bluuebunny/crossref_metadata_2025 huggingface dataset:
STABILITY OF RADIATIVE RELATIVISTIC SHOCKS TO GLOBAL OSCILLATIONS
Authors: KÖNIGL A. , GRANOT J.
Published: November 2008

Thermally emitting, radiative, Newtonian shocks exhibit a global oscillatory instability. The luminosity variations that accompany such oscillations raise the possibility that, if relativistic shocks that emit nonthermal (synchrotron and inverse-Compton) radiation are also subject to such an instability, this could be relevant to the interpretation of certain flares observed in relativistic jet sources associated with AGNs and GRBs. A linear stability analysis, using the equations of special-relativistic MHD and accounting for both the energy and the momentum carried by the radiation, has, however, revealed no unstable modes for physically plausible parameter values. The likely explanation is that, even though synchrotron cooling gives rise to a local radiative instability, the dependence on the magnetic field amplitude is not strong enough to counter the stabilizing effect of enhanced magnetic pressure, due to cooling-induced compression, on the global behavior of the shock. Numerical simulations are under way to ascertain that this conclusion continues to hold also in the nonlinear regime.
ENVIRONMENTAL LIMITS ON THE NONRESONANT COSMIC-RAY CURRENT-DRIVEN INSTABILITY
Authors: REVILLE B. , KIRK J. G. , DUFFY P. , O'SULLIVAN S.
Published: November 2008

We investigate the so-called nonresonant cosmic-ray streaming instability, first discussed by Bell (2004). The extent to which thermal damping and ion-neutral collisions reduce the growth of this instability is calculated. Limits on the growth of the nonresonant mode in SN1006 and RX J1713.7-3946 are presented.
WAVE TRANSMISSION AND HARD PARTICLE SPECTRA FROM PARALLEL SHOCKS
Authors: TAMMI JONI
Published: November 2008

I review recent results concerning the effects that relativistic parallel shocks can have on the particle-scattering turbulence, and how these effects, in turn, can change the shock's particle acceleration properties. I discuss the possibility of increased compression ratio due to this kind of turbulence transmission, and consider the effects of additional compression on the energy spectrum of the accelerated particles. Emphasis is put on the possibility of producing spectral indices that are significantly harder than what is usually expected from the first-order Fermi mechanism, but required by some observations. Finally, I discuss the physical requirements — and their plausibility in real astronomical objects — of this mechanism to have notable effects.
EFFECT OF RADIATIVE LOSSES ON PARTICLE ACCELERATION AT RELATIVISTIC SHOCKS
Authors: DEMPSEY PAUL , DUFFY PETER
Published: November 2008

We investigate the acceleration and simultaneous radiative losses of electrons in the vicinity of relativistic shocks. Particles undergo pitch angle diffusion, gaining energy as they cross the shock by the Fermi mechanism and also emitting synchrotron radiation in the ambient magnetic field. Using a semi-analytic approach we find that the cut-off energy differs greatly from the nonrelativistic approximation. Our results also show that, while low energy particles remain nearly isotropic, high energy particles downstream of the shock have a large degree of anisotropy which increases with the Lorentz factor of the shock. The implications for the synchrotron emission of relativistic jets, such as those in microquasars and blazars, are discussed.
A NEW MECHANISM FOR PARTICLE ACCELERATION IN RELATIVISTIC JETS
Authors: DERISHEV E. V. , AHARONIAN F. A. , KOCHAROVSKY V. V. , KOCHAROVSKY Vl. V.
Published: November 2008

We compare different acceleration mechanisms in application to relativistic jets and show that the converter mechanism, suggested recently, is the least sensitive to the geometry of the magnetic field in accelerators, and can routinely operate up to cosmic-ray energies close to the fundamental limit. The converter mechanism utilizes multiple conversions of charged particles into neutral ones (protons to neutrons and electrons/positrons to photons) and back by means of photon-induced reactions or inelastic nucleon-nucleon collisions. It works efficiently both in relativistic shocks and in shear flows under the conditions typical for active galactic nuclei, gamma-ray bursts, and microquasars, where it often outperforms the standard diffusive shock acceleration. The main advantages of the converter mechanism in such environments are that it greatly diminishes particle losses downstream and avoids the reduction in the energy gain factor, which normally takes place due to the highly collimated distribution of accelerated particles. We also discuss the properties of gamma-ray radiation, which accompanies acceleration of cosmic rays via the converter mechanism and can provide evidence for the latter. In particular, we point out that the opening angle of the radiation beam-pattern is different at different photon energies, which is relevant to the observability of gamma-ray sources as well as to their timing properties.
VHE GAMMA-RAYS FROM GALACTIC X-RAY BINARY SYSTEMS
Authors: PAREDES J. M.
Published: November 2008

The detection of TeV gamma-rays from LS 5039 and the binary pulsar PSR B1259–63 by HESS, and from LS I +61 303 and the stellar-mass black hole Cygnus X-1 by MAGIC, provides clear evidence of very efficient acceleration of particles to multi-TeV energies in X-ray binaries. These observations demonstrate the richness of nonthermal phenomena in compact galactic objects containing relativistic outflows or winds produced near black holes and neutron stars. I review here some of the main observational results on very high energy (VHE) γ-ray emission from X-ray binaries, as well as some of the proposed scenarios to explain the production of VHE γ-rays. I put special emphasis on the flare TeV emission, suggesting that the flaring activity might be a common phenomena in X-ray binaries.
CONFIRMING THE ORBITAL X-RAY VARIABILITY OF LS 5039 THROUGH CHANDRA OBSERVATIONS
Authors: ZABALZA V. , PAREDES J. M. , BOSCH-RAMON V.
Published: November 2008

We present an analysis of two Chandra observations of LS 5039 performed in 2004 in two different orbital phases during the same orbital cycle. Our results show a clear flux variability, confirming a trend of increasing flux with orbital phase in the range 0.05 ≲ ϕ ≲ 0.7 as has been found in XMM observations carried out in 2005 during the same orbital cycle. We suggest that the X-ray variations are linked to orbital changes of the intrinsic properties of the emitter, which should have implications for possible emission models to explain the present multiwavelength knowledge of the source.
ON THE X-RAY/TEV CONNECTION IN GALACTIC JET SOURCES
Authors: BOSCH-RAMON V. , KHANGULYAN D. V. , AHARONIAN F. A.
Published: November 2008

There are three Galactic jet sources from which TeV emission has been detected: LS 5039, LS I +61 303 and Cygnus X-1. These three sources show power-law tails in X-rays and soft gamma-rays that could indicate a nonthermal origin of this radiation. In addition, all three sources apparently show correlated and complex behavior at X-ray and TeV energies. In some cases, this complex behavior is related to the orbital motion (e.g. LS 5039, LS I +61 303), and in some others it is related to some transient events occurring in the system (e.g. Cygnus X-1, and likely also LS I +61 303 and LS 5039). Based on modeling results or on energetic grounds, it seems difficult to explain the emission in the X-/soft gamma-ray and the TeV bands as coming from the same (i.e. one-zone) region. We also stress the importance of the pair creation phenomena in these systems, which harbor a massive and hot star, for the radio and the X-ray emission, as a secondary pair radiation component may be significant in these energy ranges. Finally, we point out that the presence of the star can indeed have a strong impact on both the nonthermal radiation production and the jet dynamics.
MODELS FOR GAMMA-RAY PRODUCTION IN LOW-MASS MICROQUASARS
Authors: VILA G. S. , ROMERO G. E.
Published: November 2008

Unlike high-mass gamma-ray binaries, low-mass microquasars lack external sources of radiation and matter that could produce high-energy emission through interactions with relativistic particles. In this work, we consider the synchrotron emission of protons and leptons that populate the jet of a low-mass microquasar. In our model photohadronic and inverse Compton (IC) interactions with synchrotron photons produced by both protons and leptons result in a high-energy tail of the spectrum. We also estimate the contribution from secondary pairs injected through photopair production. The high-energy emission is dominated by radiation of hadronic origin, so we can call these objects "proton microquasars".
HYDRODYNAMICS OF INTERACTION OF PULSAR AND STELLAR WINDS AND ITS IMPACT ON THE HIGH ENERGY RADIATION OF BINARY PULSAR SYSTEMS
Authors: KHANGULYAN D. V. , AHARONIAN F. A. , BOGOVALOV S. V. , KOLDOBA A. V. , USTYUGOVA G. V.
Published: November 2008

The hydrodynamics of the interaction of pulsar and stellar winds in binary systems harboring a pulsar and its impact on the nonthermal radiation of the binary pulsar PSR B1259-63/SS2883 is discussed. The collision of an ultrarelativistic pulsar wind with a nonrelativistic stellar outflow results in significant bulk acceleration of the shocked material from the pulsar wind. Already at distances comparable to the size of the binary system, the Lorentz factor of the shocked flow can be as large as γ ~ 4. This results in significant anisotropy of the inverse Compton radiation of accelerated electrons. Because of the Doppler boosting of the produced radiation, one should expect a variable gamma-ray signal from the system. In particular, this effect may naturally explain the reported tendency of a decrease of TeV gamma-ray flux close to the periastron. The modeling of the interaction of pulsar and stellar winds allows self-consistent calculations of adiabatic losses. Our results show that adiabatic losses dominate over the radiative losses. These results have direct impact on the orbital variability of radio, X-ray and gamma-ray signals detected from the binary pulsar PSR B1259-63/SS2883.
MODELING THE SS 433 JET BENDS
Authors: MARSHALL H. L. , CANIZARES CLAUDE R. , SCHULZ NORBERT S. , HEINZ SEBASTIAN , HILLWIG TODD C. , MIODUSZEWSKI AMY J.
Published: November 2008

We fit Chandra HETGS data obtained for the unusual X-ray binary SS 433. While line strengths and continuum levels hardly change, the jet Doppler shifts show aperiodic variations that probably result from shocks in interactions with the local environment. The X-ray and optical emission line regions are found to be related but not coincident as the optical line emission persists for days while the X-ray emission lines fade in less than 5000 s. The X-ray spectrum of the blueshifted jet shows over two dozen emission lines from plasma at a variety of temperatures. The emission measure distribution derived from the spectrum can be used to test jet cooling models.
JET FORMATION IN MICROQUASARS AND ACTIVE GALACTIC NUCLEI: MAGNETIC FIELD LIMITS
Authors: KAUFMAN BERNADÓ M. M. , MASSI M.
Published: November 2008

We introduce the use of a well-known parameter, the Alfvén Radius, R A , as a new tool to discern whether an X-ray binary system may undergo a microquasar phase, i.e. ejecting relativistic particles orthogonal to the accretion disk. We study what we call the basic condition, R A /R* = 1 in its dependency on the magnetic field strength and the mass accretion rate. With this basic condition we establish under which combination of parameters any class of accreting neutron stars could become a microquasar instead of confining disk-material down to the magnetic poles and creating the two emitting caps typical for an X-ray pulsar. In the case of black-hole accreting binaries we equate the magnetic field pressure to the plasma pressure in the last stable orbit (i.e. R A /R LSO = 1) and we get upper limits for the magnetic field strength as a function of the mass accretion rate and the black hole mass.
STUDYING THE INTERACTION BETWEEN MICROQUASAR JETS AND THEIR ENVIRONMENTS
Authors: PERUCHO M. , BOSCH-RAMON V.
Published: November 2008

In high-mass microquasars (HMMQ), strong interactions between jets and stellar winds at binary system scales could occur. In order to explore this possibility, we have performed numerical two-dimensional hydrodynamical simulations of jets crossing the dense stellar material to study how the jet will be affected by these interactions. We find that the jet head generates strong shocks in the wind. These shocks reduce the jet advance speed, and compress and heat up the jet and wind material. In addition, strong recollimation shocks can occur where pressure balance between the jet side and the surrounding medium is reached. All this, together with jet bending, could lead to the destruction of jets with power < 1036 erg/s . The conditions around the outflow shocks would be convenient for accelerating particles up to ~ TeV energies. These accelerated particles could emit via synchrotron and inverse Compton (IC) scattering if they were leptons, and via hadronic processes if they were hadrons.
PULSED HIGH-ENERGY EMISSION AND PHASE-RESOLVED SPECTRA BY INVERSE COMPTON SCATTERING IN A PULSAR STRIPED WIND
Authors: PÉTRI JÉRÔME , KIRK JOHN G.
Published: November 2008

To date, seven gamma-ray pulsars are known, showing pulsed emission up to tens of GeV and associated light-curves with a double-pulse structure. We study this pulsed high-energy emission in the framework of the striped wind model. By numerical integration of the time-dependent emissivity in the current sheets, we compute the phase-dependent spectral variability of the inverse Compton radiation. Several light curves and spectra are presented. The pulses are a direct consequence of relativistic beaming. Our model is able to explain some of the high-energy (10 MeV–10 GeV) spectral features and behavior of several gamma-ray pulsars, such as Geminga and Vela.
THE COUPLED NATURAL BOUNDARY-FINITE ELEMENT METHOD FOR SOLVING THE ACOUSTIC SCATTERING PROBLEM IN A 3D OCEANIC WAVEGUIDE
Authors: PAN WENFENG , LI ZHUOQIU
Published: November 2008

This study is concerned with the problem of acoustic scattering by a three-dimensional obstacle in a shallow water waveguide. A method coupling of the finite-element and natural boundary-element is analyzed and presented for solving the acoustic scattering problem numerically based on the Galerkin variational principle and the DtN mapping theory. The proposed method has the advantage of avoiding the absorbing boundary condition of the conventional finite-element method. Numerical examples are given of successful computational results for several 3D obstacles of various shapes.
A NEUMANN TO DIRICHLET MAP FOR THE BOTTOM BOUNDARY OF A STRATIFIED SUB-BOTTOM REGION IN PARABOLIC APPROXIMATION
Authors: PAPADAKIS JOHN S. , FLOURI EVANGELIA T.
Published: November 2008

The acoustic propagation problem is modeled via the parabolic approximation. The physical domain consists of the water column with a horizontal water–bottom interface and the bottom region consists of N-strata with horizontal interfaces. The computational domain is restricted to the water column, while the stratified bottom region is modeled by a nonlocal boundary condition applied along the water–bottom interface, and having the form of a Neumann to Dirichlet map (NtD). The discrete analog of the NtD has been implemented in a finite difference scheme for the general wide angle PE model, and successfully tested for several benchmark problems. The stratification of the media can be either physical, e.g. sediment formulation in the bottom, or artificial/computational, e.g. forced by sparse distribution of environmental data measurements in the water column. It should be emphasized that the sound speed may vary from layer to layer, but is constant within each layer. The proposed NtD map can be used in geoacoustic inversion via the optimal control adjoint method.
NUMERICAL COMPUTATION OF THE SOUND RADIATION FROM A PLANAR BAFFLED VIBRATING SURFACE
Authors: ARENAS JORGE P.
Published: November 2008

The sound power radiated by a plane vibrating structure can be calculated by numerical integration of the Rayleigh integral or by means of finite and boundary element methods. However, these methods are usually time-consuming due to the numerical evaluation of surface integrals. This paper reviews and discusses an alternative numerical method (the lumped parameter model) to compute the sound radiation from planar structures which is based just on surface velocity information and a direct numerical evaluation of the radiation resistance matrix of the structure. As an example, the technique is applied to estimate the sound radiated from the structural axisymmetric modes of both clamped and simply-supported circular baffled plates.
A FINITE DIFFERENCE SOLUTION TO THE HELMHOLTZ EQUATION IN A RADIALLY SYMMETRIC WAVEGUIDE: APPLICATION TO NEAR-SOURCE SCATTERING IN OCEAN ACOUSTICS
Authors: DE GROOT-HEDLIN CATHERINE
Published: November 2008

A finite difference (FD) method is developed and analyzed for the Helmholtz equation in a radially symmetric waveguide. The resulting algorithm can be used to solve for sound intensities in complex models that may include high material contrasts and arbitrary bathymetry. An analysis of the effect of grid discretization on the results indicates that numerical dispersion is significant within one-third of a wavelength from a point source and decreases beyond that. Numerical results are presented and compared to wide-angle parabolic equation (PE) solutions and analytic solutions, where available. Comparison with analytic results indicates that the FD method accurately solves for the acoustic wave field at all propagation angles and is more accurate than the PE method near the source. Results are also shown for models in which mode coupling occurs near the source.
Quantitative Genomics: Analyzing Intraspecific Variation Using Global Gene Expression Polymorphisms or eQTLs
Authors: Kliebenstein Dan
Published: November 2008

Scientific inquiries in fields ranging from ecology to plant breeding assess phenotypic variation within a plant species either to explain its presence or utilize its consequences. Frequently this natural genetic variation is studied via mapping quantitative trait loci (QTLs); however, elucidation of the underlying molecular mechanisms is a continuing bottleneck. The genomic analysis of transcripts as individual phenotypes has led to the emerging field of expression QTL analysis. This field has begun both to delve into the ecological/evolutionary significance of this transcript variation as well as to use specific eQTLs to speed up our analysis of the molecular basis of quantitative traits. This review introduces eQTL analysis and begins to illustrate how these data can be applied to multiple research fields.
Health Effects of Arsenic and Chromium in Drinking Water: Recent Human Findings
Authors: Smith Allan H. , Steinmaus Craig M.
Published: November 2008

Even at high concentrations, arsenic-contaminated water is translucent, tasteless, and odorless. Yet almost every day, studies report a continually increasing plethora of toxic effects that have manifested in exposed populations throughout the world. In this article we focus on recent findings, in particular those associated with major contributions since 2006. Early life exposure, both in utero and in childhood, has been receiving increased attention, and remarkable increases in consequent mortality in young adults have been reported. New studies address the dose-response relationship between drinking-water arsenic concentrations and skin lesions, and new findings have emerged concerning arsenic and cardiovascular disease. We also review the increasing epidemiological evidence that the first step of methylation of inorganic arsenic to monomethylated arsenic (MMA) is actually an activation step rather than the first step in detoxification, as once thought. Hexavalent chromium differs from arsenic in that it discolors water, turning the water yellow at high concentrations. A controversial issue is whether chromium causes cancer when ingested. A recent publication supports the original findings in China of increased cancer mortality in a population where well water turned yellow with chromium.
GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit
Authors: Herman Melissa A. , Cruz Maureen T. , Sahibzada Niaz , Verbalis Joseph , Gillis Richard A.
Published: November 2008

It has been proposed that there is an “apparent monosynaptic” connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes ( 6 ). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release l-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABAAreceptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (−1.6 ± 0.2 mmHg, P < 0.05, n = 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABAAreceptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or NG-nitro-l-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABAAreceptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABAAreceptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit.
Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration
Authors: Knuth Nicolas D. , Shrivastava Cara R. , Horowitz Jeffrey F.
Published: November 2008

The primary goal of this study was to determine the acute glycemic and endocrine responses to the reduction of fat content from a meal. On three separate occasions, nine overweight subjects (body mass index = 30 ± 1 kg/m2; 5 men, 4 women) consumed 1) a control meal (∼800 kcal; 100 g of carbohydrate, 31 g of fat, and 30 g of protein), 2) a low-fat meal (∼530 kcal; 100 g of carbohydrate, 1 g of fat, and 30 g of protein), or 3) a low-fat meal plus lipid infusion [same meal as low-fat meal, but the total energy provided was the same as control (800 kcal), with the “missing” fat (∼30 g) provided via an intravenous lipid infusion]. All three meals contained [13C]glucose (3 mg/kg body wt) to assess the bioavailability of ingested glucose. During the 5-h period after each meal, we measured the recovery of [13C]glucose in plasma, plasma glucose, and insulin concentrations. We also measured plasma concentration of the gastrointestinal peptides: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY3-36(PYY3-36). The recovery of the ingested [13C]glucose in the hour after ingestion was greater ( P < 0.05) after the low-fat than after the control meal [area under the curve (AUC): 1,206 ± 252 and 687 ± 161 μM·h, respectively]. However, removing dietary fat from the meal did not affect the plasma concentration of glucose or insulin. Importantly, [13C]glucose recovery was not different during the low-fat and lipid infusion trials (AUC: 1,206 ± 252 and 1,134 ± 247 μM·h, respectively), indicating that the accelerated delivery of exogenous glucose found after removing fat from the meal is due exclusively to the reduction of fat in the gastrointestinal tract. In parallel with these findings, the reduction in fat calories from the meal reduced plasma concentration of GIP, GLP-1, and PYY3-36. In summary, these data suggest that removing fat from the diet expedited exogenous glucose delivery into the systemic circulation and reduced the concentration of key gastrointestinal peptides, yet maintained plasma glucose concentration at control levels.
Variations within oxygen-regulated gene expression in humans
Authors: Brooks Jerome T. S. , Elvidge Gareth P. , Glenny Louisa , Gleadle Jonathan M. , Liu Chun , Ragoussis Jiannis , Smith Thomas G. , Talbot Nick P. , Winchester Laura , Maxwell Patrick H. , Robbins Peter A.
Published: November 2008

The effects of hypoxia on gene transcription are mainly mediated by a transcription factor complex termed hypoxia-inducible factor (HIF). Genetic manipulation of animals and studies of humans with rare hereditary disease have shown that modifying the HIF pathway affects systems-level physiological responses to hypoxia. It is, however, an open question whether variations in systems-level responses to hypoxia between individuals could arise from variations within the HIF system. This study sought to determine whether variations in the responsiveness of the HIF system at the cellular level could be detected between normal individuals. Peripheral blood lymphocytes (PBL) were isolated on three separate occasions from each of 10 healthy volunteers. After exposure of PBL to eight different oxygen tensions ranging from 20% to 0.1%, the expression levels of four HIF-regulated transcripts involved in different biological pathways were measured. The profile of expression of all four transcripts in PBL was related to oxygen tension in a curvilinear manner. Double logarithmic transformation of these data resulted in a linear relationship that allowed the response to be parameterized through a gradient and intercept. Analysis of variance (ANOVA) on these parameters showed that the level of between-subject variation in the gradients of the responses that was common across all four HIF-regulated transcripts was significant ( P = 0.008). We conclude that statistically significant variation within the cellular response to hypoxia can be detected between normal humans. The common nature of the variability across all four HIF-regulated genes suggests that the source of this variation resides within the HIF system itself.
Image-based finite element modeling of alveolar epithelial cell injury during airway reopening
Authors: Dailey H. L. , Ricles L. M. , Yalcin H. C. , Ghadiali S. N.
Published: November 2008

The acute respiratory distress syndrome (ARDS) is characterized by fluid accumulation in small pulmonary airways. The reopening of these fluid-filled airways involves the propagation of an air-liquid interface that exerts injurious hydrodynamic stresses on the epithelial cells (EpC) lining the airway walls. Previous experimental studies have demonstrated that these hydrodynamic stresses may cause rupture of the plasma membrane (i.e., cell necrosis) and have postulated that cell morphology plays a role in cell death. However, direct experimental measurement of stress and strain within the cell is intractable, and limited data are available on the mechanical response (i.e., deformation) of the epithelium during airway reopening. The goal of this study is to use image-based finite element models of cell deformation during airway reopening to investigate how cell morphology and mechanics influence the risk of cell injury/necrosis. Confocal microscopy images of EpC in subconfluent and confluent monolayers were used to generate morphologically accurate three-dimensional finite element models. Hydrodynamic stresses on the cells were calculated from boundary element solutions of bubble propagation in a fluid-filled parallel-plate flow channel. Results indicate that for equivalent cell mechanical properties and hydrodynamic load conditions, subconfluent cells develop higher membrane strains than confluent cells. Strain magnitudes were also found to decrease with increasing stiffness of the cell and membrane/cortex region but were most sensitive to changes in the cell's interior stiffness. These models may be useful in identifying pharmacological treatments that mitigate cell injury during airway reopening by altering specific biomechanical properties of the EpC.
Algorithm for transient response of whole body indirect calorimeter: deconvolution with a regularization parameter
Authors: Tokuyama Kumpei , Ogata Hitomi , Katayose Yasuko , Satoh Makoto
Published: November 2008

A whole body indirect calorimeter provides accurate measurement of energy expenditure over long periods of time, but it has limitations to assess its dynamic changes. The present study aimed to improve algorithms to compute O2 consumption and CO2 production by adopting a stochastic deconvolution method, which controls the relative weight of fidelity to the data and smoothness of the estimates. The performance of the new algorithm was compared with that of other algorithms (moving average, trends identification, Kalman filter, and Kalman smoothing) against validation tests in which energy metabolism was evaluated every 1 min. First, an in silico simulation study, rectangular or sinusoidal inputs of gradually decreasing periods (64, 32, 16, and 8 min) were applied, and samples collected from the output were corrupted with superimposed noise. Second, CO2 was infused into a chamber in gradually decreasing intervals and the CO2 production rate was estimated by algorithms. In terms of recovery, mean square error, and correlation to the known input signal in the validation tests, deconvolution performed better than the other algorithms. Finally, as a case study, the time course of energy metabolism during sleep, the stages of which were assessed by a standard polysomnogram, was measured in a whole body indirect calorimeter. Analysis of covariance revealed an association of energy expenditure with sleep stage, and energy expenditure computed by deconvolution and Kalman smoothing was more closely associated with sleep stages than that based on trends identification and the Kalman filter. The new algorithm significantly improved the transient response of the whole body indirect calorimeter.
High-frequency submaximal stimulation over muscle evokes centrally generated forces in human upper limb skeletal muscles
Authors: Blouin Jean-Sébastien , Walsh Lee D. , Nickolls Peter , Gandevia Simon C.
Published: November 2008

Control of posture and movement requires control of the output from motoneurons. Motoneurons of human lower limb muscles exhibit sustained, submaximal activity to high-frequency electrical trains, which has been hypothesized to be partly triggered by monosynaptic Ia afferents. The possibility to trigger such behavior in upper limb motoneurons and the potential unique role of Ia afferents to trigger such behavior remain unclear. Subjects ( n = 9) received high-frequency trains of electrical stimuli over biceps brachii and flexor pollicis longus (FPL). We chose to study the FPL muscle because it has weak monosynaptic Ia afferent connectivity and it is involved in fine motor control of the thumb. Two types of stimulus trains (100-Hz bursts and triangular ramps) were tested at five intensities below painful levels. All subjects exhibited enhanced torque in biceps and FPL muscles after both types of high-frequency train. Torques also persisted after stimulation, particularly for the highest stimulus intensity. To separate the evoked torques that resulted from a peripheral mechanism (e.g., muscle potentiation) and that which resulted from a central origin, we studied FPL responses to high-frequency trains after complete combined nerve blocks of the median and radial nerves ( n = 2). During the blocks, high-frequency trains over the FPL did not yield torque enhancements or persisting torques. These results suggest that enhanced contractions of central origin can be elicited in motoneurons innervating the upper limb, despite weak monosynaptic Ia connections for FPL. Their presence in a recently evolved human muscle (FPL) indicates that these enhanced contractions may have a broad role in controlling tonic postural outputs of hand muscles and that they may be available even for fine motor activities involving the thumb.
Pulmonary gas exchange in diving
Authors: Moon R. E. , Cherry A. D. , Stolp B. W. , Camporesi E. M.
Published: November 2008

Diving-related pulmonary effects are due mostly to increased gas density, immersion-related increase in pulmonary blood volume, and (usually) a higher inspired Po2. Higher gas density produces an increase in airways resistance and work of breathing, and a reduced maximum breathing capacity. An additional mechanical load is due to immersion, which can impose a static transrespiratory pressure load as well as a decrease in pulmonary compliance. The combination of resistive and elastic loads is largely responsible for the reduction in ventilation during underwater exercise. Additionally, there is a density-related increase in dead space/tidal volume ratio (Vd/Vt), possibly due to impairment of intrapulmonary gas phase diffusion and distribution of ventilation. The net result of relative hypoventilation and increased Vd/Vt is hypercapnia. The effect of high inspired Po2and inert gas narcosis on respiratory drive appear to be minimal. Exchange of oxygen by the lung is not impaired, at least up to a gas density of 25 g/l. There are few effects of pressure per se, other than a reduction in the P50 of hemoglobin, probably due to either a conformational change or an effect of inert gas binding.
Killer Dendritic Cells Link Innate and Adaptive Immunity against Established Osteosarcoma in Rats
Authors: Chauvin Camille , Philippeau Jean-Marie , Hémont Caroline , Hubert Francois-Xavier , Wittrant Yohann , Lamoureux Francois , Trinité Benjamin , Heymann Dominique , Rédini Françoise , Josien Régis
Published: November 2008

We have previously reported that a distinct subset of splenic CD4− rat dendritic cells (DC) induces a rapid and caspase-independent apoptosis-like cell death in a large number of tumor cells in vitro. The killing activity of these killer DC (KDC) was restricted to their immature state and was immediately followed by their engulfment of the apoptotic target cells, suggesting that these KDC could directly link innate and adaptive immunity to tumors. Here, we addressed this question using a transplantable model of rat osteosarcoma. First, we showed that rat KDC have an MHC II+CD103+CD11b+NKp46− phenotype and are therefore distinct from natural killer cells, which are MHC II−CD103−CD11b−NKp46+. KDC numbers could be specifically and strongly (up to 10-fold) enhanced by Flt3L in vivo. The OSRGa cell line derived from the osteosarcoma tumor was killed and phagocytosed in vitro by both normal and Flt3L-induced splenic KDC. Such tumor antigen–loaded KDC were used to s.c. vaccinate progressive tumor-bearing rats. Vaccination with OSRGa-loaded KDC but not KDC loaded with irrelevant tumor cells (Jurkat) delayed tumor progression or even induced tumor regression. This vaccine effect was not observed in CD8 T cell–depleted animals and protective against tumor rechallenge. These results suggest that KDC possess the intrinsic capability not only to kill and then engulf tumor cells but also to efficiently cross-present tumor cell–derived antigen in vivo and subsequently induce an adaptive antitumor immune response. [Cancer Res 2008;68(22):9433–40]
Interplay between the Nuclear Receptor Pregnane X Receptor and the Uptake Transporter Organic Anion Transporter Polypeptide 1A2 Selectively Enhances Estrogen Effects in Breast Cancer
Authors: Meyer zu Schwabedissen Henriette E. , Tirona Rommel G. , Yip Cindy S. , Ho Richard H. , Kim Richard B.
Published: November 2008

The ligand-activated nuclear receptor pregnane X receptor (PXR) is known to play a role in the regulated expression of drug metabolizing enzymes and transporters. Recent studies suggest a potential clinically relevant role of PXR in breast cancer. However, the relevant pathway or target genes of PXR in breast cancer biology and progression have not yet been fully clarified. In this study, we show that mRNA expression of organic anion transporter polypeptide 1A2 (OATP1A2), a transporter capable of mediating the cellular uptake of estrogen metabolites, is nearly 10-fold greater in breast cancer compared with adjacent healthy breast tissues. Immunohistochemistry revealed exclusive expression of OATP1A2 in breast cancer tissue. Interestingly, treatment of breast cancer cells in vitro with the PXR agonist rifampin induced OATP1A2 expression in a time-dependent and concentration-dependent manner. Consistent with its role as a hormone uptake transporter, induction of OATP1A2 was associated with increased uptake of estrone 3-sulfate. The rifampin response was abrogated after small interfering RNA targeting of PXR. We then identified a PXR response element in the human OATP1A2 promoter, located ∼5.7 kb upstream of the transcription initiation site. The specificity of PXR-OATP1A2 promoter interaction was confirmed using chromatin immunoprecipitation. Importantly, we used a novel potent and specific antagonist of PXR (A-792611) to show the reversal of the rifampin effect on the cellular uptake of E1S. These data provide important new insights into the interplay between a xenobiotic nuclear receptor PXR and OATP1A2 that could contribute to the pathogenesis of breast cancer and may also prove to be heretofore unrecognized targets for breast cancer treatment. [Cancer Res 2008;68(22):9338–47]
Effect of Fenretinide and Low-Dose Tamoxifen on Insulin Sensitivity in Premenopausal Women at High Risk for Breast Cancer
Authors: Johansson Harriet , Gandini Sara , Guerrieri-Gonzaga Aliana , Iodice Simona , Ruscica Massimiliano , Bonanni Bernardo , Gulisano Marcella , Magni Paolo , Formelli Franca , Decensi Andrea
Published: November 2008

The prevalence of metabolic syndrome is increasing along with breast cancer incidence worldwide. Because fenretinide improves insulin action and glucose tolerance in insulin-resistant obese mice and because tamoxifen has shown to regulate several markers involved in metabolic syndrome, we sought to investigate the effect of fenretinide or tamoxifen at low dose on features linked to insulin resistance in premenopausal women at risk for breast cancer. We randomized 235 women to low-dose tamoxifen (5 mg/daily), fenretinide (200 mg/daily), or their combination or placebo for 2 years. We used the homeostasis model assessment (HOMA; fasting insulin × glucose/22.5) to estimate insulin sensitivity. Women were considered to improve insulin sensitivity when they shifted from a HOMA ≥2.8 to <2.8. There was no effect of fenretinide or tamoxifen on HOMA overall, but overweight women (body mass index, ≥25 kg/m2) had a 7-fold greater probability to normalize HOMA after 2 years of fenretinide treatment [odds ratio (OR), 7.0; 95% confidence interval (95% CI), 1.2–40.5], with 25% of women improving their insulin sensitivity, whereas tamoxifen decreased insulin sensitivity by almost 7 times compared with subjects not taking tamoxifen (OR, 0.15; 95% CI, 0.03–0.88). In this group only, 5% improved their insulin sensitivity. Interestingly, women with intraepithelial or microinvasive neoplasia had higher HOMA (3.0) than unaffected subjects (2.8; P = 0.07). Fenretinide can positively balance the metabolic profile in overweight premenopausal women and this may favorably affect breast cancer risk. Furthermore, features of the metabolic syndrome should be taken into consideration before proposing tamoxifen for breast cancer prevention. The clinical implications of these results require further investigations. [Cancer Res 2008;68(22):9512–8]
Does the Renin-Angiotensin System Participate in Regulation of Human Vasculogenesis and Angiogenesis?
Authors: Khakoo Aarif Y. , Sidman Richard L. , Pasqualini Renata , Arap Wadih
Published: November 2008

Several lines of evidence suggest that hypertension and angiogenesis may be related phenomena but a functional link remains elusive. Here, we propose that the renin-angiotensin system (RAS), in addition to its central role in arterial hypertension, also regulates blood vessel formation during normal development and cancer. This mechanistic hypothesis is based on reports of biochemical, genetic, clinical, and epidemiologic data reviewed herein. Species differences between the RAS of rodents and humans likely account for why such a fundamental role in angiogenesis went unrecognized for so long. If proven correct, this hypothesis carries many implications for the medical practices of cardiology, oncology, and neonatology. [Cancer Res 2008;68(22):9112–5]
The Mitogen-Activated Protein Kinase Phosphatase Vaccinia H1–Related Protein Inhibits Apoptosis in Prostate Cancer Cells and Is Overexpressed in Prostate Cancer
Authors: Arnoldussen Yke Jildouw , Lorenzo Petra I. , Pretorius Maria E. , Wæhre Håkon , Risberg Bjørn , Mælandsmo Gunhild M. , Danielsen Håvard E. , Saatcioglu Fahri
Published: November 2008

Androgen ablation during the initial stages of prostate cancer causes regression of the tumor due to an increase in apoptosis and reduced cellular proliferation. However, prostate cancer invariably progresses to an androgen-independent state for poorly understood reasons. Previous studies showed that c-Jun NH2 terminal kinase (JNK) is required for 12-O-tetradecanoylphorbol-13-acetate (TPA)– and thapsigargin (TG)–induced apoptosis in the androgen-responsive prostate cancer cell line LNCaP. Androgens protect LNCaP cells from TPA-induced or TG-induced apoptosis via down-regulation of JNK activation. However, the molecular mechanisms of this inhibition are not clear. Here, we systematically investigated the possible regulation of mitogen-activated protein kinase phosphatases/dual-specificity phosphatases during apoptosis of LNCaP cells and found that Vaccinia H1–related protein (VHR/DUSP3) is up-regulated by androgens during inhibition of apoptosis in LNCaP cells, but not in androgen-independent DU145 cells. Ectopic expression of wild-type VHR, but not a catalytically inactive mutant, interfered with TPA- and TG-induced apoptosis. Consistently, small interfering RNA–mediated knockdown of endogenous VHR increased apoptosis in response to TPA or TG in the presence of androgens. Furthermore, COS7 cells stably expressing wild-type VHR, but not a mutant, had a decrease in JNK phosphorylation. In vivo, VHR expression decreased in the androgen-dependent human prostate cancer xenograft CWR22 upon androgen withdrawal and was inversely correlated to JNK phosphorylation. Expression analysis in human prostate cancer specimens showed that VHR is increased in prostate cancer compared with normal prostate. These data show that VHR has a direct role in the inhibition of JNK-dependent apoptosis in LNCaP cells and may therefore have a role in prostate cancer progression. [Cancer Res 2008;68(22):9255–64]
Angiotensin II Induces DNA Damage in the Kidney
Authors: Schmid Ursula , Stopper Helga , Schweda Frank , Queisser Nina , Schupp Nicole
Published: November 2008

Increased activity of the renin angiotensin system with enhanced levels of angiotensin II leads to oxidative stress with endothelial dysfunction, hypertension, and atherosclerosis. Epidemiologic studies revealed a higher cancer mortality and an increased kidney cancer incidence in hypertensive patients. Because elevated angiotensin II levels might contribute to carcinogenesis, we tested whether angiotensin II induces DNA damage in the kidney. In isolated perfused mouse kidneys, as little as 1 nmol/L angiotensin II caused a significant increase in DNA strand breaks, measured with the comet assay. This damage was independent of the hemodynamic effect of angiotensin II and mediated by the angiotensin II type 1 receptor. Angiotensin II also caused double-strand breaks in the cells of the isolated perfused kidney, detected with an antibody against the double-strand break marker γ-H2AX. Studies in cell culture allowed further characterization of the DNA damage induced by angiotensin II. Single- and double-strand breaks, abasic sites, and 7,8-dihydro-8-oxo-guanine, all types of oxidative DNA lesions, were detected in angiotensin II–treated renal cells. The majority of detected strand breaks was repaired within 1 hour, but double-strand breaks increased and persisted for at least 24 hours. [Cancer Res 2008;68(22):9239–46]
Evidence for an Important Role of CIDEA in Human Cancer Cachexia
Authors: Laurencikiene Jurga , Stenson Britta M. , Arvidsson Nordström Elisabet , Agustsson Thorhallur , Langin Dominique , Isaksson Bengt , Permert Johan , Rydén Mikael , Arner Peter
Published: November 2008

Loss of fat mass in cancer cachexia is linked to increased adipocyte lipolysis; however, the fate of the excess fatty acids (FA) generated by lipolysis is not known. We investigated if the adipocyte-specific gene cell death–inducing DNA fragmentation factor-α–like effector A (CIDEA) could be involved. CIDEA mRNA expression was assessed in s.c. white adipose tissue from 23 cancer cachexia patients, 17 weight-stable cancer patients, and 8 noncancer patients. CIDEA was also overexpressed in adipocytes in vitro. CIDEA expression was increased in cancer cachexia (P < 0.05) and correlated with elevated levels of FAs and reported weight loss (P < 0.001). CIDEA overexpression in vitro increased FA oxidation 2- to 4-fold (P < 0.01), decreased glucose oxidation by 40% (P < 0.01), increased the expression of pyruvate dehydrogenase kinase (PDK) 1 and PDK4 (P < 0.01), and enhanced the phosphorylation (inactivation) of the pyruvate dehydrogenase complex (PDC). Inactivation of PDC facilitates FA oxidation by favoring the metabolism of FAs over glucose to acetyl-CoA. In accordance with the in vitro data, PDK1 and PDK4 expression correlated strongly with CIDEA expression in white adipose tissue (P < 0.001). We conclude that CIDEA is involved in adipose tissue loss in cancer cachexia and this may, at least in part, be due to its ability to inactivate PDC, thereby switching substrate oxidation in human fat cells from glucose to FAs. [Cancer Res 2008;68(22):9247–54]
IκBα Kinase Inhibitor IKI-1 Conferred Tumor Necrosis Factor α Sensitivity to Pancreatic Cancer Cells and a Xenograft Tumor Model
Authors: Zhang Yixian , Gavriil Maria , Lucas Judy , Mandiyan Sreekala , Follettie Max , Diesl Veronica , Sum Fuk-Wah , Powell Dennis , Haney Steve , Abraham Robert , Arndt Kim
Published: November 2008

Tumor necrosis factor α (TNFα) has been used to treat patients with certain tumor types. However, its antitumor activity has been undermined by the activation of IκBα kinase (IKK), which in turn activates nuclear factor-κB (NF-κB) to help cancer cells survive. Therefore, inhibition of TNFα-induced IKK activity with specific IKK inhibitor represents an attractive strategy to treat cancer patients. This study reveals IKI-1 as a potent small molecule inhibitor of IKKα and IKKβ, which effectively blocked TNFα-mediated IKK activation and subsequent NF-κB activity. Using gene profiling analysis, we show that IKI-1 blocked most of the TNFα-mediated mRNA expression, including many genes that play important roles in cell survival. We further show that in vitro and in vivo combination of TNFα with IKI-1 had superior potency than either agent alone. This increased potency was due primarily to the increased apoptosis in the presence of both TNFα and IKI-1. Additionally, IKKβ small interfering RNA transfected cells were more sensitive to the treatment of TNFα. The study suggests that the limited efficacy of TNFα in cancer treatment was due in part to the activation of NF-κB, allowing tumor cells to escape apoptosis. Therefore, the combination of IKI-1 with TNFα may improve the efficacy of TNFα for certain tumor types. [Cancer Res 2008;68(22):9519–24]