bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear spectral dynamics of a transitioning flow
Authors: Ritz Ch. P. , Powers E. J. , Miksad R. W. , Solis R. S.
Published: July 2002

The nonlinear spectral dynamics of a transitioning flow in the wake of a flat plate is experimentally studied at different downstream positions with a two-point method. The measurement setup consists of two sensors, which are separated in the downstream direction. The quadratically nonlinear transfer function between the two points is then estimated from the digitized fluctuation data. Such transfer functions permit one to quantify the quadratically nonlinear spectral dynamics occurring between the two sensor points. The method used to estimate the transfer functions and local bicoherency for non-Gaussian input and output signals, by means of digital spectral analysis techniques, is briefly discussed. The measured quadratic transfer function of the experimental data changes gradually with downstream distance, but its main features are unchanged. The observed appearance of progressively higher harmonics of the fundamental mode and the filling in of the spectral valleys over short downstream distances are, thus, mainly caused by spectral redistribution of energy that is available in the interacting modes and not caused by abrupt changes in the coupling properties. This result is supported by the local bicoherency measurements.
Effects of channel cross-sectional geometry on long wave generation and propagation
Authors: Teng Michelle H. , Wu Theodore Y.
Published: July 2002

Joint theoretical and experimental studies are carried out to investigate the effects of channel cross-sectional geometry on long wave generation and propagation in uniform shallow water channels. The existing channel Boussinesq and channel KdV equations are extended in the present study to include the effects of channel sidewall slope at the waterline in the first-order section-mean equations. Our theoretical results show that both the channel cross-sectional geometry below the unperturbed water surface (characterized by a shape factor κ) and the channel sidewall slope at the waterline (represented by a slope factor γ) affect the wavelength (λ) and time period (Ts) of waves generated under resonant external forcing. A quantitative relationship between λ, Ts, κ, and γ is given by our theory which predicts that, under the condition of equal mean water depth and equal mean wave amplitude, λ and Ts increase with increasing κ and γ. To verify the theoretical results, experiments are conducted in two channels of different geometries, namely a rectangular channel with κ≡1, γ=0 and a trapezoidal channel with κ=1.27, γ=0.16, to measure the wavelength of free traveling solitary waves and the time period of wave generation by a towed vertical hydrofoil moving with critical speed. The experimental results are found to be in broad agreement with the theoretical predictions.
Rheology of dense bubble suspensions
Authors: Kang Sang-Yoon , Sangani Ashok S. , Tsao Heng-Kwong , Koch Donald L.
Published: July 2002

The rheological behavior of rapidly sheared bubble suspensions is examined through numerical simulations and kinetic theory. The limiting case of spherical bubbles at large Reynolds number Re and small Weber number We is examined in detail. Here, Re=ργa2/μ and We=ργ2a3/s, a being the bubble radius, γ the imposed shear, s the interfacial tension, and μ and ρ, respectively, the viscosity and density of the liquid. The bubbles are assumed to undergo elastic bounces when they come into contact; coalescence can be prevented in practice by addition of salt or surface-active impurities. The numerical simulations account for the interactions among bubbles which are assumed to be dominated by the potential flow of the liquid caused by the motion of the bubbles and the shear-induced collision of the bubbles. A kinetic theory based on Grad’s moment method is used to predict the distribution function for the bubble velocities and the stress in the suspension. The hydrodynamic interactions are incorporated in this theory only through their influence on the virtual mass and viscous dissipation in the suspension. It is shown that this theory provides reasonable predictions for the bubble-phase pressure and viscosity determined from simulations including the detailed potential flow interactions. A striking result of this study is that the variance of the bubble velocity can become large compared with (γa)2 in the limit of large Reynolds number. This implies that the disperse-phase pressure and viscosity associated with the fluctuating motion of the bubbles is quite significant. To determine whether this prediction is reasonable even in the presence of nonlinear drag forces induced by bubble deformation, we perform simulations in which the bubbles are subject to an empirical drag law and show that the bubble velocity variance can be as large as 15γ2a2.
Hydrodynamics of a compound drop with application to leukocyte modeling
Authors: Kan Heng-Chuan , Udaykumar H. S. , Shyy Wei , Tran-Son-Tay Roger
Published: July 2002

We study the dynamics of a compound liquid drop which is comprised of an outer membrane surface, a shell layer, and a core. The deformation due to an imposed extensional flow and the subsequent recovery are investigated computationally employing a combined Eulerian–Lagrangian technique. The numerical method allows for large viscosity and capillarity differences between layers. The present study reports several findings which provide direct insight into developing a dynamic model for leukocytes. A compound drop behaves like a homogeneous, simple liquid drop if the core is sufficiently deformed and the time scale of the core, related to the combination of its viscosity and capillarity, is comparable to that of the shell layer. Disparate time scales between the core and shell layer result in a rapid initial recoil of the drop during which the shell fluid is the primary participant in the hydrodynamics, followed by a slower relaxation period during which the core and shell layer interact with each other. Consequently, the apparent viscosity of the drop depends not only on the rheological properties of the drop, but also on the flow dynamics surrounding it. The findings obtained with the three-layer compound drop model can explain several main characteristics of leukocytes reported in the literature. Furthermore, our study suggests that unless the presence and possible deformation of the nucleus are explicitly accounted for, neither Newtonian nor non-Newtonian models for leukocytes can adequately predict the hydrodynamics of leukocytes.
Two-phase modeling of deflagration-to-detonation transition in granular materials: A critical examination of modeling issues
Authors: Bdzil J. B. , Menikoff R. , Son S. F. , Kapila A. K. , Stewart D. S.
Published: July 2002

The two-phase mixture model developed by Baer and Nunziato (BN) to study the deflagration-to-detonation transition (DDT) in granular explosives is critically reviewed. The continuum-mixture theory foundation of the model is examined, with particular attention paid to the manner in which its constitutive functions are formulated. Connections between the mechanical and energetic phenomena occurring at the scales of the grains, and their manifestations on the continuum averaged scale, are explored. The nature and extent of approximations inherent in formulating the constitutive terms, and their domain of applicability, are clarified. Deficiencies and inconsistencies in the derivation are cited, and improvements suggested. It is emphasized that the entropy inequality constrains but does not uniquely determine the phase interaction terms. The resulting flexibility is exploited to suggest improved forms for the phase interactions. These improved forms better treat the energy associated with the dynamic compaction of the bed and the single-phase limits of the model. Companion papers of this study [Kapila et al., Phys. Fluids 9, 3885 (1997); Kapila et al., in preparation; Son et al., in preparation] examine simpler, reduced models, in which the fine scales of velocity and pressure disequilibrium between the phases allow the corresponding relaxation zones to be treated as discontinuities that need not be resolved in a numerical computation.
Does the tracer gradient vector align with the strain eigenvectors in 2D turbulence?
Authors: Lapeyre G. , Klein P. , Hua B. L.
Published: July 2002

This paper investigates the dynamics of tracer gradient for a two-dimensional flow. More precisely, the alignment of the tracer gradient vector with the eigenvectors of the strain-rate tensor is studied theoretically and numerically. We show that the basic mechanism of the gradient dynamics is the competition between the effects due to strain and an effective rotation due to both the vorticity and to the rotation of the principal axes of the strain-rate tensor. A nondimensional criterion is derived to partition the flow into different regimes: In the strain dominated regions, the tracer gradient vector aligns with a direction different from the strain axes and the gradient magnitude grows exponentially in time. In the strain-effective rotation compensated regions, the tracer gradient vector aligns with the bisector of the strain axes and its growth is only algebraic in time. In the effective rotation dominated regions, the tracer gradient vector is rotating but is often close to the bisector of the strain axes. A numerical simulation of 2D (two-dimensional) turbulence clearly confirms the theoretical preferential directions in strain and effective rotation dominated regions. Effective rotation can be dominated by the rotation rate of the strain axes, and moreover, proves to be larger than strain rate on the periphery of vortices. Taking into account this term allows us to improve significantly the Okubo–Weiss criterion. Our criterion gives the correct behavior of the growth of the tracer gradient norm for the case of axisymmetric vortices for which the Okubo–Weiss criterion fails.
Theory of toroidal Alfvén modes excited by energetic particles in tokamaks
Authors: Zonca Fulvio , Chen Liu
Published: July 2002

A general analytical theory for the two-dimensional eigenmode structures and stability of high toroidal-mode-number (high-n) shear Alfvén modes in axisymmetric tokamaks is presented. This theory, thus, further generalizes the previous work on the high-n toroidal Alfvén eigenmode (TAE) [Phys. Fluids B 5, 3668 (1993)] by including, nonperturbatively, plasma kinetic effects and resonant excitations by energetic particles. Specifically, in addition to recovering the known theoretical predictions on TAE, we have derived new results on global radial structures, as well as stability properties of kinetic toroidal Alfvén eigenmodes (KTAE) and energetic-particle modes (EPM).
Spectroscopic characterization of the DIII-D divertor
Authors: Isler R. C. , Wood R. W. , Klepper C. C. , Brooks N. H. , Fenstermacher M. E. , Leonard A. W.
Published: July 2002

Radiative losses along a fixed view into the divertor chamber of the DIII-D tokamak [Plasma Physics Controlled Nuclear Fusion Research 1986 (International Atomic Energy Agency, Vienna, 1987), Vol I, p. 159] have been characterized for attached and partially detached discharges by analyzing line-integrated vacuum ultraviolet (VUV) signals. Essentially all the emission can be ascribed to carbon and deuterium. Because the majority of the most intense lines, which lie at wavelengths above 1100 Å, are not accessible to the present instrumentation, extensive use has been made of collisional-radiative (CR) calculations for level populations of the important ions in order to relate the total radiated power to shorter wavelength transitions. In beam-heated plasmas, the fraction of radiation detected from carbon along the VUV spectrometer view is usually between 50% and 80% of the total. Carbon densities are estimated from a simplified approach to modelling the emission using a one-dimensional transport code. For partially detached plasmas the concentrations range from 2%–6% of the electron density; but in attached plasmas it appears that carbon may supply most of the electrons in the divertor region just below the X point. Ion temperatures are measured from Doppler broadening of spectral lines by fitting measured profiles to theoretical lineshapes, which account precisely for atomic sublevel splitting caused by the Zeeman/Paschen-Back effect in the tokamak magnetic field.
Neoclassical tearing modes in Tokamak Fusion Test Reactor experiments. I. Measurements of magnetic islands and Δ′
Authors: Chang Z. , Fredrickson E. D. , Batha S. H. , Bell M. G. , Budny R. V. , Levinton F. M. , McGuire K. M. , Taylor G. , Zarnstorff M. C. ,   TFTR Group
Published: July 2002

Tearing-type modes are observed in most high confinement operation regimes in the Tokamak Fusion Test Reactor (TFTR) [Nucl. Fusion 35, 1429 (1995)]. Three different methods are used to measure the magnetic island widths: external magnetic coils, internal temperature fluctuation from electron cyclotron emission (ECE) diagnostics and an experiment where the plasma major radius is rapidly shifted (“Jog” experiments). A good agreement between the three methods is observed. Numerical and analytic calculations of Δ′ (the tearing instability index) are compared with an experimental measurement of Δ′ using the tearing mode eigenfunction mapped from the jog data. The obtained negative Δ′ indicates that the observed tearing modes cannot be explained by the classical current-gradient-driven tearing theory.
The continuum of unstable magnetohydrodynamic modes in a simple magnetized atmosphere
Authors: Widdowson S. , Hurricane O. A. , Cowley S. C.
Published: July 2002

The spectrum of unstable perturbations of a simple magnetized atmosphere is studied. Magnetic field lines are straight, horizontal, and line tied to conducting walls at both ends. The temperature has horizontal variation across the field lines as well as vertical variation. The unstable spectrum close to marginal stability is found to be continuous from zero to a maximum growth rate. The structure of the unstable continuum modes is calculated in the dissipationless limit. The presence of singularities in the eigenfunction does not affect the growth rate significantly, nor does it lead to plasma heating.
Magnetohydrodynamic stability of tokamak edge plasmas
Authors: Connor J. W. , Hastie R. J. , Wilson H. R. , Miller R. L.
Published: July 2002

A new formalism for analyzing the magnetohydrodynamic stability of a limiter tokamak edge plasma is developed. Two radially localized, high toroidal mode number n instabilities are studied in detail: a peeling mode and an edge ballooning mode. The peeling mode, driven by edge current density and stabilized by edge pressure gradient, has features which are consistent with several properties of tokamak behavior in the high confinement “H”-mode of operation, and edge localized modes (or ELMs) in particular. The edge ballooning mode, driven by the pressure gradient, is identified; this penetrates ∼n1/3 rational surfaces into the plasma (rather than ∼n1/2, expected from conventional ballooning mode theory). Furthermore, there exists a coupling between these two modes and this coupling provides a picture of the ELM cycle.
Electron magnetohydrodynamic turbulence
Authors: Biskamp D. , Schwarz E. , Zeiler A. , Celani A. , Drake J. F.
Published: July 2002

Electron magnetohydrodynamic (EMHD) turbulence is studied in two- and three-dimensional (2D and 3D) systems. Results in 2D are particularly noteworthy. Energy dissipation rates are found to be independent of the diffusion coefficients. The energy spectrum follows a k−5/3 law for kde>1 and k−7/3 for kde<1, which is consistent with a local spectral energy transfer independent of the linear wave properties, contrary to magnetohydrodynamic (MHD) turbulence, where the Alfvén effect dominates the transfer dynamics. In 3D spectral properties are similar to those in 2D.
Measurement of core velocity fluctuations and the dynamo in a reversed-field pinch
Authors: Den Hartog D. J. , Chapman J. T. , Craig D. , Fiksel G. , Fontana P. W. , Prager S. C. , Sarff J. S.
Published: July 2002

Plasma flow velocity fluctuations have been directly measured in the high-temperature magnetically confined plasma in the Madison Symmetric Torus (MST) Reversed-Field Pinch (RFP) [R. N. Dexter et al., Fusion Technol. 19, 131 (1991)]. These measurements show that the flow velocity fluctuations are correlated with magnetic field fluctuations such that the electromotive force 〈ṽ×B̃〉 approximately balances parallel Ohm’s law, E∥+〈ṽ×B̃〉∥=ηJ∥. This initial measurement is subject to limitations of spatial localization and other uncertainties, but is evidence for sustainment of the RFP magnetic field configuration by the magnetohydrodynamic (MHD) dynamo, 〈ṽ×B̃〉. Both the flow velocity and magnetic field fluctuations are the result of global resistive MHD modes of helicity m=1, n=5–10 in the core of MST. Chord-averaged flow velocity fluctuations are measured in the core of MST by recording the Doppler shift of impurity line emission with a specialized high resolution and throughput grating spectrometer. Magnetic field fluctuations are recorded with a large array of small edge pickup coils, which allows spectral decomposition into discrete modes and subsequent correlation with the velocity fluctuation data.
High-temperature dynamic hohlraums on the pulsed power driver Z
Authors: Nash T. J. , Derzon M. S. , Chandler G. A. , Leeper R. , Fehl D. , Lash J. , Ruiz C. , Cooper G. , Seaman J. F. , McGurn J. , Lazier S. , Torres J. , Jobe D. , Gilliland T. , Hurst M. , Mock R. , Ryan P. , Nielsen D. , Armijo J. , McKenney J. , Hawn R. , Hebron D. , MacFarlane J. J. , Petersen D. , Bowers R. , Matuska W. , Ryutov D. D.
Published: July 2002

In the concept of the dynamic hohlraum an imploding Z pinch is optically thick to its own radiation. Radiation may be trapped inside the pinch to give a radiation temperature inside the pinch greater than that outside the pinch. The radiation is typically produced by colliding an outer Z-pinch liner onto an inner liner. The collision generates a strongly radiating shock, and the radiation is trapped by the outer liner. As the implosion continues after the collision, the radiation temperature may continue to increase due to ongoing PdV (pressure times change in volume) work done by the implosion. In principal, the radiation temperature may increase to the point at which the outer liner burns through, becomes optically thin, and no longer traps the radiation. One application of the dynamic hohlraum is to drive an ICF (inertial confinement fusion) pellet with the trapped radiation field. Members of the dynamic hohlraum team at Sandia National Labs have used the pulsed power driver Z (20 MA, 100 ns) to create a dynamic hohlraum with temperature linearly ramping from 100 to 180 eV over 5 ns. On this shot zp214 a nested tungsten wire array of 4 and 2 cm diam with masses of 2 and 1 mg imploded onto a 2.5 mg plastic annulus at 5 mm diam. The current return can on this shot was slotted. It is likely the radiation temperature may be increased to over 200 eV by stabilizing the pinch with a solid current return can. A current return can with nine slots imprints nine filaments onto the imploding pinch. This degrades the optical trapping and the quality of the liner collision. A 1.6 mm diam capsule situated inside this dynamic hohlraum of zp214 would see 15 kJ of radiation impinging on its surface before the pinch itself collapses to a 1.6 mm diam. Dynamic hohlraum shots including pellets were scheduled to take place on Z in September of 1998.
Analytical solutions to the Grad–Shafranov equation for tokamak equilibrium with dissimilar source functions
Authors: Mc Carthy P. J.
Published: July 2002

Exact solutions to the Grad–Shafranov equation for ideal magnetohydrodynamic (MHD) tokamak equilibria with dissimilar functional dependences of the pressure and poloidal current source profiles are presented. The current density profile has three free parameters, which is sufficiently flexible to describe equilibria consistent with external magnetic measurements. Experimental x-point and limiter plasma configurations can be represented by a superposition of solutions with the same eigenvalue. Both normal and reversed shear current profiles are allowed. An efficient algorithm for least squares fitting of numerically obtained experimental equilibria to the exact solution functions is described and applied to the ASDEX Upgrade (axially symmetric divertor experiment) tokamak [Plasma Physics and Controlled Nuclear Fusion Research 1992 (International Atomic Energy Agency, Vienna, 1993), Vol. I, p. 127].
Exploring the limits of the National Ignition Facility’s capsule coupling
Authors: Suter L. , Rothenberg J. , Munro D. , Van Wonterghem B. , Haan S.
Published: July 2002

The original ignition “point designs” (circa 1992) for the National Ignition Facility (NIF) [J. A. Paisner, E. M. Campbell, and W. J. Hogan, Fusion Technol. 26, 755 (1994)] were made energetically conservative to provide margin for uncertainties in laser absorption, x-ray conversion efficiency and hohlraum-capsule coupling. Since that time, extensive experiments on Nova [J. T. Hunt and D. R. Speck, Opt. Eng. 28, 461 (1989)] and Omega [J. M. Soures et al., Phys. Plasmas 3, 2108 (1996)] and their related analysis indicate that NIF coupling efficiency may be almost “as good as we could hope for.” Given close agreement between experiment and theory/modeling, one can credibly explore target enhancements which couple more of NIFs energy to an ignition capsule. These include using optimized mixtures of materials to reduce x-ray wall losses, slightly reduced laser entrance holes, and laser operation strategies which increase the amount of energy one can extract from NIF. It is found that 3–4× increases in absorbed capsule energy appear possible, providing a potentially more robust target and ∼10× increase in capsule yield.
Mode conversion electron heating in Alcator C-Mod: Theory and experiment
Authors: Bonoli P. T. , Brambilla M. , Nelson-Melby E. , Phillips C. K. , Porkolab M. , Schilling G. , Taylor G. , Wukitch S. J. , Boivin R. L. , Boswell C. J. , Fiore C. L. , Gangadhara S. , Goetz J. , Granetz R. , Greenwald M. , Hubbard A. E. , Hutchinson I. H. , In Y. , Irby J. , LaBombard B. , Lipschultz B. , Marmar E. , Mazurenko A. , Nachtrieb R. , Pappas D. , Pitcher C. S. , Reardon J. , Rice J. , Rowan W. L. , Snipes J. A. , Takase Y. , Terry J. , Wolfe S. M.
Published: July 2002

Localized electron heating [full width at half maximum of Δ(r/a)≈0.2] by mode converted ion Bernstein waves (IBW) has been observed in the Alcator C-Mod tokamak [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)]. These experiments were performed in D(3He) plasmas at high magnetic field (B0=7.9 T), high-plasma density (ne0⩾1.5×1020 m−3), and for 0.05⩽nHe-3/ne⩽0.30. Electron heating profiles of the mode converted IBW were measured using a break in slope analysis of the electron temperature versus time in the presence of rf (radio frequency) modulation. The peak position of electron heating was found to be well-correlated with He3 concentration, in agreement with the predictions of cold plasma theory. Recently, a toroidal full-wave ion cyclotron range of frequencies (ICRF) code TORIC [M. Brambilla, Nucl. Fusion 38, 1805 (1998)] was modified to include the effects of IBW electron Landau damping at (k⊥ρi)2≫1, This model was used in combination with a 1D (one-dimensional) integral wave equation code METS [D. N. Smithe et al., Radio Frequency Power in Plasmas, AIP Conf. Proc. 403 (1997), p. 367] to analyze these experiments. Model predictions were found to be in qualitative and in some instances quantitative agreement with experimental measurements. A model for mode conversion current drive (MCCD) has also been developed which combines a toroidal full wave code with an adjoint evaluation of the ICRF current drive efficiency. Predictions for off-axis MCCD in C-Mod have been made using this model and will be described.
Excitation of zonal flow by drift waves in toroidal plasmas
Authors: Chen Liu , Lin Zhihong , White Roscoe
Published: July 2002

An analytical dispersion relation is derived which shows that, in toroidal plasmas, zonal flows can be spontaneously excited via modulations in the radial envelope of a single-n coherent drift wave, with n the toroidal mode number. Predicted instability features are verified by three-dimensional global gyrokinetic simulations of the ion-temperature-gradient mode. Nonlinear equations for mode amplitudes demonstrate saturation of the linearly unstable pump wave and nonlinear oscillations of the drift-wave intensity and zonal flows, with a parameter-dependent period doubling route to chaos.
Magnetic properties of the Nd2(Fe1−xCox)14B system
Authors: Matsuura Y. , Hirosawa S. , Yamamoto H. , Fujimura S. , Sagawa M.
Published: July 2002

We have investigated the magnetic properties of the Nd2(Fe1−xCox)14B system to improve the thermal properties of the Nd-Fe-B magnets. Nd2(Fe1−xCox)14B exists in the tetragonal form in the entire range of 0≤x≤1. In this system, the replacement of Fe by Co significantly increases the Curie temperature. The room-temperature magnetization of Nd2(Fe1−xCox)14B has its maximum value at x=0.1. However, because of the decrease in the anisotropy energy and the saturation magnetization by further substitution of Co for Fe, a reasonable substitution range of Co is suggested to be x<0.2 in the sintered Nd-Fe-B magnet. In this range of Co, we have succeeded in improving the reversible temperature coefficient of the remanence for the Nd-Fe-B magnets.
Effect of electronic strain on photoacoustic generation in silicon
Authors: Stearns R. G. , Kino G. S.
Published: July 2002

The photogeneration of excess free carriers gives rise to a mechanical strain in semiconductors. An experiment has been performed to investigate the contribution of this electronic strain to photoacoustic generation, and it is found that electronic strain is an important mechanism in the photogeneration of acoustic waves in silicon. A theory is developed to predict the contribution of the electronic strain to the photoacoustic generation and is found to agree well with experiment.
Measurement of in-plane magnetization by force microscopy
Authors: Abraham David W. , Williams C. C. , Wickramasinghe H. K.
Published: July 2002

We present data which show that the magnetic force microscope is capable of detecting the component of the magnetic field parallel to the surface of a sample under study. Images of bits in a Co-alloy thin-film disk and of laser-written bits in a TbFe film were taken with a magnetized tip tilted at 45° with respect to the surface normal. In both cases the asymmetric part of the image of a domain is interpreted in terms of gradients in the in-plane component of the magnetic field. The bits written in the Co-alloy disk were decorated with small magnetized particles, allowing identification of the domain boundaries and the asymmetric component of the force microscope image due to in-plane magnetization.
West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy
Authors: Pletnev Alexander G. , Putnak Robert , Speicher Jim , Wagar Eric J. , Vaughn David W.
Published: July 2002

A candidate live attenuated vaccine strain was constructed for West Nile virus (WN), a neurotropic flavivirus that has recently emerged in the U.S. Considerable attenuation for mice was achieved by chimerization with dengue virus type 4 (DEN4). The genes for the structural premembrane and envelope proteins of DEN4 present in an infectious cDNA clone were replaced by the corresponding genes of WN strain NY99. Two of 18 cDNA clones of a WN/DEN4 chimera yielded full-length RNA transcripts that were infectious when transfected into susceptible cells. The two infectious clones shared a motif in the transmembrane signal domain located immediately downstream of the NS2B-NS3 protease cleavage site that separates the DEN4 capsid protein and the WN premembrane protein of the chimera. This motif, Asp and Thr at a position 3 and 6 amino acids downstream of the cleavage site, respectively, was not present in the 16 noninfectious cDNA clones. The WN/DEN4 chimera was highly attenuated in mice compared with its WN parent; the chimera was at least 28,500 times less neurovirulent in suckling mice inoculated intracerebrally and at least 10,000 times less virulent in adult mice inoculated intraperitoneally. Nonetheless, the WN/DEN4 chimera and a deletion mutant derived from it were immunogenic and provided complete protection against lethal WN challenge. These observations provide the basis for pursuing the development of a live attenuated WN vaccine.
The
Brucella suis virB
operon is induced intracellularly in macrophages
Authors: Boschiroli Maria Laura , Ouahrani-Bettache Safia , Foulongne Vincent , Michaux-Charachon Sylvie , Bourg Gisele , Allardet-Servent Annick , Cazevieille Chantal , Liautard Jean Pierre , Ramuz Michel , O'Callaghan David
Published: July 2002

A type IV secretion system similar to the VirB system of the phytopathogen
Agrobacterium tumefaciens
is essential for the intracellular survival and multiplication of the mammalian pathogen
Brucella
. Reverse transcriptase–PCR showed that the 12 genes encoding the
Brucella suis
VirB system form an operon. Semiquantitative measurements of
virB
mRNA levels by slot blotting showed that transcription of the
virB
operon, but not the flanking genes, is regulated by environmental factors
in vitro
. Flow cytometry used to measure green fluorescent protein expression from the
virB
promoter confirmed the data from slot blots. Fluorescence-activated cell sorter analysis and fluorescence microscopy showed that the
virB
promoter is induced in macrophages within 3 h after infection. Induction only occurred once the bacteria were inside the cells, and phagosome acidification was shown to be the major signal inducing intracellular expression. Because phagosome acidification is essential for the intracellular multiplication of
Brucella
, we suggest that it is the signal that triggers the secretion of unknown effector molecules. These effector molecules play a role in the remodeling of the phagosome to create the unique intracellular compartment in which
Brucella
replicates.
The mammalian oocyte orchestrates the rate of ovarian follicular development
Authors: Eppig John J. , Wigglesworth Karen , Pendola Frank L.
Published: July 2002

The development of both the mammalian oocyte and the somatic cell compartments of the ovarian follicle is highly coordinated; this coordination ensures that the ovulated oocyte is ready to undergo fertilization and subsequent embryogenesis. Disruption of this synchrony results in oocyte developmental failure. Communication between the oocyte and companion somatic cells is essential for successful development of both follicular compartments. However, it was not previously known whether one cell type, either the somatic or the germ cell compartment, determines the overall rate of follicular development. To test the hypothesis that the oocyte orchestrates the rate of follicle development, mid-sized oocytes isolated from secondary follicles were transferred back to primordial follicles, the earliest stage of follicular development. This transfer doubled the rate of follicular development and the differentiation of follicular somatic cells. Oocyte development in these accelerated follicles appeared normal; recovered oocytes were competent to undergo fertilization and embryonic development. These results demonstrate that oocytes orchestrate and coordinate the development of mammalian ovarian follicles and that the rate of follicular development is based on a developmental program intrinsic to the oocyte.
RETRACTED: Deficient Smad7 expression: A putative molecular defect in scleroderma
Authors: Dong Chunming , Zhu Shoukang , Wang Tao , Yoon Woohyun , Li Zhiru , Alvarez Rene J. , ten Dijke Peter , White Barbara , Wigley Fredrick M. , Goldschmidt-Clermont Pascal J.
Published: July 2002

Scleroderma is a chronic systemic disease that leads to fibrosis of affected organs. Transforming growth factor (TGF) β has been implicated in the pathogenesis of scleroderma. Smad proteins are signaling transducers downstream from TGF-β receptors. Three families of Smads have been identified: (
i
) receptor-regulated Smad2 and -3 (R-Smads); (
ii
) common partner Smad4 (Co-Smad); and (
iii
) inhibitory Smad6 and -7 (I-Smads, part of a negative feedback loop). We have investigated the signaling components for the TGF-β pathway and TGF-β activity in scleroderma lesions
in vivo
and in scleroderma fibroblasts
in vitro
. Basal level and TGF-β-inducible expression of Smad7 are selectively decreased, whereas Smad3 expression is increased both in scleroderma skin and in explanted scleroderma fibroblasts in culture. TGF-β signaling events, including phosphorylation of Smad2 and -3, and transcription of the
PAI-1
gene are increased in scleroderma fibroblasts, relative to normal fibroblasts.
In vitro
adenoviral gene transfer with Smad7 restores normal TGF-β signaling in scleroderma fibroblasts. These results suggest that alterations in the Smad pathway, including marked Smad7 deficiency and Smad3 up-regulation, may be responsible for TGF-β hyperresponsiveness observed in scleroderma.
Simulating materials failure by using up to one billion atoms and the world's fastest computer: Brittle fracture
Authors: Abraham Farid F. , Walkup Robert , Gao Huajian , Duchaineau Mark , Diaz De La Rubia Tomas , Seager Mark
Published: July 2002

We describe the first of two large-scale atomic simulation projects on materials failure performed on the 12-teraflop ASCI (Accelerated Strategic Computing Initiative) White computer at Lawrence Livermore National Laboratory. This is a multimillion-atom simulation study of crack propagation in rapid brittle fracture where the cracks travel faster than the speed of sound. Our finding centers on a bilayer solid that behaves under large strain like an interface crack between a soft (linear) material and a stiff (nonlinear) material. We verify that the crack behavior is dominated by the local (nonlinear) wave speeds, which can be in excess of the conventional sound speeds of a solid.
Supramolecular chemistry and self-assembly
Authors: Menger Fredric M.
Published: July 2002

Supramolecular systems—their successes, problems, and potential—are discussed with allusion to specific examples.
Structures of two molluscan hemocyanin genes: Significance for gene evolution
Authors: Lieb Bernhard , Altenhein Benjamin , Markl Jürgen , Vincent Alexandra , van Olden Erin , van Holde Kensal E. , Miller Karen I.
Published: July 2002

We present here the description of genes coding for molluscan
hemocyanins. Two distantly related mollusks,
Haliotis
tuberculata
and
Octopus dofleini
, were studied.
The typical architecture of a molluscan hemocyanin subunit, which is a
string of seven or eight globular functional units (FUs, designated a
to h, about 50 kDa each), is reflected by the gene organization: a
series of eight structurally related coding regions in
Haliotis
, corresponding to FU-a to FU-h, with seven
highly variable linker introns of 174 to 3,198 bp length (all in phase
1). In
Octopus
seven coding regions (FU-a to FU-g) are
found, separated by phase 1 introns varying in length from 100 bp to
910 bp. Both genes exhibit typical signal (export) sequences, and in
both cases these are interrupted by an additional intron. Each gene
also contains an intron between signal peptide and FU-a and in the 3′
untranslated region. Of special relevance for evolutionary
considerations are introns interrupting those regions that encode a
discrete functional unit. We found that five of the eight FUs in
Haliotis
each are encoded by a single exon, whereas
FU-f, FU-g, and FU-a are encoded by two, three and four exons,
respectively. Similarly, in
Octopus
four of the FUs each
correspond to an uninterrupted exon, whereas FU-b, FU-e, and FU-f each
contain a single intron. Although the positioning of the introns
between FUs is highly conserved in the two mollusks, the introns within
FUs show no relationship either in location nor phase. It is proposed
that the introns between FUs were generated as the eight-unit
polypeptide evolved from a monomeric precursor, and that the internal
introns have been added later. A hypothesis for evolution of the
ring-like quaternary structure of molluscan hemocyanins is presented.
Mechanisms of migraine aura revealed by functional MRI in human visual cortex
Authors: Hadjikhani Nouchine , Sanchez del Rio Margarita , Wu Ona , Schwartz Denis , Bakker Dick , Fischl Bruce , Kwong Kenneth K. , Cutrer F. Michael , Rosen Bruce R. , Tootell Roger B. H. , Sorensen A. Gregory , Moskowitz Michael A.
Published: July 2002

Cortical spreading depression (CSD) has been suggested to underlie
migraine visual aura. However, it has been challenging to test this
hypothesis in human cerebral cortex. Using high-field functional MRI
with near-continuous recording during visual aura in three subjects, we
observed blood oxygenation level-dependent (BOLD) signal changes that
demonstrated at least eight characteristics of CSD, time-locked to
percept/onset of the aura. Initially, a focal increase in BOLD signal
(possibly reflecting vasodilation), developed within extrastriate
cortex (area V3A). This BOLD change progressed contiguously and slowly
(3.5 ± 1.1 mm/min) over occipital cortex, congruent with the
retinotopy of the visual percept. Following the same retinotopic
progression, the BOLD signal then diminished (possibly reflecting
vasoconstriction after the initial vasodilation), as did the BOLD
response to visual activation. During periods with no visual
stimulation, but while the subject was experiencing scintillations,
BOLD signal followed the retinotopic progression of the visual percept.
These data strongly suggest that an electrophysiological event such as
CSD generates the aura in human visual cortex.
Density-dependent decline of host abundance resulting from a new infectious disease
Authors: Hochachka Wesley M. , Dhondt André A.
Published: July 2002

Although many new diseases have emerged within the past 2 decades [Cohen, M. L. (1998)Brit. Med. Bull.54, 523–532], attributing low numbers of animal hosts to the existence of even a new pathogen is problematic. This is because very rarely does one have data on host abundance before and after the epizootic as well as detailed descriptions of pathogen prevalence [Dobson, A. P. & Hudson, P. J. (1985) inEcology of Infectious Diseases in Natural Populations, eds. Grenfell, B. T. & Dobson, A. P. (Cambridge Univ. Press, Cambridge, U.K.), pp. 52–89]. Month by month we tracked the spread of the epizootic of an apparently novel strain of a widespread poultry pathogen,Mycoplasma gallisepticum, through a previously unknown host, the house finch, whose abundance has been monitored over past decades. Here we are able to demonstrate a causal relationship between high disease prevalence and declining house finch abundance throughout the eastern half of North America because the epizootic reached different parts of the house finch range at different times. Three years after the epizootic arrived, house finch abundance stabilized at similar levels, although house finch abundance had been high and stable in some areas but low and rapidly increasing in others. This result, not previously documented in wild populations, is as expected from theory if transmission of the disease was density dependent.
Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia
Authors: Hakak Yaron , Walker John R. , Li Cheng , Wong Wing Hung , Davis Kenneth L. , Buxbaum Joseph D. , Haroutunian Vahram , Fienberg Allen A.
Published: July 2002

Neuropathological and brain imaging studies suggest that
schizophrenia may result from neurodevelopmental defects.
Cytoarchitectural studies indicate cellular abnormalities suggestive of
a disruption in neuronal connectivity in schizophrenia, particularly in
the dorsolateral prefrontal cortex. Yet, the molecular mechanisms
underlying these findings remain unclear. To identify molecular
substrates associated with schizophrenia, DNA microarray analysis was
used to assay gene expression levels in postmortem dorsolateral
prefrontal cortex of schizophrenic and control patients. Genes
determined to have altered expression levels in schizophrenics relative
to controls are involved in a number of biological processes, including
synaptic plasticity, neuronal development, neurotransmission, and
signal transduction. Most notable was the differential expression of
myelination-related genes suggesting a disruption in oligodendrocyte
function in schizophrenia.
Lessons from the past: Biotic recoveries from mass extinctions
Authors: Erwin Douglas H.
Published: July 2002

Although mass extinctions probably account for the disappearance of less than 5% of all extinct species, the evolutionary opportunities they have created have had a disproportionate effect on the history of life. Theoretical considerations and simulations have suggested that the empty niches created by a mass extinction should refill rapidly after extinction ameliorates. Under logistic models, this biotic rebound should be exponential, slowing as the environmental carrying capacity is approached. Empirical studies reveal a more complex dynamic, including positive feedback and an exponential growth phase during recoveries. Far from a model of refilling ecospace, mass extinctions appear to cause a collapse of ecospace, which must be rebuilt during recovery. Other generalities include the absence of a clear correlation between the magnitude of extinction and the pace of recovery or the resulting ecological and evolutionary disruption the presence of a survival interval, with few originations, immediately after an extinction and preceding the recovery phase, and the presence of many lineages that persist through an extinction event only to disappear during the subsequent recovery. Several recoveries include numerous missing lineages, groups that are found before the extinction, then latter in the recovery, but are missing during the initial survival–recovery phase. The limited biogeographic studies of recoveries suggest considerable variability between regions.
Local translation of classes of mRNAs that are targeted to neuronal dendrites
Authors: Eberwine James , Miyashiro Kevin , Kacharmina Janet Estee , Job Christy
Published: July 2002

The functioning of the neuronal dendrite results from a variety of biological processes including mRNA transport to and protein translation in the dendrite. The complexity of the mRNA population in dendrites suggests that specific biological processes are modulated through the regulation of dendritic biology. There are various classes of mRNAs in dendrites whose translation modulates the ability of the dendrite to receive and integrate presynaptic information. Among these mRNAs are those encoding selective transcription factors that function in the neuronal soma and ionotropic glutamate receptors that function on the neuronal membrane. Conclusive evidence that these mRNAs can be translated is reviewed, and identification of the endogenous sites of translation in living dendrites is presented. These data, as well as those described in the other articles resulting from this colloquium, highlight the complexity of dendritic molecular biology and the exquisitely selective and sensitive modulatory role played by the dendrite in facilitating intracellular and intercellular communication.
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Authors: Kim Jason K. , Fillmore Jonathan J. , Chen Yan , Yu Chunli , Moore Irene K. , Pypaert Marc , Lutz E. Peer , Kako Yuko , Velez-Carrasco Wanda , Goldberg Ira J. , Breslow Jan L. , Shulman Gerald I.
Published: July 2002

Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic–euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. Muscle–lipoprotein lipase mice had a 3-fold increase in muscle triglyceride content and were insulin resistant because of decreases in insulin-stimulated glucose uptake in skeletal muscle and insulin activation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity. In contrast, liver–lipoprotein lipase mice had a 2-fold increase in liver triglyceride content and were insulin resistant because of impaired ability of insulin to suppress endogenous glucose production associated with defects in insulin activation of insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity. These defects in insulin action and signaling were associated with increases in intracellular fatty acid-derived metabolites (i.e., diacylglycerol, fatty acyl CoA, ceramides). Our findings suggest a direct and causative relationship between the accumulation of intracellular fatty acid-derived metabolites and insulin resistance mediated via alterations in the insulin signaling pathway, independent of circulating adipocyte-derived hormones.
Altered synaptic plasticity in a mouse model of fragile X mental retardation
Authors: Huber Kimberly M. , Gallagher Sean M. , Warren Stephen T. , Bear Mark F.
Published: July 2002

Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the
Fmr1
gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.
Mutational switch of an IL-6 response to an interferon-γ-like response
Authors: Costa-Pereira Ana P. , Tininini Silvia , Strobl Birgit , Alonzi Tonino , Schlaak Joerg F. , Is'harc Hayaatun , Gesualdo Ida , Newman Sally J. , Kerr Ian M. , Poli Valeria
Published: July 2002

Signaling through Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is central to the responses to the majority of cytokines and some growth factors, including the interferons (IFNs) and the IL-6 family of cytokines. The biological responses to stimulation through the widely distributed IL-6 and IFN-γ receptors are, however, completely different. Remarkably, it is shown here that, in mouse embryo fibroblasts lacking STAT3, IL-6 mediates an IFN-γ-like response including prolonged activation of STAT1, the induction of multiple IFN-γ-inducible genes, the expression of class II MHC antigens, and an antiviral state. Normal cells exposed to IL-6 thus require a STAT3-dependent function(s) to down-regulate STAT1 activity and prevent an IFN-γ-like response. The data encourage the view that the very disparate IFN-γ and IL-6 JAK/receptor complexes mediate a common set of generic or “core” signals which are subject to STAT3-dependent modulation to provide IL-6 specificity. The switching of one cytokine response to one closely mimicking another as a result of the loss of a single signaling component has profound implications, for example, for the interpretation of the phenotypes of knockout mice and for the clinical use of inhibitors of signaling.