bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Quaternary Atmospheric CH
4
Isotope Record Suggests Marine Clathrates Are Stable
Authors: Sowers Todd
Published: February 2006

One explanation for the abrupt increases in atmospheric CH
4
, that occurred repeatedly during the last glacial cycle involves clathrate destabalization events. Because marine clathrates have a distinct deuterium/hydrogen (D/H) isotope ratio, any such destabilization event should cause the D/H ratio of atmospheric CH
4
(δD
CH4
) to increase. Analyses of air trapped in the ice from the second Greenland ice sheet project show stable and/or decreasing δD
CH4
values during the end of the Younger and Older Dryas periods and one stadial period, suggesting that marine clathrates were stable during these abrupt warming episodes. Elevated glacial δD
CH4
values may be the result of a lower ratio of net to gross wetland CH
4
emissions and an increase in petroleum-based emissions.
Reductive Cyclotrimerization of Carbon Monoxide to the Deltate Dianion by an Organometallic Uranium Complex
Authors: Summerscales Owen T. , Cloke F. Geoffrey N. , Hitchcock Peter B. , Green Jennifer C. , Hazari Nilay
Published: February 2006

Despite the long history of the Fischer-Tropsch reaction, carbon monoxide has proven remarkably resistant to selective homologation under mild conditions. Here, we find that an organouranium(III) complex induces efficient reductive trimerization of carbon monoxide at room temperature and pressure. The result is a triangular, cyclic C
3
O
2–
3
, or deltate, dianion held between two uranium(IV) units. The bonding within the C
3
O
2–
3
unit and its coordination to the two U centers have been analyzed by x-ray diffraction and density functional theory computational studies, which show a stabilizing C-C agostic interaction between the C
3
core and one U center. Solution nuclear magnetic resonance studies reveal a rapid equilibration of the deltate unit between the U centers.
Wallowing in the Wastebin
Authors: Allchin Douglas
Published: February 2006

Theories on the Scrap Heap
. Scientists and Philosophers on the Falsification, Rejection, and Replacement of Theories.
By John Losee
. University of Pittsburgh Press, Pittsburgh, PA, 2005. 216 pp. $24.95. ISBN 0-8229- 5873-2.

Using excerpts from the writings of researchers and philosophers, the author considers questions about the falsification, rejection, and replacement of scientific theories.
Chicken Monster or Chicken Little?
Authors: Wolinsky Steven M.
Published: February 2006

The Monster at Our Door
. The Global Threat of Avian Flu.
By Mike Davis
. New Press, New York, 2005. 220 pp. $21.95, C$26.95, €12.99. ISBN 1-59558-011-5.

The author summarizes the evolution of H5N1 and related viruses and discusses factors---burgeoning slums, agribusiness, fast-food industries, corrupt governments---that have created conditions conducive to the emergence of a pandemic.
CELL/SYMBOL COMPLEXITY OF TISSUE P SYSTEMS WITH SYMPORT/ANTIPORT RULES
Authors: ALHAZOV ARTIOM , FREUND RUDOLF , OSWALD MARION
Published: February 2006

We consider tissue P systems with symport/antiport rules and investigate their computational power when using only a (very) small number of symbols and cells. Even when using only one symbol, we need at most six (seven when allowing only one channel between a cell and the environment) cells to generate any recursively enumerable set of natural numbers. On the other hand, with only one cell we can only generate regular sets when using one channel with the environment, whereas one cell with two channels between the cell and the environment obtains computational completeness with five symbols. Between these extreme cases of one symbol and one cell, respectively, there seems to be a trade-off between the number of cells and the number of symbols. For example, for the case of tissue P systems with two channels between a cell and the environment we show that computational completeness can be obtained with two cells and three symbols as well as with three cells and two symbols, respectively. Moreover, we also show that some variants of tissue P systems characterize the families of finite or regular sets of natural numbers.
P SYSTEMS WITH REACTION MAPS
Authors: BIANCO LUCA , FONTANA FEDERICO , MANCA VINCENZO
Published: February 2006

Some recent types of membrane systems have shown their potential in the modelling of specific processes governing biological cell behavior. These models represent the cell as a huge and complex dynamical system in which quantitative aspects, such as biochemical concentrations, must be related to the discrete informational nature of the DNA and to the function of the organelles living in the cytosol. In an effort to compute dynamical (especially oscillatory) phenomena—so far mostly treated using differential mathematical tools—by means of rewriting rules, we have enriched a known family of membrane systems (P systems), with rules that are applied proportionally to the values expressed by real functions called reaction maps. Such maps are designed to model the dynamic behavior of a biochemical phenomenon and their formalization is best worked out inside a family of P systems called PB systems. The overall rule activity is controlled by an algorithm that guarantees the system to evolve consistently with the available resources (i.e., objects). Though radically different, PB systems with reaction maps exhibit very interesting, often similar dynamic behavior as compared to systems of differential equations. Successful simulations of the Lotka-Volterra population dynamics, the Brusselator, and the Protein Kinase C activation foster potential applications of these systems in computational systems biology.
FURTHER RESULTS ON TIME-FREE P SYSTEMS
Authors: CAVALIERE MATTEO , DEUFEMIA VINCENZO
Published: February 2006

Membrane systems (currently called P systems) are parallel computing devices inspired by the structure and the functioning of living cells. A standard feature of P systems is that each rule is executed in exactly one time unit. Actually, in living cells different chemical reactions might take different times to be executed; moreover, it might be hard to know precisely such time of execution. For this reason, in [7] two models of P systems (time-free and clock-free P systems) have been defined and investigated, where the time of execution of the rules is arbitrary and the output produced by the system is always the same, independently of this time. Preliminary results concerning time-free and clock-free P system have been obtained in [6, 7, 8]. In this paper we continue these investigations by considering different combinations of possible ingredients. In particular, we present the universality of time-free P systems using bi-stable catalysts. Then, we prove that this result implies that is not possible to decide whether an arbitrary bi-stable catalytic P system is time-free. We present several results about time-free evolution-communication P systems, where the computation is a mixed application of evolution and symport/antiport rules. In this case we obtain the universality even by using non-cooperative evolution rules and antiports of weight one. Finally, we formulate several open problems.
MEALY MULTISET AUTOMATA
Authors: CIOBANU GABRIEL , GONTINEAC MIHAI
Published: February 2006

In this paper we introduce and study Mealy multiset automata, presenting some useful properties of multisets and comparing various approaches. We present the notions of bisimulation, observability, and behavior for Mealy multiset automata. We give a characterization of the bisimulation relation between two Mealy multiset automata, and a result relating their general behavior and sequential behavior. We define cascade and direct product of Mealy multiset automata. Then we introduce Mealy membrane automata corresponding to elementary P systems.
P SYSTEMS WITH INPUT IN BINARY FORM
Authors: LEPORATI ALBERTO , ZANDRON CLAUDIO , GUTIÉRREZ-NARANJO MIGUEL A.
Published: February 2006

Current P systems which solve NP–complete numerical problems represent the instances of the problems in unary notation. However, in classical complexity theory, based upon Turing machines, switching from binary to unary encoded instances generally corresponds to simplify the problem. In this paper we show that, when working with P systems, we can assume without loss of generality that instances are expressed in binary notation. More precisely, we propose a simple method to encode binary numbers using multisets, and a family of P systems which transforms such multisets into the usual unary notation. Such a family could thus be composed with the unary P systems currently proposed in the literature to obtain (uniform) families of P systems which solve NP–complete numerical problems with instances encoded in binary notation.

We introduce also a framework which can be used to design uniform families of P systems which solve NP–complete problems (both numerical and non-numerical) working directly on binary encoded instances, i.e., without first transforming them to unary notation. We illustrate our framework by designing a family of P systems which solves the 3-SAT problem. Next, we discuss the modifications needed to obtain a family of P systems which solves the PARTITION numerical problem.
GANDY'S PRINCIPLES FOR MECHANISMS AND MEMBRANE COMPUTING
Authors: OBTUŁOWICZ ADAM
Published: February 2006

The interconnections between membrane computing [9,11] and Gandy's principles for mechanisms in [3] are discussed. The embedding of the classes of hereditary finite sets (used to formulate Gandy's principles) into the class of abstract membrane systems is shown. A concept of a hereditary finite multiset is introduced as a special case of hereditary finite sets and then a representation of finite abstract membrane systems by hereditary finite multisets is presented. In this framework, a counterpart of the idea of reassemblance of hereditary finite sets is obtained for membrane systems.
DYNAMICAL PROBABILISTIC P SYSTEMS
Authors: PESCINI DARIO , BESOZZI DANIELA , MAURI GIANCARLO , ZANDRON CLAUDIO
Published: February 2006

Dynamical probabilistic P systems are discrete, stochastic, and parallel devices, where the probability values associated with the rules change during the evolution of the system. These systems are proposed as a novel approach to the analysis and simulation of the behavior of complex systems. We introduce all necessary definitions of these systems and of their dynamical aspects, we describe the functioning of the parallel and stochastic algorithm used in computer simulation, and evaluate its time complexity. Finally, we show some applications of dynamical probabilistic P systems for the investigation of the dynamics of the Lotka-Volterra system and of metapopulation systems.
CROSSED PRODUCTS BY ENDOMORPHISMS, VECTOR BUNDLES AND GROUP DUALITY, II
Authors: VASSELLI EZIO
Published: February 2006

We study C*-algebra endomorphims which are special in a weaker sense with respect to the notion introduced by Doplicher and Roberts. We assign to such endomorphisms a geometrical invariant, representing a cohomological obstruction for them to be special in the usual sense. Moreover, we construct the crossed product of a C*-algebra by the action of the dual of a (nonabelian, noncompact) group of vector bundle automorphisms. These crossed products supply a class of examples for such generalized special endomorphisms.
A POSITIVITY PROPERTY FOR FOLIATIONS ON COMPACT KÄHLER MANIFOLDS
Authors: BRUNELLA MARCO
Published: February 2006

We prove that the canonical bundle of a foliation by curves on a compact Kähler manifold is pseudoeffective, unless the foliation is a (special) foliation by rational curves.
TOPOLOGICAL STABLE RANK OF INCLUSIONS OF UNITAL C*-ALGEBRAS
Authors: OSAKA HIROYUKI , TERUYA TAMOTSU
Published: February 2006

Let 1 ∈ A ⊂ B be an inclusion of C*-algebras of C*-index-finite type with depth 2. We try to compute the topological stable rank of B (= tsr (B)) when A has topological stable rank one. We show that tsr (B) ≤ 2 when A is a tsr boundedly divisible algebra, in particular, A is a C*-minimal tensor product UHF ⊗ D with tsr (D) = 1. When G is a finite group and α is an action of G on UHF, we know that a crossed product algebra UHF ⋊α G has topological stable rank less than or equal to two.

These results are affirmative data to a generalization of a question by Blackadar in 1988.
HECKE CORRESPONDENCE FOR SYMPLECTIC BUNDLES WITH APPLICATION TO THE PICARD BUNDLES
Authors: BISWAS INDRANIL , GÓMEZ TOMÁS L.
Published: February 2006

We construct a Hecke correspondence for a moduli space of symplectic vector bundles over a curve. As an application we prove the following. Let X be a complex smooth projective curve of genus g(X) > 2 and L a line bundle over X. Let [Formula: see text] be the moduli space parametrizing stable pairs of the form (E,φ), where E is a vector bundle of rank 2n over X and φ : E ⊗ E → L a skew-symmetric nondegenerate bilinear form on the fibers of E. If deg (E) ≥ 4n(g(X)-1), then there is a projectivized Picard bundle on [Formula: see text], which is a projective bundle whose fiber over any point [Formula: see text] is ℙ(H0(X,E)). We prove that this projective bundle is stable.
COMPACT LIE GROUP ACTIONS ON CLOSED MANIFOLDS OF NON-POSITIVE CURVATURE
Authors: XU BIN
Published: February 2006

Borel proved that, if a finite group F acts effectively and continuously on a closed aspherical manifold M with centerless fundamental group π1(M), then a natural homomorphism ψ from F to the outer automorphism group Out π1(M) of π1(M), called the associated abstract kernel, is a monomorphism. In this paper, we investigate to what extent Borel's theorem holds for a compact Lie group G acting effectively and smoothly on a particular orientable aspherical manifold N admitting a Riemannian metric g0 of non-positive curvature in case that π1(N) has a non-trivial center. It turns out that if G attains the maximal dimension equal to the rank of Center π1(N) and the metric g0 is real analytic, then any element of G defining a diffemorphism homotopic to the identity of N must be contained in the identity component G0 of G. Moreover, if the inner automorphism group of π1(N) is torsion free, then the associated abstract kernel ψ : G/G0 → Out π1(N) is a monomorphism. The same result holds for the non-orientable N's under certain technical assumptions. Our result is an application of a theorem by Schoen–Yau [12] on harmonic mappings.
DENSITY FUNCTIONAL APPROXIMATION FOR NON-HARD SPHERE FLUIDS SUBJECTED TO EXTERNAL FIELDS
Authors: ZHOU SHIQI
Published: February 2006

A theoretical way is proposed, by which any hard sphere density functional approximation (DFA) can be applied to non-hard sphere fluids for the calculation of density profile in the framework of density functional theory (DFT). Used as examples, the present formalism is combined respectively with two recently proposed hard sphere DFAs to predict the density profile of Lennard–Jones (LJ) fluid, hard core square well (SW) fluid and penetrable potenial fluid subjected to diverse external fields. Extensive comparison between theoretical predictions and corresponding simulation results shows that the present theoretical way, when combined with an accurate hard sphere DFA, can perform well for calculating the density profile of the non-uniform fluids of the above mentioned potentials. Concretely speaking, for LJ and hard core SW fluid, even a less accurate FEDFA is sufficient, while for extreme potential such as the penetrable potenial, a more accurate adjustable parameter free version of LTDFA is needed to combine with the present theoretical way to predict density profile satisfactorily. The advantage of the proposed theoretical way is that the resultant DFA is applicable to both subcritical and supercritical temperature cases, thereby overcoming the disadvantages of previous two categories of DFT approach.
DISCONTINUOUS GALERKIN METHODS FOR THE LOTKA–MCKENDRICK EQUATION WITH FINITE LIFE-SPAN
Authors: KIM MI-YOUNG
Published: February 2006

We consider a model of population dynamics whose mortality function is unbounded and the solution is not regular near the maximum age. A continuous-time discontinuous Galerkin method to approximate the solution is described and analyzed. Our results show that the scheme is convergent, in L∞(L2) norm, at the rate of r + 1/2 away from the maximum age and that it is convergent at the rate of l - 1/(2q) + α/2 in L2(L2) norm, near the maximum age, if u ∈ L2(Wl,2q), where q ≥ 1, 1/2 ≤ l ≤ r + 1, r is the degree of the polynomial of the approximation space, and α is the growth rate of the mortality function; this estimate is super-convergent near the maximum age. Strong stability of the scheme is shown.
RATE-INDEPENDENT DAMAGE PROCESSES IN NONLINEAR ELASTICITY
Authors: MIELKE ALEXANDER , ROUBÍČEK TOMÁŠ
Published: February 2006

Damage of an elastic body undergoing large deformations by a "hard-device" loading possibly combined with an impact (modeled by a unilateral frictionless contact) of another, ideally rigid body is formulated as an activated, rate-independent process. The damage is assumed to absorb a specific and prescribed amount of energy. A solution is defined by energetic principles of stability and balance of stored and dissipated energies with the work of external loading, realized here through displacement on a part of the boundary. Rigorous analysis by time discretization is performed.
A TRUNCATED FOURIER/FINITE ELEMENT DISCRETIZATION OF THE STOKES EQUATIONS IN AN AXISYMMETRIC DOMAIN
Authors: BELHACHMI Z. , BERNARDI C. , DEPARIS S. , HECHT F.
Published: February 2006

We consider the Stokes problem in a three-dimensional axisymmetric domain and, by writing the Fourier expansion of its solution with respect to the angular variable, we observe that each Fourier coefficient satisfies a system of equations on the meridian domain. We propose a discretization of this problem which combines Fourier truncation and finite element methods applied to each of the two-dimensional systems. We give the detailed a priori and a posteriori analyses of the discretization and present some numerical experiments which are in good agreement with the analysis.
CONVERGENCE OF MIMETIC FINITE DIFFERENCE METHOD FOR DIFFUSION PROBLEMS ON POLYHEDRAL MESHES WITH CURVED FACES
Authors: BREZZI FRANCO , LIPNIKOV KONSTANTIN , SHASHKOV MIKHAIL
Published: February 2006

New mimetic finite difference discretizations of diffusion problems on unstructured polyhedral meshes with strongly curved (non-planar) faces are developed. The material properties are described by a full tensor. The optimal convergence estimates, the second order for a scalar variable (pressure) and the first order for a vector variable (velocity), are proved.
CAUSALLY PATHOLOGICAL SPACE–TIMES ARE PHYSICALLY RELEVANT
Authors: HUBENY VERONIKA E. , RANGAMANI MUKUND , ROSS SIMON F.
Published: February 2006

We argue that in the context of string theory, the usual restriction to globally hyperbolic space–times should be considerably relaxed. We exhibit an example of a space–time which only satisfies the causal condition, and so is arbitrarily close to admitting closed causal curves, but which has a well-behaved dual description, free of paradoxes.
BLACK HOLES RADIATE BUT DO NOT EVAPORATE
Authors: NIKOLIĆ HRVOJE
Published: February 2006

During the black hole radiation, the interior contains all the matter of the initial black hole, together with the negative energy quanta entangled with the exterior Hawking radiation. Neither the initial matter nor the negative energy quanta evaporate from the black hole interior. Therefore, the information is not lost during the radiation. The black hole mass eventually drops to zero in semiclassical gravity, but this semiclassical state has an infinite temperature and still contains all the initial matter together with the negative energy entangled with the exterior radiation.
FROM QUBITS TO BLACK HOLES: ENTROPY, ENTANGLEMENT AND ALL THAT
Authors: TERNO DANIEL R.
Published: February 2006

Entropy plays a crucial role in the characterization of information and entanglement, but it is not a scalar quantity and for many systems it is different for different relativistic observers. We discuss two examples: entropy of a single qubit and renormalized entropy as given by a uniformly accelerated observer. Loop quantum gravity predicts the Bekenstein–Hawking term for black hole entropy and the logarithmic correction to it. The latter originates in the entanglement between the pieces of spin networks that describe black hole horizon. Entanglement between gravity and matter may restore the unitarity in the black hole evaporation process. If the collapsing matter is assumed to be initially in a pure state, then entropy of the Hawking radiation is exactly the created entanglement between matter and gravity.
THE LIBRARY OF BABEL
Authors: BALASUBRAMANIAN VIJAY , JEJJALA VISHNU , SIMÓN JOAN
Published: February 2006

We show that heavy pure states of gravity can appear to be mixed states to almost all probes. Our arguments are made for AdS5 Schwarzschild black holes using the field theory dual to string theory in such spacetimes. Our results follow from applying information theoretic notions to field theory operators capable of describing very heavy states in gravity. For certain supersymmetric states of the theory, our account is exact: the microstates are described in gravity by a spacetime "foam", the precise details of which are invisible to almost all probes.
HEURISTIC APPROACH TO THE SCHWARZSCHILD GEOMETRY
Authors: VISSER MATT
Published: February 2006

In this article I present a simple Newtonian heuristic for motivating a weak-field approximation for the spacetime geometry of a point particle. The heuristic is based on Newtonian gravity, the notion of local inertial frames (the Einstein equivalence principle), plus the use of Galilean coordinate transformations to connect the freely falling local inertial frames back to the "fixed stars." Because of the heuristic and quasi-Newtonian manner in which the specific choice of spacetime geometry is motivated, we are at best justified in expecting it to be a weak-field approximation to the true spacetime geometry. However, in the case of a spherically symmetric point mass the result is coincidentally an exact solution of the full vacuum Einstein field equations — it is the Schwarzschild geometry in Painlevé–Gullstrand coordinates.

This result is much stronger than the well-known result of Michell and Laplace whereby a Newtonian argument correctly estimates the value of the Schwarzschild radius — using the heuristic presented in this article one obtains the entire Schwarzschild geometry. The heuristic also gives sensible results — a Riemann flat geometry — when applied to a constant gravitational field. Furthermore, a subtle extension of the heuristic correctly reproduces the Reissner–Nordström geometry and even the de Sitter geometry. Unfortunately the heuristic construction is not truly generic. For instance, it is incapable of generating the Kerr geometry or anti-de Sitter space.

Despite this limitation, the heuristic does have useful pedagogical value in that it provides a simple and direct plausibility argument (not a derivation) for the Schwarzschild geometry — suitable for classroom use in situations where the full power and technical machinery of general relativity might be inappropriate. The extended heuristic provides more challenging problems — suitable for use at the graduate level.
THE THIRRING–LENSE EFFECT
Authors: EMBACHER FRANZ
Published: February 2006

The Thirring–Lense effect is the phenomenon that an observer near a rotating mass, being in a state which is non-rotating with respect to the rest of the universe, experiences extra inertial forces, i.e. becomes dizzy. The first anticipation of the effect goes back to Ernst Mach; its first quantitative prediction on the basis of general relativity was given by Hans Thirring and Joseph Lense. Almost ninety years later, the effect seems to be experimentally verified.
SELF-COUPLING OF EXCITED ATOMS IN CURVED SPACE–TIME
Authors: PINTO FABRIZIO
Published: February 2006

It is well known that an excited atom, placed near a boundary, such as a mirror, undergoes an energy shift due to its interaction with the reflected field. In this paper, we use a generalized Hertz potential to prove that a radiating dipole embedded in a continuously inhomogeneous medium also experiences a position-dependent self-interaction energy shift and a corresponding self-force. Consequently, an excited atom inside a cylindrical cavity embedded in a quasi-homogeneous gravitational field, which acts as an effective "soft" boundary, is shown to experience an effective gravitational acceleration dependent on the atomic quantum state. We predict that excited trapped atom interferometers will thus provide an unexpected tool for ground-based experimentation on radiation backscattering in a Schwarzschild background.
GRAVITY FROM LOCAL LORENTZ VIOLATION
Authors: KOSTELECKÝ V. ALAN , POTTING ROBERTUS
Published: February 2006

In general relativity, gravitational waves propagate at the speed of light, and so gravitons are massless. The masslessness can be traced to symmetry under diffeomorphisms. However, another elegant possibility exists: masslessness can instead arise from spontaneous violation of local Lorentz invariance. We construct the corresponding theory of gravity. It reproduces the Einstein–Hilbert action of general relativity at low energies and temperatures. Detectable signals occur for sensitive experiments, and potentially profound implications emerge for our theoretical understanding of gravity.
PERSPECTIVES ON QUANTUM GRAVITY PHENOMENOLOGY
Authors: SUDARSKY DANIEL
Published: February 2006

The idea that quantum gravity manifestations are associated with a violation of Lorentz invariance is very strongly bounded and faces serious theoretical challenges. Other related ideas seem to be drowning in interpretational quagmires. This leads us to consider alternative lines of thought for such a phenomenological search. We discuss the underlying viewpoints and briefly mention their possible connections with other current theoretical ideas.
Autism from Developmental and Neuropsychological Perspectives
Authors: Sigman Marian , Spence Sarah J. , Wang A. Ting
Published: February 2006

In this review of the research literature on autism, we argue that the application of developmental and neuropsychological perspectives has contributed importantly to the understanding of the core deficits in autism and their underlying neural bases. The three classes of theories postulated to explain the developmental and neuropsychological deficits in autism are considered in terms of the specificity, uniqueness, and universality of these impairments in autism. Because we believe that a primary reason for our lack of understanding of the developmental trajectory in autism stems from our inability to diagnose the syndrome in the first three years of life, research approaches to early identification are discussed, as are longitudinal studies aimed at identifying later-life outcomes and their predictors. In contrast to the progress made in defining the core deficits and arriving at criteria for diagnosis, less progress has been made in identifying the causes of autism and in creating and testing interventions aimed at ameliorating the impairments of autism, possibly because these activities have been less tied to the developmental and neuropsychological models that have enlightened the investigation of core deficits.
Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells
Authors: Kiyomiya Ken-ichi , Lee Ming-Shyue , Tseng I-Chu , Zuo Hong , Barndt Robert J. , Johnson Michael D. , Dickson Robert B. , Lin Chen-Yong
Published: February 2006

Matriptase and its cognate inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), have been implicated in carcinoma onset and malignant progression. However, the pathological mechanisms of matriptase activation are not defined. Steroid sex hormones play crucial roles in prostate and breast cancer. Therefore, we investigated the questions of whether and how steroid sex hormones regulate matriptase activation in these cancer cells. Treatment of cells with 17β-estradiol had no effect on activation of matriptase in hormone-starved breast cancer cells, in part due to their high constitutive level of activated matriptase. In striking contrast, very low levels of activated matriptase were detected in hormone-starved lymph node prostatic adenocarcinoma (LNCaP) cells. Robust activation of matriptase was observed as early as 6 h after exposure of these cells to 5α-dihydrotestosterone (DHT). Activation of matriptase was closely followed by shedding of the activated matriptase with >90% of total activated matriptase present in the culture media 24 h after DHT treatment. Activated matriptase was shed in a complex with HAI-1 and may result from simultaneously proteolytic cleavages of both membrane-bound proteins. Latent matriptase and free HAI-1 were also shed into culture media. As a result of shedding, the cellular levels of matriptase and HAI-1 were significantly reduced 24 h after exposure to DHT. DHT-induced matriptase activation and shedding were significantly inhibited by the androgen antagonist bicalutamide, by the RNA transcription inhibitor actinomycin D, and by the protein synthesis inhibitor cycloheximide. These results suggest that in LNCaP cells, androgen induces matriptase activation via the androgen receptor, and requires transcription and protein synthesis.
CXCR3 chemokine receptor-induced chemotaxis in human airway epithelial cells: role of p38 MAPK and PI3K signaling pathways
Authors: Shahabuddin Syed , Ji Rong , Wang Ping , Brailoiu Eugene , Dun Na , Yang Yi , Aksoy Mark O. , Kelsen Steven G.
Published: February 2006

Human airway epithelial cells (HAEC) constitutively express the CXC chemokine receptor CXCR3, which regulates epithelial cell movement. In diseases such as chronic obstructive pulmonary disease and asthma, characterized by denudation of the epithelial lining, epithelial cell migration may contribute to airway repair and reconstitution. This study compared the potency and efficacy of three CXCR3 ligands, I-TAC/CXCL11, IP-10/CXCL10, and Mig/CXCL9, as inducers of chemotaxis in HAEC and examined the underlying signaling pathways involved. Studies were performed in cultured HAEC from normal subjects and the 16-HBE cell line. In normal HAEC, the efficacy of I-TAC-induced chemotaxis was 349 ± 88% (mean ± SE) of the medium control and approximately one-half the response to epidermal growth factor, a highly potent chemoattractant. In normal HAEC, Mig, IP-10, and I-TAC induced chemotaxis with similar potency and a rank order of efficacy of I-TAC = IP-10 > Mig. Preincubation with pertussis toxin completely blocked CXCR3-induced migration. Of interest, intracellular [Ca2+] did not rise in response to I-TAC, IP-10, or Mig. I-TAC induced a rapid phosphorylation (5–10 min) of two of the three MAPKs, i.e., p38 and ERK1/2. Pretreatment of HAEC with the p38 inhibitor SB 20358 or the PI3K inhibitor wortmannin dose-dependently inhibited the chemotactic response to I-TAC. In contrast, the ERK1/2 inhibitor U0126 had no effect on chemotaxis. These data indicate that in HAEC, CXCR3-mediated chemotaxis involves a G protein, which activates both the p38 MAPK and PI3K pathways in a calcium-independent fashion.
Physiological role of ROCKs in the cardiovascular system
Authors: Noma Kensuke , Oyama Naotsugu , Liao James K.
Published: February 2006

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.
Effect of γ-secretase inhibitors on muscarinic receptor-mediated calcium signaling in human salivary epithelial cells
Authors: Oh Young S. , Turner R. James
Published: February 2006

Altered intracellular Ca2+ signaling has been observed in cells derived from Alzheimer’s disease patients, and a possible link between γ-secretase activity and the content of intracellular Ca2+ stores has been suggested. To test this hypothesis we studied the effects of several γ-secretase inhibitors on muscarinic receptor-mediated intracellular calcium release in the human salivary gland cell line HSG. Although several inhibitors in the peptide aldehyde class partially blocked carbachol-induced Ca2+ transients, these effects did not appear to be due to γ-secretase inhibition, and overall we found no evidence that inhibition of γ-secretase activity had any significant effect on agonist-induced intracellular calcium release in HSG cells. In complementary experiments with presenilin-null cells we found that the reconstitution of γ-secretase activity by transfection with wild-type presenilin 1 likewise had no significant effect on thapsigargin-induced Ca2+ release. In a test of the specific hypothesis that the level of APP intracellular domain (AICD), the intracellular fragment of the β-amyloid precursor protein (APP) resulting from γ-secretase cleavage, can modulate the Ca2+ content of the endoplasmic reticulum, we were unable to demonstrate any effect of APP small interfering RNA on the magnitude of carbachol-induced intracellular calcium release in HSG cells. Together our data cast considerable doubt on the hypothesis that there is a direct link between γ-secretase activity and the content of intracellular Ca2+ stores.
The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms
Authors: Bondesen Brenda A. , Mills Stephen T. , Pavlath Grace K.
Published: February 2006

Loss of muscle mass occurs with disease, injury, aging, and inactivity. Restoration of normal muscle mass depends on myofiber growth, the regulation of which is incompletely understood. Cyclooxygenase (COX)-2 is one of two isoforms of COX that catalyzes the synthesis of prostaglandins, paracrine hormones that regulate diverse physiological and pathophysiological processes. Previously, we demonstrated that the COX-2 pathway regulates early stages of myofiber growth during muscle regeneration. However, whether the COX-2 pathway plays a common role in adult myofiber growth or functions specifically during muscle regeneration is unknown. Therefore, we examined the role of COX-2 during myofiber growth following atrophy in mice. Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-selective inhibitor SC-236 (6 mg·kg−1·day−1) or vehicle. COX-2 protein was expressed and SC-236 attenuated myofiber growth during reloading in both soleus and plantaris muscles. Attenuated myofiber growth in the soleus was associated with both decreased myonuclear addition and decreased inflammation, whereas neither of these processes mediated the effects of SC-236 on plantaris growth. In addition, COX-2−/− satellite cells exhibited impaired activation/proliferation in vitro, suggesting direct regulation of muscle cell activity by COX-2. Together, these data suggest that the COX-2 pathway plays a common regulatory role during various types of muscle growth via multiple mechanisms.
Serum deprivation results in redifferentiation of human umbilical vascular smooth muscle cells
Authors: Han Mei , Wen Jin-Kun , Zheng Bin , Cheng Yunhui , Zhang Chunxiang
Published: February 2006

Phenotypic change of vascular smooth muscle cells (VSMCs) from a differentiated to a dedifferentiated state accompanies the early stage of atherosclerosis and restenosis. Although much progress has been made in determining the molecular mechanisms involved in VSMC dedifferentiation, research on VSMC redifferentiation is hindered by the lack of an appropriate complete redifferentiation model. We established an in vitro model of redifferentiation by using postconfluent VSMCs from human umbilical artery. We demonstrated that serum-deprived VSMCs are capable of complete redifferentiation. After serum deprivation, postconfluent cultured human umbilical VSMCs became elongated and spindle shaped, with elevation of myofilament density, and reacquired contraction. Expressions of VSMC-specific contractile proteins, such as smooth muscle (SM) α-actin, SM-myosin heavy chain, calponin, and SM 22α, were increased and reached the levels in differentiated cells after serum deprivation. To determine the molecular mechanism of the phenotypic reversion, the levels of expression, phosphorylation, and binding activity of serum response factor (SRF), a key phenotypic modulator for VSMCs, were measured. The results showed that SRF binding activity with CArG motif was significantly increased after serum deprivation, whereas no changes were found in SRF expression and phosphorylation. The increased SRF binding activity was accompanied by an increase in expression of its coactivators such as myocardin. Furthermore, the phenotypic reversion was markedly inhibited by decoy double-strand oligodeoxynucleotides containing SM α-actin CArG motif, which was able to competitively bind to SRF. The results suggested that serum deprivation results in redifferentiation of human umbilical VSMCs. This novel model of VSMC phenotypic reversion should be valuable for research on vascular disease.
Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep
Authors: Carey Luke C. , Su Yixin , Valego Nancy K. , Rose James C.
Published: February 2006

The late-gestation plasma cortisol surge in the sheep fetus is critical for stimulating organ development and parturition. Increased adrenal responsiveness is one of the key reasons for the surge; however, the underlying mechanisms are not fully understood. Our recent studies suggest that ACTH-mediated increased expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) may play a role in enhancing responsiveness. Hence, we examined effects of ACTH infusion in fetal sheep on mRNA expression of these two mediators of adrenal responsiveness and assessed the functional consequences of this treatment in vitro. Fetuses of ∼118 and 138 days of gestational age (dGA) were infused with ACTH-(1–24) for 24 h. Controls received saline infusion. Arterial blood was sampled throughout the infusion. Adrenals were isolated and analyzed for ACTH-R and StAR mRNA, or cells were cultured for 48 h. Cells were stimulated with ACTH, and medium was collected for cortisol measurement. Fetal plasma ACTH and cortisol concentrations increased over the infusion period in both groups. ACTH-R mRNA levels were significantly higher in ACTH-infused fetuses in both the 118 and 138 dGA groups. StAR mRNA increased significantly in both the 118 and 138 dGA groups. Adrenal cells from ACTH-infused fetuses were significantly more responsive to ACTH stimulation in terms of cortisol secretion than those from saline-infused controls. These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH-R and StAR mRNA and are coupled to heightened adrenal responsiveness.
Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense
Authors: Kao John Y. , Rathinavelu Sivaprakash , Eaton Kathryn A. , Bai Longchuan , Zavros Yana , Takami Mimi , Pierzchala Anna , Merchant Juanita L.
Published: February 2006

Helicobacter pylori evades host immune defenses and causes chronic gastritis. Immunity against intestinal pathogens is largely mediated by dendritic cells, yet the role of dendritic cells in acute H. pylori infection is largely unknown. We observed the recruitment of dendritic cells to the gastric mucosa of H. pylori-infected mice. Bone marrow-derived dendritic cells from mice responded to live H. pylori by upregulating the expression of proinflammatory cytokine mRNA (i.e., IL-1α, IL-1β, and IL-6). The supernatant from dendritic cells stimulated with H. pylori for 18 h contained twofold higher levels of IL-12p70 than IL-10 and induced the proliferation of syngeneic splenocytes and type 1 T helper cell cytokine release (IFN-γ and TNF-α). These responses were significantly lower compared with those induced by Acinetobacter lwoffi, another gastritis-causing pathogen more susceptible to host defenses. Analysis of whole H. pylori sonicate revealed the presence of a heat-stable factor secreted from H. pylori that specifically inhibited IL-12 but not IL-10 release from dendritic cells activated by A. lwoffi. Our findings suggest that dendritic cells participate in the host immune response against H. pylori and that their suppression by H. pylori may explain why infected hosts fail to prevent bacterial colonization.
Visually guided whole cell patch clamp of mouse supraoptic nucleus neurons in cultured and acute conditions
Authors: Stachniak Tevye J. E. , Bourque Charles W.
Published: February 2006

Recent advances in neuronal culturing techniques have supplied a new set of tools for studying neural tissue, providing effective means to study molecular aspects of regulatory elements in the supraoptic nucleus of the hypothalamus (SON). To combine molecular biology techniques with electrophysiological recording, we modified an organotypic culture protocol to permit transfection and whole cell patch-clamp recordings from SON cells. Neonatal mouse brain coronal sections containing the SON were dissected out, placed on a filter insert in culture medium, and incubated for at least 4 days to allow attachment to the insert. The SON was identifiable using gross anatomical landmarks, which remained intact throughout the culturing period. Immunohistochemical staining identified both vasopressinergic and oxytocinergic cells present in the cultures, typically appearing in well-defined clusters. Whole cell recordings from these cultures demonstrated that certain properties of the neonatal mouse SON were comparable to adult mouse magnocellular neurons. SON neurons in both neonatal cultures and acute adult slices showed similar sustained outward rectification above −60 mV and action potential broadening during evoked activity. Membrane potential, input resistance, and rapidly inactivating potassium current density ( IA) were reduced in the cultures, whereas whole cell capacitance and spontaneous synaptic excitation were increased, perhaps reflecting developmental changes in cell physiology that warrant further study. The use of the outlined organotypic culturing procedures will allow the study of such electrophysiological properties of mouse SON using whole cell patch-clamp, in addition to various molecular, techniques that require longer incubation times.
Effects of combined inhibition of ATP-sensitive potassium channels, nitric oxide, and prostaglandins on hyperemia during moderate exercise
Authors: Schrage William G. , Dietz Niki M. , Joyner Michael J.
Published: February 2006

ATP-sensitive potassium (KATP) channels have been suggested to contribute to coronary and skeletal muscle vasodilation during exercise, either alone or interacting in a parallel or redundant process with nitric oxide (NO), prostaglandins (PGs), and adenosine. We tested the hypothesis that KATP channels, alone or in combination with NO and PGs, regulate exercise hyperemia in forearm muscle. Eighteen healthy young adults performed 20 min of moderate dynamic forearm exercise, with forearm blood flow (FBF) measured via Doppler ultrasound. After steady-state FBF was achieved for 5 min (saline control), the KATP inhibitor glibenclamide (Glib) was infused into the brachial artery for 5 min (10 μg·dl−1·min−1), followed by saline infusion during the final 10 min of exercise ( n = 9). Exercise increased FBF from 71 ± 11 to 239 ± 24 ml/min, and FBF was not altered by 5 min of Glib. Systemic plasma Glib levels were above the therapeutic range, and Glib increased insulin levels by ∼50%, whereas blood glucose was unchanged (88 ± 2 vs. 90 ± 2 mg/dl). In nine additional subjects, Glib was followed by combined infusion of NG-nitro-l-arginine methyl ester (l-NAME) plus ketorolac (to inhibit NO and PGs, respectively). As above, Glib had no effect on FBF but addition of l-NAME + ketorolac (i.e., triple blockade) reduced FBF by ∼15% below steady-state exercise levels in seven of nine subjects. Interestingly, triple blockade in two subjects caused FBF to transiently and dramatically decrease. This was followed by an acute recovery of flow above steady-state exercise values. We conclude 1) opening of KATP channels is not obligatory for forearm exercise hyperemia, and 2) triple blockade of NO, PGs, and KATP channels does not reduce hyperemia more than the inhibition of NO and PGs in most subjects. However, some subjects are sensitive to triple blockade, but they are able to restore FBF acutely during exercise. Future studies are required to determine the nature of these compensatory mechanisms in the affected individuals.
Olfactory Nerve Stimulation-Evoked mGluR1 Slow Potentials, Oscillations, and Calcium Signaling in Mouse Olfactory Bulb Mitral Cells
Authors: Yuan Q. , Knöpfel T.
Published: February 2006

Fast synaptic transmission between olfactory receptor neurons and mitral cells (MCs) is mediated through AMPA and NMDA ionotropic glutamate receptors. MCs also express high levels of metabotropic glutamate receptor 1 (mGluR1) whose functional significance is less understood. Here we characterized a slow mGluR1-mediated potential that was evoked by high-frequency (100-Hz) olfactory nerve (ON) stimulation in the presence of NBQX and d-APV, blockers of ionotropic glutamate receptors, and that was associated with a local Ca2+ transient in the MC dendritic tuft. High-frequency ON stimulation in the presence of NBQX and d-APV also evoked a slow, nearly 2-Hz oscillation of MC membrane potential that was abolished by the mGluR1 antagonist LY367385 (50 μM). Both mGluR slow potential and slow oscillation persisted in the presence of gabazine (10 μM), a GABAA receptor antagonist, and intracellular QX-314 (10 mM), a Na+ channel blocker. In contrast to a slow mGluR1 potential in cerebellar Purkinje neurons, the MC mGluR1 potential was not depressed by SKF96365 (≤250 μM) and thus is likely not mediated by TRPC1 cation channels, nor was it potentiated by an elevation of intracellular Ca2+ level. Imaging with the Na+ indicator SBFI revealed a Na+ transient in the MC dendrite accompanying the mGluR1 slow potential. We conclude that the MC mGluR1 potential triggered by glutamate released from the ON supports oscillations and synchronizations of MCs associated within one glomerulus.