction error signal and entered this into a regression analysis with the fMRI data. We found significant prediction error-related activity in the ventral striatum during conditioning with attractive compared with unattractive faces. These findings suggest that an arbitrary stimulus can acquire conditioned value by being paired with pleasant visual stimuli just as with other types of reward such as money or juice. This learning process elicits a reward-prediction error signal in a main target structure of dopamine neurons: the ventral striatum. The findings we describe here may provide insights into the neural mechanisms tapped into by advertisers seeking to influence behavioral preferences by repeatedly exposing consumers to simple associations between products and rewarding visual stimuli such as pretty faces.
Mice Lacking bi-1 Gene Show Accelerated Liver Regeneration
Authors: Bailly-Maitre Béatrice , Bard-Chapeau Emilie , Luciano Fréderic , Droin Nathalie , Bruey Jean-Marie , Faustin Benjamin , Kress Christina , Zapata Juan M. , Reed John C.
Published: February 2007

The liver has enormous regenerative capacity such that, after partial hepatectomy, hepatocytes rapidly replicate to restore liver mass, thus providing a context for studying in vivo mechanisms of cell growth regulation. Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death. Interestingly, the BI-1 protein has been shown to regulate Ca2+ handling by the ER similar to antiapoptotic Bcl-2 family proteins. Effects on cell cycle entry by Bcl-2 family proteins have been described, prompting us to explore whether bi-1–deficient mice display alterations in the in vivo regulation of cell cycle entry using a model of liver regeneration. Accordingly, we compared bi-1+/+ and bi-1−/− mice subjected to partial hepatectomy with respect to the kinetics of liver regeneration and molecular events associated with hepatocyte proliferation. We found that bi-1 deficiency accelerates liver regeneration after partial hepatectomy. Regenerating hepatocytes in bi-1−/− mice enter cell cycle faster, as documented by more rapid incorporation of deoxynucleotides, associated with earlier increases in cyclin D1, cyclin D3, cyclin-dependent kinase (Cdk) 2, and Cdk4 protein levels, more rapid hyperphosphorylation of retinoblastoma protein, and faster degradation of p27Kip1. Dephosphorylation and nuclear translocation of nuclear factor of activated T cells 1 (NFAT1), a substrate of the Ca2+-sensitive phosphatase calcineurin, were also accelerated following partial hepatectomy in BI-1–deficient hepatocytes. These findings therefore reveal additional similarities between BI-1 and Bcl-2 family proteins, showing a role for BI-1 in regulating cell proliferation in vivo, in addition to its previously described actions as a regulator of cell survival. [Cancer Res 2007;67(4):1442–50]
Gefitinib Reverses TRAIL Resistance in Human Bladder Cancer Cell Lines via Inhibition of AKT-Mediated X-Linked Inhibitor of Apoptosis Protein Expression
Authors: Shrader Marissa , Pino Maria Simona , Lashinger Laura , Bar-Eli Menashe , Adam Liana , Dinney Colin P.N. , McConkey David J.
Published: February 2007

In a previous study, we found that the small-molecule epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa) blocked cell proliferation at biologically relevant concentrations in approximately one third (6 of 17) of human bladder cancer cell lines examined. Here, we studied the effects of gefitinib on apoptosis in a representative subset of the same panel of cells. The drug had modest effects on DNA fragmentation as a single agent at concentrations that produced strong growth inhibition (≤1 μmol/L) and also failed to promote apoptosis induced by conventional chemotherapeutic agents (gemcitabine and paclitaxel). However, gefitinib did interact with recombinant human tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) to induce high levels of apoptosis in gefitinib-responsive but not gefitinib-unresponsive lines. The molecular mechanisms involved down-regulation of active AKT and X-linked inhibitor of apoptosis protein (XIAP) expression and were mimicked by chemical inhibitors of the phosphatidylinositol 3-kinase/AKT pathway but not of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase/ERK pathway. Furthermore, direct small interfering RNA–mediated knockdown of AKT resulted in down-regulation of XIAP and TRAIL sensitization, and knockdown of XIAP itself was sufficient to reverse TRAIL resistance. Together, our results show that EGFR pathway activation limits TRAIL-induced apoptosis via an AKT- and XIAP-dependent mechanism in EGFR-dependent human bladder cancer cells, providing the conceptual framework for a further evaluation of the combination in relevant preclinical in vivo models. [Cancer Res 2007;67(4):1430–5]
PEA-15 Inhibits Tumor Cell Invasion by Binding to Extracellular Signal-Regulated Kinase 1/2
Authors: Glading Angela , Koziol James A. , Krueger Joseph , Ginsberg Mark H.
Published: February 2007

Phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) binds to extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinases to alter ERK1/2 cellular localization and target preferences and binds to adaptors in the extrinsic cell death pathway to block apoptosis. Here, we report that PEA-15 protein expression is inversely correlated with the invasive behavior of breast cancer in an immunohistochemical analysis of a breast cancer progression tissue microarray. Short hairpin RNA–mediated inhibition of PEA-15 expression increased the invasion of PEA-15–expressing tumor cells in vitro, suggesting a causative role for PEA-15 in the inhibition of invasion. This causative role was confirmed by the finding that the enforced expression of PEA-15 in invasive tumor cells reduced invasion. The effect of PEA-15 on tumor invasion is mediated by its interaction with ERK1/2 as shown by the following: (a) PEA-15 mutants that fail to bind ERK1/2 did not inhibit invasion; (b) overexpression of ERK1 or activated MAP/ERK kinase (MEK) reversed the inhibitory effect of PEA-15; (c) when an inhibitor of ERK1/2 activation reduced invasion, PEA-15 expression did not significantly reduce invasion further. Furthermore, we find that the effect of PEA-15 on invasion seems to relate to the nuclear localization of activated ERK1/2. PEA-15 inhibits invasion by keeping ERK out of the nucleus, as a PEA-15 mutant that cannot prevent ERK nuclear localization was not able to inhibit invasion. In addition, membrane-localized ERK1, which sequesters endogenous ERK1 to prevent its nuclear localization, also inhibited invasion. These results reveal that PEA-15 regulates cancer cell invasion via its ability to bind ERK1/2 and indicate that nuclear entry of ERK1/2 is important in tumor behavior. [Cancer Res 2007;67(4):1536–44]
Smad4 Regulates Claudin-1 Expression in a Transforming Growth Factor-β–Independent Manner in Colon Cancer Cells
Authors: Shiou Sheng-Ru , Singh Amar B. , Moorthy Krishnan , Datta Pran K. , Washington M. Kay , Beauchamp R. Daniel , Dhawan Punita
Published: February 2007

We have recently reported that the expression of a tight junction protein, claudin-1, is increased during colon carcinogenesis and particularly metastatic colorectal cancer. Manipulation of claudin-1 levels in colon cancer cells showed a positive correlation between claudin-1 expression and tumor growth and metastasis. However, the mechanisms underlying the increased claudin-1 expression in colorectal cancer remains unknown. The tumor suppressor Smad4 is a central intracellular signal transduction component of the transforming growth factor-β (TGF-β) family of cytokines. Loss of Smad4 protein expression is correlated with poor prognosis and is frequently observed in invasive and metastatic colorectal carcinoma. In the present study, we report an inverse relationship between Smad4 and claudin-1 expression in human colorectal carcinoma tumor samples and in human colon cancer cell lines. We found that the expression of Smad4 in Smad4-deficient but claudin-1–positive SW480 or HT29 colon cancer cell lines down-regulates claudin-1 expression through transcriptional repression by modulating β-catenin/T-cell factor/lymphocyte enhancer factor activity. Furthermore, this Smad4-dependent inhibition of claudin-1 expression is independent of TGF-β signaling because Smad4 expression alone is insufficient to restore TGF-β signaling in the SW480 cells, and the selective TGF-β receptor kinase inhibitor LY364947 did not prevent the Smad4 suppression of claudin-1 protein expression in either SW480 or HT29 cells. Taken together, these findings suggest a novel mechanism underlying Smad4 tumor–suppressive function through regulation of a potential metastatic modulator, claudin-1, in a TGF-β–independent manner. [Cancer Res 2007;67(4):1571–9]
An Emerging Role for Endothelial Nitric Oxide Synthase in Chronic Inflammation and Cancer
Authors: Ying Lei , Hofseth Lorne J.
Published: February 2007

Nitric oxide (NO) is a free radical that is involved in carcinogenesis. Recent literature indicates that endothelial NO synthase (eNOS) can modulate cancer-related events (angiogenesis, apoptosis, cell cycle, invasion, and metastasis). We review the literature linking eNOS to carcinogenesis to encourage future research assessing the role of eNOS in cancer prevention and treatment. [Cancer Res 2007;67(4):1407–10]
Possible Role of Semaphorin 3F, a Candidate Tumor Suppressor Gene at 3p21.3, in p53-Regulated Tumor Angiogenesis Suppression
Authors: Futamura Manabu , Kamino Hiroki , Miyamoto Yuji , Kitamura Noriaki , Nakamura Yasuyuki , Ohnishi Shiho , Masuda Yoshiko , Arakawa Hirofumi
Published: February 2007

Although the regulation of tumor angiogenesis is believed to be one of the core functions of p53, the mechanism still remains to be elucidated. Here, we report that semaphorin 3F (SEMA3F), an axon guidance molecule, is involved in p53-regulated antiangiogenesis. The expression level of SEMA3F mRNA was increased by both exogenous and endogenous p53. Chromatin immunoprecipitation assay indicated that a potent p53-binding sequence in intron 1 of SEMA3F interacts with p53 and that it has a p53-responsive transcriptional activity. Overexpression of SEMA3F inhibited in vitro cell growth of the lung cancer cell line H1299. In nude mice assay, the size of the H1299 tumors expressing SEMA3F was much smaller, and they showed lesser number of blood vessels as compared with the control tumors. Moreover, tumors derived from the p53-knockdown colorectal cancer cell line LS174T displayed a remarkable enhancement of tumor vessel formation as compared with control tumors containing normal levels of p53. The expression levels of SEMA3F and neuropilin-2 (NRP2), the functional receptor for SEMA3F, in p53-knockdown LS174T tumors were lower than those in the control tumors. Adenovirus-mediated SEMA3F gene transfer induced the remarkable in vitro growth suppression of the stable transformant of H1299 cells, which express high levels of NRP2. These results suggest that p53 negatively regulates tumor vessel formation and cell growth via the SEMA3F-NRP2 pathway. [Cancer Res 2007;67(4):1451–9]
Thrombospondin-1 Peptide ABT-510 Combined with Valproic Acid Is an Effective Antiangiogenesis Strategy in Neuroblastoma
Authors: Yang Qiwei , Tian Yufeng , Liu Shuqing , Zeine Rana , Chlenski Alexandre , Salwen Helen R. , Henkin Jack , Cohn Susan L.
Published: February 2007

In the pediatric cancer neuroblastoma, clinically aggressive disease is associated with increased levels of angiogenesis stimulators and high vascular index. We and others have hypothesized that blocking angiogenesis may be effective treatment for this pediatric malignancy. However, little is known about the efficacy of antiangiogenic agents in pediatric malignancies. Recently, promising results have been reported in an adult phase I study of ABT-510, a peptide derivative of the natural angiogenic inhibitor thrombospondin-1. Histone deacetylase inhibitors, such as valproic acid (VPA), have also been shown to have antiangiogenic activity in several cancer models. In this study, we evaluated the effects of ABT-510 and VPA on neuroblastoma tumor growth and angiogenesis. Although only VPA was capable of blocking the proliferation of neuroblastoma cells and inducing neuroblastoma cell apoptosis in vitro, treatment with VPA or ABT-510 alone significantly suppressed the growth of neuroblastoma xenografts established from two different MYCN-amplified cell lines. Combination therapy more effectively inhibited the growth of small neuroblastoma xenografts than single-agent treatment, and in animals with large xenografts, total cessation of tumor growth was achieved with this treatment approach. The microvascular density was significantly reduced in the xenografts treated with combination therapy compared with controls or tumors treated with single agents. In addition, the number of structurally abnormal vessels was reduced, suggesting that these agents may “normalize” the tumor vasculature. Our results indicate that ABT-510 combined with VPA may be an effective antiangiogenic treatment strategy for children with high-risk neuroblastoma. [Cancer Res 2007;67(4):1716–24]
Endothelin-1 and Endothelin-3 Promote Invasive Behavior via Hypoxia-Inducible Factor-1α in Human Melanoma Cells
Authors: Spinella Francesca , Rosanò Laura , Di Castro Valeriana , Decandia Samantha , Nicotra Maria Rita , Natali Pier Giorgio , Bagnato Anna
Published: February 2007

Endothelin (ET) B receptor (ETBR), which is overexpressed in human cutaneous melanomas, promotes tumorigenesis upon activation by ET-1 or ET-3, thus representing a potential novel therapeutic target. Hypoxia-inducible factor-1α (HIF-1α) is the transcriptional factor that conveys signaling elicited by hypoxia and growth factor receptors. Here, we investigated the interplay between ET axis and hypoxia in primary and metastatic melanoma cell lines. We report that under normoxic conditions, ETBR activation by ET-1/ET-3 enhances vascular endothelial growth factor (VEGF) up-regulation, cyclooxygenase (COX)-1/COX-2 protein expression and COX-2 promoter activity, prostaglandin E2 (PGE2) production, and do so to a greater extent under hypoxia. Moreover, COX-1/COX-2 inhibitors block ET-induced PGE2 and VEGF secretion, matrix metalloproteinase (MMP) activation, and cell invasion, indicating that both enzymes function as downstream mediators of ET-induced invasive properties. The ETBR selective antagonist BQ788 or transfection with ETBR small interfering RNA (siRNA) block the ET-mediated effects. ETs also increase HIF-1α expression under both normoxic and hypoxic conditions and its silencing by siRNA desensitizes COX-2 transcriptional activity, PGE2 and VEGF production, and MMP activation in response to ET-3, implicating, for the first time, HIF-1α/COX as downstream targets of ETBR signaling leading to invasiveness. In melanoma xenografts, specific ETBR antagonist suppresses tumor growth, neovascularization, and invasiveness-related factors. Collectively, these results identify a new mechanism whereby ET-1/ET-3/ETBR axis can promote and interact with the HIF-1α–dependent machinery to amplify the COX-mediated invasive behavior of melanoma. New therapeutic strategies using specific ETBR antagonist could provide an improved approach to the treatment of melanoma by inhibiting tumor growth and progression. [Cancer Res 2007;67(4):1725–34]
TSC1 Sets the Rate of Ribosome Export and Protein Synthesis through Nucleophosmin Translation
Authors: Pelletier Corey L. , Maggi Leonard B. , Brady Suzanne N. , Scheidenhelm Danielle K. , Gutmann David H. , Weber Jason D.
Published: February 2007

Nucleophosmin (B23) is a nucleolar phosphoprotein that has been implicated in numerous cellular processes. In particular, nucleophosmin interacts with nucleolar components of newly synthesized ribosomes to promote ribosome nuclear export. Nucleophosmin is a classic mitogen-induced protein, with changes in its expression correlating with growth factor stimulation. In this study, we examined the underlying mechanism of nucleophosmin induction and showed that hyperproliferative signals emanating from oncogenic H-RasV12 cause tremendous increases in nucleophosmin protein expression. Nucleophosmin protein accumulation was dependent on mammalian target of rapamycin (mTOR) activation, as rapamycin completely prevented nucleophosmin induction. Consistent with this finding, genetic ablation of Tsc1, a major upstream inhibitor of mTOR, resulted in nucleophosmin protein induction through increased translation of existing nucleophosmin mRNAs. Increases in nucleophosmin protein accumulation were suppressed by reintroduction of TSC1. Induction of nucleophosmin through Tsc1 loss resulted in a greater pool of actively translating ribosomes in the cytoplasm, higher overall rates of protein synthesis, and increased cell proliferation, all of which were dependent on efficient nucleophosmin nuclear export. Nucleophosmin protein accumulation in the absence of Tsc1 promoted the nuclear export of maturing ribosome subunits, providing a mechanistic link between TSC1/mTOR signaling, nucleophosmin-mediated nuclear export of ribosome subunits, protein synthesis levels, and cell growth. [Cancer Res 2007;67(4):1609–17]