bluuebunny/crossref_metadata_2025 huggingface dataset:
APPROXIMATE GRAVITATIONAL WAVES VIA DEFORMATIONS OF EMBEDDINGS
Authors: KERNER RICHARD , VITALE SALVATORE
Published: April 2009

Many Einstein spaces can be embedded globally in pseudo-Euclidean spaces of dimension N > 4. The geometrical quantities characterizing the embedded manifold can be expressed by means of derivatives of the embedding functions zA (xµ), A, B, = 1, 2, …N, µ, ν, …= 0, 1, 2, 3. An infinitesimal deformation of embedding can be expanded into a series [Formula: see text], giving rise to a similar expansion of geometrical quantities of the embedded Einstein space, and the Einstein equations in vacuo, too. We show how gravitational wave solutions appear naturally in this context.
SOLITON SOLUTIONS IN AN O(3) σ MODEL AND THE FERMION LOCALIZATION ON THE TOPOLOGICAL DEFECTS
Authors: KODAMA YUTA , KOKUBU KENTO , SAWADO NOBUYUKI , TODA KOUICHI
Published: April 2009

We investigate a fermionic O(3) σ model in 2+1 dimensions, taking into account the valence and the Casimir energies. The model exhibits the soliton solutions with various winding numbers. Lagrangian, which we used above, is extended into 6 dimensional brane world scenario and the fermion localization problem. In terms of the level crossing picture, emergence of the massive localized modes as well as the zero mode are found.
RELATIVISTIC ATOMIC PHYSICS: FROM ATOMIC CLOCK SYNCHRONIZATION TOWARDS RELATIVISTIC ENTANGLEMENT
Authors: LUSANNA LUCA
Published: April 2009

A review is given of the implications of the absence of an intrinsic notion of instantaneous 3-space, so that a clock synchronization convention has to be introduced, for relativistic theories.
PLANE GRAVITATIONAL RADIATION FROM NEUTRINOS SOURCE WITH KALB-RAMOND COUPLING
Authors: FERREIRA C. N. , HELAYËL-NETO J. A. , TOMIMURA N. A.
Published: April 2009

In this work, we propose a model based on a non-minimal coupling of neutrinos to a Kalb-Ramond field. The latter is taken as a possible source for gravitational radiation. As an immediate illustration of this system, we have studied the case where gravitational (plane) wave solutions behave as damped harmonic oscillators.
GRAVITATIONAL WAVES FROM COSMOLOGICAL PHASE TRANSITIONS
Authors: MÉGEVAND ARIEL
Published: April 2009

I discuss the gravitational radiation produced in a first-order phase transition due to the turbulence that is caused by bubble expansion. I compare the cases of deflagration and detonation bubbles.
THE NATURE OF THE COSMOLOGICAL CONSTANT PROBLEM
Authors: MAIA M. D. , CAPISTRANO A. J. S. , MONTE E. M.
Published: April 2009

General relativity postulates the Minkowski space-time as the standard (flat) geometry against which we compare all curved space-times and also as the gravitational ground state where particles, quantum fields and their vacua are defined. On the other hand, experimental evidences tell that there exists a non-zero cosmological constant, which implies in a deSitter ground state, which not compatible with the assumed Minkowski structure. Such inconsistency is an evidence of the missing standard of curvature in Riemann's geometry, which in general relativity manifests itself in the form of the cosmological constant problem. We show how the lack of a curvature standard in Riemann's geometry can be fixed by Nash's theorem on metric perturbations. The resulting higher dimensional gravitational theory is more general than general relativity, similar to brane-world gravity, but where the propagation of the gravitational field along the extra dimensions is a mathematical necessity, rather than a postulate. After a brief introduction to Nash's theorem, we show that the vacuum energy density must remain confined to four-dimensional space-times, but the cosmological constant resulting from the contracted Bianchi identity represents a gravitational term which is not confined. In this case, the comparison between the vacuum energy and the cosmological constant in general relativity does not make sense. Instead, the geometrical fix provided by Nash's theorem suggests that the vacuum energy density contributes to the perturbations of the gravitational field.
POLEMIC NOTES ON IR PERTURBATIVE QUANTUM GRAVITY
Authors: SHAPIRO ILYA L.
Published: April 2009

Quantum gravity is an important and to great extent unsolved problem. There are many different approaches to the quantization of the metric field, both perturbative and nonperturbative. The current situation in the perturbative quantum gravity is characterized by a number of different models, some of them well elaborated but no one perfect nor mathematically neither phenomenologically, mainly because there are no theoretically derived observables which can be experimentally measured. A very interesting one is an effective approach which separates the low-energy quantum effects from the UV sector. In this way one can calculate quantities which are potentially relevant for establishing certain universal features of quantum gravity. In this presentation we give a polemic consideration of the effective approach to the infrared quantum gravity. We question the validity of the recent results in this area and also discuss how one can check the alleged universality of the effective approach.
ON THE 1-LOOP CALCULATIONS OF SOFTLY BROKEN FERMION-TORSION THEORY IN CURVED SPACE USING THE STÜCKELBERG PROCEDURE
Authors: DE BERREDO-PEIXOTO G.
Published: April 2009

The soft breaking of gauge or other symmetries is the typical Quantum Field Theory phenomenon. In many cases one can apply the Stückelberg procedure, which means introducing some additional field (or fields) and restore the gauge symmetry. The original softly broken theory corresponds to a particular choice of the gauge fixing condition. In this paper we use this scheme for performing quantum calculations for fermion-torsion theory, softly broken by the torsion mass in arbitrary curved spacetime.
ENERGY AND MOMENTUM LOSS BY GRAVITATIONAL RADIATION EMISSION IN THE COLLISION OF TWO SCHWARZSCHILD BLACK HOLES
Authors: ARANHA R. F. , DAMIÃO SOARES I. , OLIVEIRA H. P. , TONINI E. V.
Published: April 2009

We analyze the head-on collision of two boosted Schwarzschild black holes and the mass-energy loss of the system by gravitational wave emission, in the realm of Robinson-Trautman (RT) spacetimes. The characteristic initial data for the problem are constructed, and evolved by RT equation integrated by numerical codes based on the Galerkin method. The emission of gravitational waves is typical bremsstrahlung at early times and the final configuration is that of a boosted black hole with larger (Bondi) rest mass and smaller velocity parameter. The efficiency Δ of the process of energy extraction by gravitational radiation is evaluated and satisfies a nonextensive distribution with entropic index q ≃ 1/2. The final momentum of the remnant black hole has a maximum which depends on the ratio of the masses of the initial black holes.
STATIC SPHERICALLY SYMMETRIC SOLUTIONS FOR CONFORMAL GRAVITY IN THREE DIMENSIONS
Authors: OLIVA JULIO , TEMPO DAVID , TRONCOSO RICARDO
Published: April 2009

Static spherically symmetric solutions for conformal gravity in three dimensions are found. Black holes and wormholes are included within this class. Asymptotically the black holes are spacetimes of arbitrary constant curvature, and they are conformally related to the matching of different solutions of constant curvature by means of an improper conformal transformation. The wormholes can be constructed from suitable identifications of a static universe of negative spatial curvature, and it is shown that they correspond to the conformal matching of two black hole solutions with the same mass.
ON THE BLACK HOLE INTERIOR SPACETIME
Authors: CULETU HRISTU
Published: April 2009

A spacetime endowed with an anisotropic fluid is proposed for the interior of a black hole. The geometry has an instantaneous Minkowski form and is a solution of Einstein's equations with a stress tensor on the r.h.s. obeying all the energy conditions. The interior fluid is compressible, with time dependent shear and bulk viscosity coefficients. The energy density ρ and the "radial" pressure p are proportional to 1/t2, with no pressures on θ- and ϕ- directions. The model leads to a time dependent cosmological constant.
RELATIVISTIC DYNAMICS WITH COSMOLOGICAL CONSTANT: SPINNING TEST PARTICLES AND PERFECT FLUID TORI
Authors: KOVÁŘ JIŘÍ , SLANÝ PETR , STUCHLÍK ZDENĔK
Published: April 2009

Results of our recent studies concerning possible effects of Λ > 0 for equilibrium positions of spinning test particles and stationary configurations of perfect-fluid tori are presented.
ENERGY-MOMENTUM COMPLEXES FOR A STRINGY BLACK HOLE GEOMETRY IN A LOW-ENERGY EFFECTIVE STRING THEORY
Authors: RADINSCHI I. , GRAMMENOS TH.
Published: April 2009

The energy and momentum distributions for a four-dimensional, magnetically charged, stringy black hole geometry, in a low-energy effective string theory, are calculated. To this purpose, the energy-momentum complexes of Einstein, Landau-Lifshitz, Weinberg and Møller are applied. It is found that, in all four prescriptions, the momentum distribution vanishes, while the energies obtained differ, but all are functions of the mass, the scalar charge, and the boost parameter.
COSMIC DEFECT COSMOLOGY
Authors: TARTAGLIA A.
Published: April 2009

The accelerated expansion of the universe is interpreted as an effect of a defect in space-time treated as a four-dimensional continuum endowed with physical properties. The analogy is with texture defects in material continua, like dislocations and disclinations, described in terms of a singular displacement vector field. A Lagrangian for empty space-time is proposed exploiting one further analogy between the phase space of a Robertson-Walker universe and the phase space of a point particle moving across an homogeneous isotropic medium. The model, named Cosmic Defect theory, produces, as a byproduct, also inflation near the initial singularity. The theory has been applied to fit the luminosity data of 192 type Ia supernovae. The results are satisfying and comparable with the ones obtained by means of the Λ Cold Dark Matter standard model.
CONSTRAINTS ON DARK ENERGY AND COSMIC TOPOLOGY
Authors: REBOUÇAS MARCELO J.
Published: April 2009

A non-trivial spatial topology of the Universe is a potentially observable attribute, which can be probed through the circles-in-the-sky for all locally homogeneous and isotropic universes with no assumptions on the cosmological parameters. We show how one can use a possible circles-in-the-sky detection of the spatial topology of globally homogeneous universes to set constraints on the dark energy equation of state parameters.
SPEEDING THE FRIEDMANN EXPANSION BY CHIRAL TENSOR PARTICLES
Authors: CHIZHOV M. V. , KIRILOVA D. P.
Published: April 2009

The status of the chiral tensor particles in the extended electroweak model, their experimental constraints, signatures and the possibilities for their detection at the new colliders are shortly reviewed. The cosmological effects of the additional particles are discussed. Namely, their characteristic interactions with the other components of the early Universe plasma and the corresponding cosmic times and temperatures are determined. The dynamical cosmological effect, namely the speeding of the Friedmann expansion due to the density increase caused by the chiral tensor particles and the additional Higgs doublet is discussed. The presence of the chiral tensor particles is allowed from cosmological considerations and welcomed by the particle physics phenomenology.
THE ANTARES UNDERWATER NEUTRINO TELESCOPE
Authors:   for the ANTARES COLLABORATION, MONTARULI TERESA
Published: April 2009

ANTARES is the first undersea neutrino telescope. It is in its complete configuration since May 2008 at about 2.5 km below the sea surface close to Marseille. Data from 12 lines are being analyzed and are producing first results. Here we discuss first analysis results for 5 lines and 10 lines, and we also comment on the performance of the full detector. We show that the detector has capabilities for discriminating upgoing neutrino events from the much larger amount of downgoing atmospheric muons and that data and simulation are in good agreement. We then discuss the physics reach of the detector for what concerns point-like source and dark matter searches.
GALACTIC NONLINEAR DYNAMIC MODEL
Authors: DE MELO C. A. M. , RESENDE S. T.
Published: April 2009

We develop a model for spiral galaxies based on a nonlinear realization of the Newtonian dynamics starting from the momentum and mass conservations in the phase space. The radial solution exhibits a rotation curve in qualitative accordance with the observational data.
VACUUM SOLUTIONS WITH NONTRIVIAL BOUNDARIES FOR THE EINSTEIN-GAUSS-BONNET THEORY
Authors: DOTTI GUSTAVO , OLIVA JULIO , TRONCOSO RICARDO
Published: April 2009

The classification of certain class of static solutions for the Einstein-Gauss-Bonnet theory in vacuum is presented. The spacelike section of the class of metrics under consideration is a warped product of the real line with a nontrivial base manifold. For arbitrary values of the Gauss-Bonnet coupling, the base manifold must be Einstein with an additional scalar restriction. The geometry of the boundary can be relaxed only when the Gauss-Bonnet coupling is related with the cosmological and Newton constants, so that the theory admits a unique maximally symmetric solution. This additional freedom in the boundary metric allows the existence of three main branches of geometries in the bulk, containing new black holes and wormholes in vacuum.
TIDAL TENSOR APPROACH TO GRAVITOELECTROMAGNETISM
Authors: COSTA L. FILIPE O. , HERDEIRO CARLOS A. R.
Published: April 2009

We summarize the gravito-electromagnetic analogy based on tidal tensors. This analogy leads to an exact and fully general form for the gravitational analogues of Maxwell's equations, which allows for a transparent comparison between the two interactions. Special cases of matching between gravitational and electromagnetic tidal tensors are discussed.
MAXIMUM LIKELIHOOD ESTIMATION FOR SIMPLEX DISTRIBUTION NONLINEAR MIXED MODELS VIA AN EM ALGORITHM
Authors: WEI HONGJIE , ZHANG WENZHUAN
Published: April 2009

Longitudinal continuous proportional data is common in many fields such as biomedical research, psychological research and so on. As shown in [16], such data can be fitted with simplex models. Based on the original models of [16] which assumed a fixed effect for every subject, this paper extends the models by adding random effects and proposes simplex distribution nonlinear mixed models which are one kind of nonlinear reproductive dispersion mixed models. By treating the random effects in the models as hypothetical missing data and applying Metropolis–Hastings (M–H) algorithm, this paper develops an EM algorithm with Markov chain Monte–Carlo method for maximum likelihood estimation in the models. The method is illustrated with the same data from an ophthalmology study on the use of intraocular gas in retinal surgeries in [16] for ease of comparison.
Smad2 and 3 transcription factors control muscle mass in adulthood
Authors: Sartori Roberta , Milan Giulia , Patron Maria , Mammucari Cristina , Blaauw Bert , Abraham Reimar , Sandri Marco
Published: April 2009

Loss of muscle mass occurs in a variety of diseases, including cancer, chronic heart failure, aquired immunodeficiency syndrome, diabetes, and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis, and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover, recent results confirm that other transforming growth factor-β (TGF-β) members control muscle mass. Using genetic tools, we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF-β and induce an atrophy program that is muscle RING-finger protein 1 (MuRF1) independent. Furthermore, Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mammalian target of rapamycin (mTOR) signaling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation, especially when they are combined with IGF-1-Akt activators.
Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation
Authors: Shiratsuchi Hiroe , Kouatli Yasser , Yu Guang Xiang , Marsh Harold M. , Basson Marc D.
Published: April 2009

Surgical stress and anesthesia result in systemic immunosuppression. Propofol, a commonly used anesthetic agent, alters immune cell functions. Previously, we demonstrated that extracellular pressure increases macrophage phagocytosis. We hypothesized that propofol might influence pressure-induced macrophage phagocytosis in monocytes from patients undergoing surgery. Pressure (20 mmHg above ambient pressure) augmented phagocytosis in monocytes from non-propofol-anesthetized patients but reduced phagocytosis in monocytes from propofol-anesthetized patients. In vitro, propofol stimulated phagocytosis but reversed pressure-induced phagocytosis in THP-1 macrophages and monocytes from healthy volunteers. The GABAA receptor antagonists picrotoxin and SR-95531 did not affect basal THP-1 phagocytosis or prevent pressure-stimulated phagocytosis. However, picrotoxin and SR-95531 negated the inhibitory effect of pressure in propofol-treated cells without altering propofol-induced phagocytosis. Phosphorylation of the adaptor protein p130cas was inversely related to phagocytosis: it was inhibited by pressure or propofol but increased by pressure + propofol compared with propofol alone. Reduction of p130cas by small interfering RNA in THP-1 macrophages increased basal phagocytosis and prevented pressure and propofol effects. In conclusion, propofol may alter macrophage responses to pressure via the GABAA receptor and p130cas, whereas pressure also acts via p130cas but independently of GABAA receptors. p130cas may be an important target for modulation of macrophage function in anesthetized patients.
A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis
Authors: Ungaro Ryan , Fukata Masayuki , Hsu David , Hernandez Yasmin , Breglio Keith , Chen Anli , Xu Ruliang , Sotolongo John , Espana Cecillia , Zaias Julia , Elson Greg , Mayer Lloyd , Kosco-Vilbois Marie , Abreu Maria T.
Published: April 2009

Dysregulated innate immune responses to commensal bacteria contribute to the development of inflammatory bowel disease (IBD). TLR4 is overexpressed in the intestinal mucosa of IBD patients and may contribute to uncontrolled inflammation. However, TLR4 is also an important mediator of intestinal repair. The aim of this study is to examine the effect of a TLR4 antagonist on inflammation and intestinal repair in two murine models of IBD. Colitis was induced in C57BL/6J mice with dextran sodium sulfate (DSS) or by transferring CD45RbhiT cells into RAG1−/− mice. An antibody (Ab) against the TLR4/MD-2 complex or isotype control Ab was administered intraperitoneally during DSS treatment, recovery from DSS colitis, or induction of colitis in RAG1−/− mice. Colitis severity was assessed by disease activity index (DAI) and histology. The effect of the Ab on the inflammatory infiltrate was determined by cell isolation and immunohistochemistry. Mucosal expression of inflammatory mediators was analyzed by real-time PCR and ELISA. Blocking TLR4 at the beginning of DSS administration delayed the development of colitis with significantly lower DAI scores. Anti-TLR4 Ab treatment decreased macrophage and dendritic cell infiltrate and reduced mucosal expression of CCL2, CCL20, TNF-α, and IL-6. Anti-TLR4 Ab treatment during recovery from DSS colitis resulted in defective mucosal healing with lower expression of COX-2, PGE2, and amphiregulin. In contrast, TLR4 blockade had minimal efficacy in ameliorating inflammation in the adoptive transfer model of chronic colitis. Our findings suggest that anti-TLR4 therapy may decrease inflammation in IBD but may also interfere with colonic mucosal healing.
Endogenous IGF-I and αvβ3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis
Authors: Hazelgrove Krystina B. , Flynn Robert S. , Qiao Li-Ya , Grider John R. , Kuemmerle John F.
Published: April 2009

Endogenous insulin-like growth factor-I (IGF-I) regulates intestinal smooth muscle growth by concomitantly stimulating proliferation and inhibiting apoptosis. IGF-I-stimulated growth is augmented by the αvβ3 integrin ligands vitronectin and fibronectin. IGF-I expression in smooth muscle is increased in both TNBS-induced colitis and Crohn's disease. We hypothesized that intestinal inflammation increased vitronectin and fibronectin expression by smooth muscle and, along with IGF-I upregulation, increased intestinal muscle growth. Intestinal smooth muscle cells were examined 7 days following the induction of TNBS-induced colitis. Although αvβ3 integrin expression was not altered by TNBS-induced colitis, vitronectin and fibronectin levels were increased by 80 ± 10% and 90 ± 15%, above control levels, respectively. Basal IGF-I receptor phosphorylation in inflamed muscle from TNBS-treated rats was increased by 86 ± 8% over vehicle-treated controls. Basal ERK1/2, p70S6 kinase, and GSK-3β phosphorylation in muscle cells of TNBS-treated rats were also increased by 140–180%. TNBS treatment increased basal muscle cell proliferation by 130 ± 15% and decreased apoptosis by 20 ± 2% compared with that in vehicle-treated controls. The changes in proliferation and apoptosis were reversed by an IGF-I receptor tyrosine kinase inhibitor or an αvβ3 integrin antagonist. The results suggest that smooth muscle hyperplasia in TNBS-induced colitis partly results from the upregulation of endogenous IGF-I and ligands of αvβ3 integrin that mediate increased smooth muscle cell proliferation and decreased apoptosis. This paper has identified one mechanism regulating smooth muscle hyperplasia, a feature of stricture formation that occurs in the chronically inflamed intestine of TNBS-induced colitis and potentially Crohn's disease.
Prostaglandin regulation of gastric slow waves and peristalsis
Authors: Forrest Abigail S. , Hennig Grant W. , Jokela-Willis Sari , Park Chong Doo , Sanders Kenton M.
Published: April 2009

Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE2 on slow waves in the murine stomach. PGE2 increased slow-wave frequency, and this effect was mimicked by EP3, but not by EP2, receptor agonists. Chronotropic effects were due to EP3 receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W V mice. Although the integrated chronotropic effects of EP3 receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP3 receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis.
Electrohydraulic pump-driven closed-loop blood pressure-regulatory system
Authors: Siu K. L. , Ahn J. M. , Chon K. H.
Published: April 2009

In this paper, we describe our design for a new electrohydraulic (EH) pump-driven renal perfusion pressure (RPP)-regulatory system capable of implementing precise and rapid RPP regulation in experimental animals. Without this automated system, RPP is manually controlled via a blood pressure clamp, and the imprecision in this method leads to compromised RPP data. This motivated us to develop an EH pump-driven closed-loop blood pressure regulatory system based on flow-mediated occlusion using the vascular occlusive cuff technique. A closed-loop servo-controller system based on a proportional plus integral (PI) controller was designed using the dynamic feedback RPP signal from animals. In vivo performance was evaluated via flow-mediated RPP occlusion, maintenance, and release responses during baseline and ANG II-infused conditions. A step change of −30 mmHg, referenced to normal RPP, was applied to Sprague-Dawley rats with the proposed system to assess the performance of the PI controller. The PI's performance was compared against manual control of blood pressure clamp to regulate RPP. Rapid RPP occlusion (within 3 s) and a release time of ∼0.3 s were obtained for the PI controller for both baseline and ANG II infusion conditions, in which the former condition was significantly better than manual control. We concluded that the proposed EH RPP-regulatory system could fulfill in vivo needs to study various pressure-flow relationships in diverse fields of physiology, in particular, studying the dynamics of the renal autoregulatory mechanisms.
Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney
Authors: Kim Hyun Ju , Moradi Hamid , Yuan Jun , Norris Keith , Vaziri Nosratola D.
Published: April 2009

A significant reduction of renal mass results in proteinuria, glomerulosclerosis, and tubulointerstitial injury, culminating in end-stage chronic renal failure (CRF). The accumulation of lipids in the kidney can cause renal disease. Uptake of oxidized lipoproteins via scavenger receptors, reabsorption of filtered protein-bound lipids via the megalin-cubilin complex, and increased glucose load per nephron can promote lipid accumulation in glomerular, tubular, and interstitial cells in CRF. Cellular lipid homeostasis is regulated by lipid influx, synthesis, catabolism, and efflux. We examined lipid-regulatory factors in the remnant kidney of rats 11 wk after nephrectomy (CRF) or sham operation. CRF resulted in azotemia, proteinuria, lipid accumulation in the kidney, upregulation of megalin, cubilin, mediators of lipid influx (scavenger receptor class A and lectin-like oxidized receptor-1), lipid efflux (liver X receptor α/β and ATP-binding cassette transporter), and fatty acid biosynthesis (carbohydrate-response element binding protein, fatty acid synthase, and acetyl-CoA carboxylase). However, factors involved in cholesterol biosynthesis (sterol regulatory element binding protein, 3-hydroxy-3-methylglutaryl coenzyme A reductase, SCAP, Insig-1, and Insig-2) and fatty acid oxidation (peroxisome proliferator-activated receptor, acyl-CoA oxidase, and liver-type fatty acid binding protein) were reduced in the remnant kidney. Thus CRF results in heavy lipid accumulation in the remnant kidney, which is mediated by upregulation of pathways involved in tubular reabsorption of filtered protein-bound lipids, influx of oxidized lipoproteins and synthesis of fatty acids, and downregulation of pathways involved in fatty acid catabolism.
Respiratory muscle fiber remodeling in chronic hyperinflation: dysfunction or adaptation?
Authors: Clanton Thomas L. , Levine Sanford
Published: April 2009

The diaphragm and other respiratory muscles undergo extensive remodeling in both animal models of emphysema and in human chronic obstructive pulmonary disease, but the nature of the remodeling is different in many respects. One common feature is a shift toward improved endurance characteristics and increased oxidative capacity. Furthermore, both animals and humans respond to chronic hyperinflation by diaphragm shortening. Although in rodent models this clearly arises by deletion of sarcomeres in series, the mechanism has not been proven conclusively in human chronic obstructive pulmonary disease. Unique characteristics of the adaptation in human diaphragms include shifts to more predominant slow, type I fibers, expressing slower myosin heavy chain isoforms, and type I and type II fiber atrophy. Although some laboratories report reductions in specific force, this may be accounted for by decreases in myosin heavy chain content as the muscles become more oxidative and more efficient. More recent findings have reported reductions in Ca2+sensitivity and reduced myofibrillar elastic recoil. In contrast, in rodent models of disease, there is no consistent evidence for loss of specific force, no consistent shift in fiber populations, and atrophy is predominantly seen only in fast, type IIX fibers. This review challenges the hypothesis that the adaptations in human diaphragm represent a form of dysfunction, secondary to systemic disease, and suggest that most findings can as well be attributed to adaptive processes of a complex muscle responding to unique alterations in its working environment.
Electromechanical delay revisited using very high frame rate ultrasound
Authors: Nordez Antoine , Gallot Thomas , Catheline Stefan , Guével Arnaud , Cornu Christophe , Hug François
Published: April 2009

Electromechanical delay (EMD) represents the time lag between muscle activation and muscle force production and is used to assess muscle function in healthy and pathological subjects. There is no experimental methodology to quantify the actual contribution of each series elastic component structures that together contribute to the EMD. We designed the present study to determine, using very high frame rate ultrasound (4 kHz), the onset of muscle fascicles and tendon motion induced by electrical stimulation. Nine subjects underwent two bouts composed of five electrically evoked contractions with the echographic probe maintained over 1) the gastrocnemius medialis muscle belly (muscle trials) and 2) the myotendinous junction of the gastrocnemius medialis muscle (tendon trials). EMD was 11.63 ± 1.51 and 11.67 ± 1.27 ms for muscle trials and tendon trials, respectively. Significant difference ( P < 0.001) was found between the onset of muscle fascicles motion (6.05 ± 0.64 ms) and the onset of myotendinous junction motion (8.42 ± 1.63 ms). The noninvasive methodology used in the present study enabled us to determine the relative contribution of the passive part of the series elastic component (47.5 ± 6.0% of EMD) and each of the two main structures of this component (aponeurosis and tendon, representing 20.3 ± 10.7% and 27.6 ± 11.4% of EMD, respectively). The relative contributions of the synaptic transmission, the excitation-contraction coupling, and the active part of the series elastic component could not be directly quantified with our results. However, they suggest a minor role of the active part of the series elastic component that needs to be confirmed by further experiments.
AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training
Authors: Lee-Young Robert S. , Canny Benedict J. , Myers Damian E. , McConell Glenn K.
Published: April 2009

AMP-activated protein kinase (AMPK) has been extensively studied in whole muscle biopsy samples of humans, yet the fiber type-specific expression and/or activation of AMPK is unknown. We examined basal and exercise AMPK-α Thr172 phosphorylation and AMPK subunit expression (α1, α2, and γ3) in type I, IIa, and IIx fibers of human skeletal muscle before and after 10 days of exercise training. Before training basal AMPK phosphorylation was greatest in type IIa fibers ( P < 0.05 vs. type I and IIx), while an acute bout of exercise increased AMPK phosphorylation in all fibers ( P < 0.05), with the greatest increase occurring in type IIx fibers. Exercise training significantly increased basal AMPK phosphorylation in all fibers, and the exercise-induced increases were uniformly suppressed compared with pretraining exercise. Expression of AMPK-α1 and -α2 was similar between fibers and was not altered by exercise training. However, AMPK-γ3 was differentially expressed in skeletal muscle fibers (type IIx > type IIa > type I), irrespective of training status. Thus skeletal muscle AMPK phosphorylation and AMPK expression are fiber type specific in humans in the basal state, as well as during exercise. Our findings reveal fiber type-specific differences that have been masked in previous studies examining mixed muscle samples.
Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1receptors
Authors: Fu Liang-Wu , Longhurst John C.
Published: April 2009

Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (vlPAG), and rostral ventrolateral medulla (rVLM). Neurons in the ARC provide excitatory input to the vlPAG, whereas the vlPAG inhibits neuronal activity in the rVLM. γ-Aminobutyric acid (GABA) and glutamate (Glu) have been identified in the vlPAG. Endocannabinoids (ECs), acting as atypical neurotransmitters, inhibit the release of both neurotransmitters in the hypothalamus and midbrain through a presynaptic cannabinoid type 1 (CB1) receptor mechanism. The EC system has been observed in the dorsal but not in the vlPAG. Since it is uncertain whether ECs influence GABA and Glu in the vlPAG, the present study tested the hypothesis that EA modulates the release of these neurotransmitters in the vlPAG through a presynaptic CB1receptor mechanism. We measured the release of GABA and Glu simultaneously by using HPLC to assess samples collected with microdialysis probes inserted unilaterally into the vlPAG of intact anesthetized rats. Twenty-eight min of EA (2 Hz, 2–4 mA, 0.5 ms) at the P5–6 acupoints reduced the release of GABA by 39% during EA and by 44% 15 min after EA. Thirty-five minutes after EA, GABA concentrations returned to pre-EA levels. In contrast, sham EA did not change the vlPAG GABA concentration. Blockade of CB1receptors with AM251, a selective CB1receptor antagonist, reversed the EA-modulated changes in GABA concentration, whereas microinjection of vehicle into the vlPAG did not alter EA-modulated GABA changes. In addition, we observed no changes in the vlPAG Glu concentrations during EA, although the baseline concentration of Glu was much higher than that of GABA (3,541 ± 373 vs. 33.8 ± 8.7 nM, Glu vs. GABA). These results suggest that EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA, but not Glu, in the vlPAG, most likely through a presynaptic CB1receptor mechanism.
Gaussian-Process Factor Analysis for Low-Dimensional Single-Trial Analysis of Neural Population Activity
Authors: Yu Byron M. , Cunningham John P. , Santhanam Gopal , Ryu Stephen I. , Shenoy Krishna V. , Sahani Maneesh
Published: April 2009

We consider the problem of extracting smooth, low-dimensional neural trajectories that summarize the activity recorded simultaneously from many neurons on individual experimental trials. Beyond the benefit of visualizing the high-dimensional, noisy spiking activity in a compact form, such trajectories can offer insight into the dynamics of the neural circuitry underlying the recorded activity. Current methods for extracting neural trajectories involve a two-stage process: the spike trains are first smoothed over time, then a static dimensionality-reduction technique is applied. We first describe extensions of the two-stage methods that allow the degree of smoothing to be chosen in a principled way and that account for spiking variability, which may vary both across neurons and across time. We then present a novel method for extracting neural trajectories—Gaussian-process factor analysis (GPFA)—which unifies the smoothing and dimensionality-reduction operations in a common probabilistic framework. We applied these methods to the activity of 61 neurons recorded simultaneously in macaque premotor and motor cortices during reach planning and execution. By adopting a goodness-of-fit metric that measures how well the activity of each neuron can be predicted by all other recorded neurons, we found that the proposed extensions improved the predictive ability of the two-stage methods. The predictive ability was further improved by going to GPFA. From the extracted trajectories, we directly observed a convergence in neural state during motor planning, an effect that was shown indirectly by previous studies. We then show how such methods can be a powerful tool for relating the spiking activity across a neural population to the subject's behavior on a single-trial basis. Finally, to assess how well the proposed methods characterize neural population activity when the underlying time course is known, we performed simulations that revealed that GPFA performed tens of percent better than the best two-stage method.
An Avian Basal Ganglia-Forebrain Circuit Contributes Differentially to Syllable Versus Sequence Variability of Adult Bengalese Finch Song
Authors: Hampton Cara M. , Sakata Jon T. , Brainard Michael S.
Published: April 2009

Behavioral variability is important for motor skill learning but continues to be present and actively regulated even in well-learned behaviors. In adult songbirds, two types of song variability can persist and are modulated by social context: variability in syllable structure and variability in syllable sequencing. The degree to which the control of both types of adult variability is shared or distinct remains unknown. The output of a basal ganglia-forebrain circuit, LMAN (the lateral magnocellular nucleus of the anterior nidopallium), has been implicated in song variability. For example, in adult zebra finches, neurons in LMAN actively control the variability of syllable structure. It is unclear, however, whether LMAN contributes to variability in adult syllable sequencing because sequence variability in adult zebra finch song is minimal. In contrast, Bengalese finches retain variability in both syllable structure and syllable sequencing into adulthood. We analyzed the effects of LMAN lesions on the variability of syllable structure and sequencing and on the social modulation of these forms of variability in adult Bengalese finches. We found that lesions of LMAN significantly reduced the variability of syllable structure but not of syllable sequencing. We also found that LMAN lesions eliminated the social modulation of the variability of syllable structure but did not detect significant effects on the modulation of sequence variability. These results show that LMAN contributes differentially to syllable versus sequence variability of adult song and suggest that these forms of variability are regulated by distinct neural pathways.
Spike-Timing–Dependent Synaptic Plasticity and Synaptic Democracy in Dendrites
Authors: Gidon Albert , Segev Idan
Published: April 2009

We explored in a computational study the effect of dendrites on excitatory synapses undergoing spike-timing–dependent plasticity (STDP), using both cylindrical dendritic models and reconstructed dendritic trees. We show that even if the initial strength, gpeak, of distal synapses is augmented in a location independent manner, the efficacy of distal synapses diminishes following STDP and proximal synapses would eventually dominate. Indeed, proximal synapses always win over distal synapses following linear STDP rule, independent of the initial synaptic strength distribution in the dendritic tree. This effect is more pronounced as the dendritic cable length increases but it does not depend on the dendritic branching structure. Adding a small multiplicative component to the linear STDP rule, whereby already strong synapses tend to be less potentiated than depressed (and vice versa for weak synapses) did partially “save” distal synapses from “dying out.” Another successful strategy for balancing the efficacy of distal and proximal synapses following STDP is to increase the upper bound for the synaptic conductance ( gmax) with distance from the soma. We conclude by discussing an experiment for assessing which of these possible strategies might actually operate in dendrites.
A General Iterative Method for Solving the Variational Inequality Problem and Fixed Point Problem of an Infinite Family of Nonexpansive Mappings in Hilbert Spaces
Authors: Wangkeeree Rabian , Kamraksa Uthai
Published: April 2009

We introduce an iterative scheme for finding a common element of the set of common fixed points of a family of infinitely nonexpansive mappings, and the set of solutions of the variational inequality for an inverse-strongly monotone mapping in a Hilbert space. Under suitable conditions, some strong convergence theorems for approximating a common element of the above two sets are obtained. As applications, at the end of the paper we utilize our results to study the problem of finding a common element of the set of fixed points of a family of infinitely nonexpansive mappings and the set of fixed points of a finite family of "Equation missing"-strictly pseudocontractive mappings. The results presented in the paper improve some recent results of Qin and Cho (2008).
A First-Stage Approximation to Identify New Imprinted Genes through Sequence Analysis of Its Coding Regions
Authors: Daura-Oller Elias , Cabré Maria , Montero Miguel A. , Paternáin José L. , Romeu Antoni
Published: April 2009

In the present study, a positive training set of 30 known human imprinted gene coding regions are compared with a set of 72 randomly sampled human nonimprinted gene coding regions (negative training set) to identify genomic features common to human imprinted genes. The most important feature of the present work is its ability to use multivariate analysis to look at variation, at coding region DNA level, among imprinted and non-imprinted genes. There is a force affecting genomic parameters that appears through the use of the appropriate multivariate methods (principle components analysis (PCA) and quadratic discriminant analysis (QDA) to analyse quantitative genomic data. We show that variables, such as CG content, [bp]% CpG islands, [bp]% Large Tandem Repeats, and [bp]% Simple Repeats, are able to distinguish coding regions of human imprinted genes.
Optical and Multimodality Molecular Imaging
Authors: Jaffer Farouc A. , Libby Peter , Weissleder Ralph
Published: April 2009

Imaging approaches that visualize molecular targets rather than anatomic structures aim to illuminate vital molecular and cellular aspects of atherosclerosis biology in vivo. Several such molecular imaging strategies stand ready for rapid clinical application. This review describes the growing role of in vivo optical molecular imaging in atherosclerosis and highlights its ability to visualize atheroma inflammation, calcification, and angiogenesis. In addition, we discuss advances in multimodality probes, both in the context of multimodal imaging as well as multifunctional, or “theranostic,” nanoparticles. This review highlights particular molecular imaging strategies that possess strong potential for clinical translation.
Ion Channel Subunit Expression Changes in Cardiac Purkinje Fibers
Authors: Maguy Ange , Le Bouter Sabrina , Comtois Philippe , Chartier Denis , Villeneuve Louis , Wakili Reza , Nishida Kunihiro , Nattel Stanley
Published: April 2009

Purkinje fibers (PFs) play key roles in cardiac conduction and arrhythmogenesis. Congestive heart failure (CHF) causes well-characterized atrial and ventricular ion channel subunit expression changes, but effects on PF ion channel subunits are unknown. This study assessed changes in PF ion channel subunit expression (real-time PCR, immunoblot, immunohistochemistry), action potential properties, and conduction in dogs with ventricular tachypacing–induced CHF. CHF downregulated mRNA expression of subunits involved in action potential propagation (Nav1.5, by 56%; connexin [Cx]40, 66%; Cx43, 56%) and repolarization (Kv4.3, 43%, Kv3.4, 46%). No significant changes occurred in KChIP2, KvLQT1, ERG, or Kir3.1/3.4 mRNA. At the protein level, downregulation was seen for Nav1.5 (by 38%), Kv4.3 (42%), Kv3.4 (57%), Kir2.1 (26%), Cx40 (53%), and Cx43 (30%). Cx43 dephosphorylation was indicated by decreased larger molecular mass bands (pan-Cx43 antibody) and a 57% decrease in Ser368-phosphorylated Cx43 (phospho-specific antibody). Immunohistochemistry revealed reduced Cx40, Cx43, and phospho-Cx43 expression at intercalated disks. Action potential changes were consistent with observed decreases in ion channel subunits: CHF decreased phase 1 slope (by 56%), overshoot (by 32%), and phase 0 dV/dt
max
(by 35%). Impulse propagation was slowed in PF false tendons: conduction velocity decreased significantly from 2.2±0.1 m/s (control) to 1.5±0.1 m/s (CHF). His-Purkinje conduction also slowed in vivo, with HV interval increasing from 35.5±1.2 (control) to 49.3±3.4 ms (CHF). These results indicate important effects of CHF on PF ion channel subunit expression. Alterations in subunits governing conduction properties may be particularly important, because CHF-induced impairments in Purkinje tissue conduction, which this study is the first to describe, could contribute significantly to dyssynchronous ventricular activation, a major determinant of prognosis in CHF-patients.
Human Paraoxonase Gene Cluster Transgenic Overexpression Represses Atherogenesis and Promotes Atherosclerotic Plaque Stability in ApoE-Null Mice
Authors: She Zhi-Gang , Zheng Wei , Wei Yu-Sheng , Chen Hou-Zao , Wang Ai-Bing , Li Hong-Liang , Liu Guang , Zhang Ran , Liu Jin-Jing , Stallcup William B. , Zhou Zhongjun , Liu De-Pei , Liang Chih-Chuan
Published: April 2009

The paraoxonase (PON) gene cluster consists of the PON1, PON2, and PON3 genes, each of which can individually inhibit atherogenesis. To analyze the functions of the PON gene cluster (PC) in atherogenesis and plaque stability, human PC transgenic (Tg) mice were generated using bacterial artificial chromosome. The high-density lipoprotein from Tg mice exhibited increased paraoxonase activity. When crossed to the ApoE-null background and challenged by high-fat diet, PC Tg/ApoE-null mice formed significantly fewer atherosclerotic lesions. However overexpression of the PC transgene had no additive effect on atherosclerosis compared to the overexpression of the single PON1 or PON3 transgene. Plaques from PC Tg/ApoE-null mice exhibited increased levels of collagen and smooth muscle cells, and reduced levels of macrophages and lipid, compared with those from ApoE-null mice, indicating lesions of PC Tg/ApoE-null mice had characteristics of more stable plaques than those of ApoE-null mice. PC transgene enhanced high-density lipoprotein ability to protect low-density lipoprotein against oxidation in vitro. Serum intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 were also repressed by PC transgene. Proatherogenic reactions of Tg mouse peritoneal macrophages induced by oxidized low-density lipoprotein were inhibited by PC transgene, as indicated by reduced reactive oxygen species generation, inflammation, matrix metalloproteinase-9 expression, and foam cell formation. Our results demonstrate that the PC transgene not only represses atherogenesis but also promotes atherosclerotic plaque stability in vivo. PC may therefore be a useful target for atherosclerosis treatment.