bluuebunny/crossref_metadata_2025 huggingface dataset:
Ideal stability of cylindrical plasma in the presence of mass flow
Authors: Bondeson A. , Iacono R.
Published: July 2002

The ideal stability of cylindrical plasma with mass flows is investigated using the guiding center plasma (GCP) model of Grad [Proceedings of the Symposium on Electromagnetic and Fluid Dynamics of Gaseous Plasmas (Polytechnic Inst. of Brooklyn, New York, 1961), p. 37]. For rotating plasmas, the kinetic treatment of the parallel motion in GCP gives significantly different results from the fluid models, where the pressures are obtained from equations of state. In particular, GCP removes the resonance with slow magnetoacoustic waves and the loss of stability that occurs in magnetohydrodynamics (MHD) for near-sonic flows. Because of the strong kinetic damping of the sound waves in an isothermal plasma, the slow waves have little influence on plasma stability in GCP at low beta. In the large aspect ratio, low-beta tokamak ordering, Alfvénic flows are needed to change the ideal GCP stability significantly. At lowest order in the inverse aspect ratio, flow can be favorable or unfavorable for stability of local modes depending on the profiles, but external kinks are always destabilized by flow if the velocity vanishes at the edge. For high-beta, reversed field pinch equilibria, numerical computations show that flow can be stabilizing for local modes, but external modes are destabilized by flow. In three dimensions, the MHD equilibrium problem becomes hyperbolic for arbitrarily small flows across the magnetic field, whereas the GCP equilibrium equation remains elliptic for sub-Alfvénic flows.
Statistical properties of ideal three-dimensional magnetohydrodynamics
Authors: Stribling T. , Matthaeus W. H.
Published: July 2002

Classical Gibbs ensemble methods are used to study the spectral structure of three-dimensional ideal magnetohydrodynamics (MHD) in periodic geometry. The intent of this work is to provide further detail and extensions to the work of Frisch et al. [J. Fluid Mech. 68, 769 (1975)], who used equilibrium ensemble methods to predict inverse spectral transfer of magnetic helicity. Here, the equilibrium ensemble incorporates constraints of total energy, magnetic helicity, and cross helicity. Several new results are proven for ensemble averages, including the constraint that magnetic energy equal or exceed kinetic energy, and that cross helicity represents a constant fraction of magnetic energy across the spectral domain, for arbitrary size systems. Two zero temperature limits are considered in detail, emphasizing the role of complete and partial condensation of spectral quantities to the longest wavelength states. The ensemble predictions are compared to direct numerical solution using a low-order truncation Galerkin spectral code. Implications for spectral transfer of nonequilibrium, dissipative turbulent MHD systems are discussed.
Alpha-particle losses from toroidicity-induced Alfvén eigenmodes. Part II: Monte Carlo simulations and anomalous alpha-loss processes
Authors: Sigmar D. J. , Hsu C. T. , White R. , Cheng C. Z.
Published: July 2002

Fusion-born α particles moving parallel to the magnetic field can resonate with toroidal Alfvén eigenmodes (TAE) leading to anomalous α-orbit diffusion across the α-loss boundaries in a tokamak. This is analyzed using the Hamiltonian guiding center code orbit in conjunction with the kinetic magnetohydrodynamics (MHD) eigenmode solving code nova-k. Resonant single α orbits are studied below and above the threshold for orbit stochasticity and Monte Carlo randomized ensembles of alphas subjected to a finite amplitude time-dependent TAE are followed with respect to their radial losses using realistic MHD equilibria and numerically computed toroidal Alfvén eigenfunctions for one toroidal eigenmode n=1 and the full Fourier spectrum of poloidal harmonics m involved in the ‘‘gap mode.’’ The α-loss mechanisms are resonant drift motion across the loss boundaries of alphas born near these boundaries and stochastic diffusion to the boundaries in constants of the motion (phase) space. After a first transient of resonant drift losses scaling as B̃r/B0, the number of alphas lost via diffusion scales as (B̃r/B0)2. For TAE amplitudes B̃r/ B0≥10−3, α orbit stochasticity sets in and, depending on the radial width of the fast α density nα(r), a substantial fraction of alphas can be lost in one slowing down time. For B̃r/ B0<10−4, the losses become insignificant.
Nonlinear studies of m=1 modes in high-temperature plasmas
Authors: Aydemir A. Y.
Published: July 2002

Nonlinear evolution of the m=1 mode is examined in high-temperature plasmas where the mode is in the semicollisional or collisionless regime. Unlike the finite −Δ′(m≥2) tearing modes, the nonlinear evolution of which is collisional, both the semicollisional and collisionless m=1 modes exhibit nonlinearly enhanced growth rates that far exceed their linear values, thus making their nonlinear evolution collisionless; this accelerated growth of a collisionless m=1 mode may explain the fast sawtooth crashes observed in large tokamaks.
A method for calculating neoclassical transport coefficients with momentum conserving collision operator
Authors: Taguchi M.
Published: July 2002

A method for calculating the neoclassical transport coefficients in a nonaxisymmetric multispecies plasma is developed by employing a momentum conserving collision operator. In this method, the parallel current, and the radial particle and heat fluxes are expressed in terms of the transport coefficients which can be obtained by solving the drift kinetic equations with the pitch-angle scattering collision operator. These expressions can be easily incorporated into the existing numerical codes including the pitch-angle scattering collisions only.
Passive transport in steady Rayleigh–Bénard convection
Authors: Solomon T. H. , Gollub J. P.
Published: July 2002

Enhancement of the diffusive transport of impurities by two-dimensional, time-independent Rayleigh–Bénard convection is studied experimentally. Two impurities are used: a molecular dye (methylene blue) and a particulate impurity (latex spheres). The convective flow is characterized by laser Doppler velocimetry, and the transport is monitored by optical absorption techniques. It is found that the transport can be modeled as a diffusive process on long space and time scales, with an effective diffusion coefficient D* whose absolute magnitude and variation with the velocity amplitude W of the flow are in good agreement with recent theoretical predictions. The enhancement factor D*/D scales with the Peclet number approximately as Pe1/2≡(Wd/πD)1/2, where D is the diffusion coefficient and d the layer depth. Several subtle problems that complicate the study of transport phenomena in cellular hydrodynamic flows are discussed.
Hydrodynamic transport properties of hard-sphere dispersions. II. Porous media
Authors: Phillips R. J. , Brady J. F. , Bossis G.
Published: July 2002

The hydrodynamic transport properties of hard-sphere dispersions are calculated for volume fractions (φ) spanning the dilute limit up to the fluid–solid transition at φ=0.49. Particle distributions are generated by a Monte Carlo technique and the hydrodynamic interactions are calculated by Stokesian dynamics simulation. The effects of changing the number of particles in the simulation cell are investigated, and the scaling laws for the finite-size effects are determined. The effects of using various levels of approximation in computing both the far- and near-field hydrodynamic interactions are also examined. The transport properties associated with porous media—permeabilities and hindered diffusion coefficients—are determined here. The corresponding properties of freely mobile suspensions are determined in a companion paper [Phys. Fluids 31, xxxx (1988)].
Liquid film flow in a fracture between two porous blocks
Authors: Dindoruk Birol , Firoozabadi Abbas
Published: July 2002

Liquid film flow in a fracture between two porous bodies is mainly driven by pressure. The pressure drop across such a small distance could be significant. The flow of a liquid film is governed by the pressure drop across the fracture space, and therefore, understanding of liquid film flow in a single liquid bridge along a solid wall between two porous bodies is needed. The shape of the liquid bridge between the porous blocks is an unknown. The first step is to determine the shape of the free surface. Due to the nature of the problem, a boundary integral technique is found to provide the solution to the whole problem. Solutions are reported for a range of capillary numbers observed in cracked porous media. Pressure drop is correlated using a dimensionless capillary number group. Using analogy from the Darcy flow in porous media, a correlation for the equivalent Darcy permeability is developed.
Finite thermal diffusivity at onset of convection in autocatalytic systems: Discontinuous fluid density
Authors: Vasquez Desiderio A. , Edwards Boyd F. , Wilder Joseph W.
Published: July 2002

A linear convective stability analysis for propagating autocatalytic reaction fronts includes density differences due to both thermal and chemical gradients. Critical parameters for the onset of convection are calculated for an unbounded geometry, a vertical slab, and a vertical cylinder. Thermal effects are important at unstable wavelengths well above the critical wavelength for the onset of convection.
Wave damping by a thin layer of viscous fluid
Authors: Jenkins Alastair D. , Jacobs Stanley J.
Published: July 2002

The rate of damping of surface gravity–capillary waves is investigated, in a system which consists of a thin layer of a Newtonian viscous fluid of thickness d floating on a Newtonian fluid of infinite depth. The surface and interfacial tensions, elasticities and viscosities are taken into account. In particular, an approximate dispersion relation is derived for the case where kd and (ω/ν+)1/2d are both small, where k is the wavenumber, ω is the angular frequency and ν+ is the kinematic viscosity of the upper fluid. If d→0 while ν+d remains finite, published dispersion relations for viscoelastic surface films of extremely small (e.g., monomolecular) thickness are reproduced, if we add the surface and interfacial tensions, elasticities and viscosities together, and then add an additional 4ρ+ν+d to the surface viscosity, where ρ+ is the density of the upper fluid. A simple approximation is derived for the damping rate and associated frequency shift when their magnitudes are both small. An example is given of what may happen with a slick of heavy fuel oil on water: a slick 10 μm thick produces a damping rate only slightly different from that of a film of essentially zero thickness, but the effect of the finite thickness becomes very noticeable if it is increased to 0.1–1 mm.
Structure of Alfvén waves at the skin-depth scale
Authors: Morales G. J. , Loritsch R. S. , Maggs J. E.
Published: July 2002

This analytical study demonstrates that shear Alfvén waves having transverse scale on the order of the electron skin depth exhibit a collisionless divergence determined by propagation cones that emanate from the edges of the exciting structures. Axial current channels are found to spread radially due to the skin effect up to the cone trajectories and at distances of a few wavelengths from the exciter develop radial diffraction patterns. For values of the collision frequency slightly larger than the wave frequency resistive diffusion allows the axial currents to expand beyond the cone trajectories.
Stable equilibria for bootstrap-current-driven low aspect ratio tokamaks
Authors: Miller R. L. , Lin-Liu Y. R. , Turnbull A. D. , Chan V. S. , Pearlstein L. D. , Sauter O. , Villard L.
Published: July 2002

Low aspect ratio tokamaks (LATs) can potentially provide a high ratio of plasma pressure to magnetic pressure β and high plasma current I at a modest size. This opens up the possibility of a high-power density compact fusion power plant. For the concept to be economically feasible, bootstrap current must be a major component of the plasma current, which requires operating at high βp. A high value of the Troyon factor βN and strong shaping is required to allow simultaneous operation at a high-β and high bootstrap fraction. Ideal magnetohydrodynamic stability of a range of equilibria at aspect ratio 1.4 is systematically explored by varying the pressure profile and shape. The pressure and current profiles are constrained in such a way as to assure complete bootstrap current alignment. Both βN and β are defined in terms of the vacuum toroidal field. Equilibria with βN⩾8 and β∼35%–55% exist that are stable to n=∞ ballooning modes. The highest β case is shown to be stable to n=0,1,2,3 kink modes with a conducting wall.
Global approach to the spectral problem of microinstabilities in tokamak plasmas using a gyrokinetic model
Authors: Brunner S. , Fivaz M. , Tran T. M. , Vaclavik J.
Published: July 2002

A solution to the full two-dimensional eigenvalue problem of electrostatic microinstabilities in a tokamak plasma is presented in the framework of gyrokinetic theory. The approach is the generalization of methods previously developed for a cylindrical system [S. Brunner and J. Vaclavik, Phys. Plasmas 5, 365 (1998)]. By solving the spectral problem in a special Fourier space adapted to the curved geometry, orbit width as well as Larmor radius can be kept to all orders. For a first numerical implementation, a large aspect ratio plasma with circular concentric magnetic surfaces is considered. A root finding algorithm for identifying the eigenfrequencies, based on a higher order Nyquist method, enables straightforward implementation on a parallel computer. Illustrative results for ion temperature gradient-related instabilities are presented. These include scaling studies of the radial width, and toroidicity and magnetic shear scans, as well as the effects of nonadiabatic trapped electron dynamics.
Neutral particle and radiation effects on Pfirsch–Schlüter fluxes near the edge
Authors: Catto Peter J. , Helander P. , Connor J. W. , Hazeltine R. D.
Published: July 2002

The edge plasma of a tokamak is affected by atomic physics processes and can have density and temperature variations along the magnetic field that strongly modify edge transport. A closed system of equations in the Pfirsch–Schlüter regime is presented that can be solved for the radial and poloidal variation of the plasma density, electron and ion temperatures, and the electrostatic potential in the presence of neutrals and a poloidally asymmetric energy radiation sink due to inelastic electron collisions. Neutrals have a large diffusivity so their viscosity and heat flux can become important even when their density is not high, in which case the neutral viscosity alters the electrostatic potential at the edge by introducing strong radial variation. The strong parallel gradient in the electron temperature that can arise in the presence of a localized radiation sink drives a convective flow of particles and heat across the field. This plasma transport mechanism can balance the neutral influx and is particularly strong if multifaceted asymmetric radiation from the edge (MARFE) occurs, since the electron temperature then varies substantially over the flux surface.
Diamagnetic stabilization of ideal ballooning modes in the edge pedestal
Authors: Rogers B. N. , Drake J. F.
Published: July 2002

The stability of the tokamak edge pedestal to ballooning modes is addressed using three-dimensional simulations of the Braginskii equations and simple analytic models. The effects of ion diamagnetic drift and the finite radial localization of the pedestal pressure gradient are found to be strongly stabilizing when δ<δR, where δ is the pedestal half-width and δR∼ρi2/3R1/3 in the center of the pedestal. In this limit, conventional ballooning modes within the pedestal region become stable, and a stability condition is obtained in the two fluid system α/αc<(4/3)δR/δ (stable) which is much less stringent than that predicted by local magnetohydrodynamic (MHD) theory (α/αc<1). Given α∼q2Rβ/δ, this condition implies a stability limit on the pedestal β: β<βc, where βc=(4αc/3q2)δR/R. This limit is due the onset of an ideal pressure driven “surface” instability that depends only on the pressure drop across the pedestal. Near marginal conditions, this mode has a poloidal wavenumber kθ∼1/δR, a radial envelope ∼δR(>δ), and real frequency ω∼cs/δRR.
A model for the interaction of superthermal electrons with the magnetohydrodynamic modes during electron cyclotron resonant heating
Authors: Lazaros Avrilios
Published: July 2002

The interaction of electron cyclotron resonant heating (ECRH) with the m/n=2/1 magnetohydrodynamic (MHD) mode, which was observed in toroidal plasmas, is attributed to the superthermal electrons that are produced on the EC resonance by the ECRH. Superthermal electrons, as they drift across the q=2 surface, exchange power with the m/n=2/1 MHD mode which is either suppressed or enhanced. When the EC resonance is outside the rational surface, the mode is always suppressed. When the EC resonance is inside the rational surface, modes with a large amplitude are enhanced while modes with a small amplitude are suppressed.
Growth and nonlinear evolution of the modified Simon-Hoh instability in an electron beam-produced plasma
Authors: Sakawa Y. , Joshi C.
Published: July 2002

The growth and nonlinear evolution of the modified Simon–Hoh instability (MSHI) is observed in a weak electron beam-produced collisionless cylindrical plasma, in which electrons are strongly magnetized and the ions are essentially unmagnetized. The evolution of this instability occurs through a sequence of sideband instabilities, thought to be induced by trapped ions, and a period doubling sequence. Transient study of the MSHI reveals that the growth rate of the MSHI is extremely rapid; of the order the instability frequency.
Modification of high mode pedestal instabilities in the DIII-D tokamak
Authors: Ferron J. R. , Chu M. S. , Jackson G. L. , Lao L. L. , Miller R. L. , Osborne T. H. , Snyder P. B. , Strait E. J. , Taylor T. S. , Turnbull A. D. , Garofalo A. M. , Makowski M. A. , Rice B. W. , Chance M. S. , Baylor L. R. , Murakami M. , Wade M. R.
Published: July 2002

The amplitude and frequency of modes driven in the edge region of tokamak high mode (H-mode) discharges [type I edge-localized modes (ELMs)] are shown to depend on the discharge shape. The measured pressure gradient threshold for instability and its scaling with discharge shape are compared with predictions from ideal magnetohydrodynamic theory for low toroidal mode number (n) instabilities driven by pressure gradient and current density and good agreement is found. Reductions in mode amplitude are observed in discharge shapes with either high squareness or low triangularity where the stability threshold in the edge pressure gradient is predicted to be reduced and the most unstable mode is expected to have higher values of n. The importance of access to the ballooning mode second stability regime is demonstrated through the changes in the ELM character that occur when second regime access is not available. An edge stability model is presented that predicts that there is a threshold value of n for second regime access and that the most unstable mode has n near this threshold.
Shock waves in charge-varying dusty plasmas and the effect of electromagnetic radiation
Authors: Popel S. I. , Gisko A. A. , Golub’ A. P. , Losseva T. V. , Bingham R. , Shukla P. K.
Published: July 2002

Nonlinear electrostatic wave structures in dusty plasmas in the presence of electromagnetic radiation are investigated. The dust charge variation is assumed to be caused by microscopic electron and ion currents at the grains as well as photoelectric current of electrons. Calculations of electromagnetic radiation effects are performed for the case of solar radiation spectrum in the vicinity of the earth. The exact solutions of the nonlinear equations, describing variable-charge dust grains, Boltzmann electrons, and inertial ions, are obtained in the form of steady-state shocks. The conditions for their existence are found. The dissipation in such shock waves originates from the process of dust charging. The possibility of observation of shock waves related to the dust charging process in the presence of electromagnetic radiation in active rocket experiments which involve the release of some gaseous substance in near-earth space is discussed.
1.54-μm electroluminescence of erbium-doped silicon grown by molecular beam epitaxy
Authors: Ennen H. , Pomrenke G. , Axmann A. , Eisele K. , Haydl W. , Schneider J.
Published: July 2002

The feasibility of producing erbium-doped silicon light-emitting diodes by molecular beam epitaxy is demonstrated. The p-n junctions are formed by growing an erbium-doped p-type epitaxial silicon layer on an n-type silicon substrate. When the diodes are biased in the forward direction at 77 K they show an intense sharply structured electroluminescence spectrum at 1.54 μm. This luminescence is assigned to the internal 4f–4f transition 4I13/2→4I15/2 of Er3+ (4f11).
Elastic wave attenuation in rocks containing fluids
Authors: Berryman James G.
Published: July 2002

The low-frequency limit of Biot’s theory of fluid-saturated porous media predicts that the coefficients for viscous attenuation of shear waves and of the fast compressional wave are proportional to the fluid permeability. Although the observed attenuation is generally in qualitative agreement with the theory, the magnitude of the observed attenuation coefficient in rocks is often more than an order of magnitude higher than expected. This apparent dilemma can be resolved without invoking other attenuation mechanisms if the intrinsic permeability of the rock is inhomogeneous and varies widely in magnitude. A simple calculation of the overall behavior of a layered porous material using local-flow Biot theory shows that the effective permeability for attenuation is the mean of the constituent permeabilities while the effective permeability for fluid flow is the harmonic mean. When the range of variation in the local permeability is one or more orders of magnitude, this difference in averaging method can easily explain some of the observed discrepancies.
Picosecond transient reflectivity of unpinned gallium arsenide (100) surfaces
Authors: Beck S. M. , Wessel J. E.
Published: July 2002

Surface recombination was measured for photowashed and unwashed GaAs using picosecond transient photoreflectance methods. The results for the washed surfaces clearly demonstrate slow surface recombination that is accurately described by an ambipolar diffusion model. The fast decay observed for unwashed samples implies rapid surface recombination involving a more complex mechanism.
Time-resolved photoacoustic studies of vascular tissue ablation at three laser wavelengths
Authors: Cross F. W. , Al-Dhahir R. K. , Dyer P. E. , MacRobert A. J.
Published: July 2002

Nanosecond-time-resolved photoacoustic transducers have been used to study the subthreshold and ablation response of vascular tissue irradiated with short laser pulses at 248, 308, and 532 nm. Attenuation coefficients, ablation thresholds, and ablation time scales can be obtained in this way providing new information on the laser-tissue interaction problem.
Epitaxial growth of Al(111)/Si(111) films using partially ionized beam deposition
Authors: Choi C.-H. , Harper R. A. , Yapsir A. S. , Lu T.-M.
Published: July 2002

We observed the growth of epitaxial Al(111) films on Si(111) at room temperature by the partially ionized beam deposition technique. The films were deposited in a conventional vacuum condition without in situ cleaning. The beam contained 0.3% of Al self-ions and a bias potential of 1 kV was applied to the substrate during deposition. X-ray diffraction (pole figure) revealed that one of the two possible twin structures, with the Al〈1̄10〉∥Si〈1̄10〉 orientation, was preferentially grown on the Si substrate.
Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis
Authors: Hamelink Carol , Tjurmina Olga , Damadzic Ruslan , Young W. Scott , Weihe Eberhard , Lee Hyeon-Woo , Eiden Lee E.
Published: July 2002

The adrenal gland is important for homeostatic responses to
metabolic stress: hypoglycemia stimulates the splanchnic nerve,
epinephrine is released from adrenomedullary chromaffin cells, and
compensatory glucogenesis ensues. Acetylcholine is the primary
neurotransmitter mediating catecholamine secretion from the adrenal
medulla. Accumulating evidence suggests that a secretin-related
neuropeptide also may function as a transmitter at the adrenomedullary
synapse. Costaining with highly specific antibodies against the
secretin-related neuropeptide pituitary adenylate cyclase-activating
peptide (PACAP) and the vesicular acetylcholine transporter (VAChT)
revealed that PACAP is found in nerve terminals at all mouse
adrenomedullary cholinergic synapses. Mice with a targeted deletion of
the PACAP gene had otherwise normal cholinergic innervation and
morphology of the adrenal medulla, normal adrenal catecholamine and
blood glucose levels, and an intact initial catecholamine secretory
response to insulin-induced hypoglycemia. However, insulin-induced
hypoglycemia was more profound and longer-lasting in PACAP knock-outs,
and was associated with a dose-related lethality absent in wild-type
mice. Failure of PACAP-deficient mice to adequately counterregulate
plasma glucose levels could be accounted for by impaired long-term
secretion of epinephrine, secondary to a lack of induction of tyrosine
hydroxylase, normally occurring after insulin hypoglycemia in wild-type
mice, and a consequent depletion of adrenomedullary epinephrine stores.
Thus, PACAP is needed to couple epinephrine biosynthesis to secretion
during metabolic stress. PACAP appears to function as an “emergency
response” cotransmitter in the sympathoadrenal axis, where the
primary secretory response is controlled by a classical
neurotransmitter but sustained under paraphysiological conditions by a
neuropeptide.
Conservation of
Pax 6
function and upstream activation by
Notch
signaling in eye development of frogs and flies
Authors: Onuma Yasuko , Takahashi Shuji , Asashima Makoto , Kurata Shoichiro , Gehring Walter J.
Published: July 2002

Loss of
Pax 6
function leads to an eyeless phenotype in both mammals and insects, and ectopic expression of both the
Drosophila
and the mouse gene leads to the induction of ectopic eyes in
Drosophila
, which suggested to us that
Pax 6
might be a universal master control gene for eye morphogenesis. Here, we report the reciprocal experiment in which the RNAs of the
Drosophila Pax 6
homologs,
eyeless
and
twin of eyeless
, are transferred into a vertebrate embryo; i.e., early
Xenopus
embryos at the 2- and 16-cell stages. In both cases, ectopic eye structures are formed. To understand the genetic program specifying eye morphogenesis, we have analyzed the regulatory mechanisms of
Pax 6
expression that initiates eye development. Previously, we have demonstrated that
Notch
signaling regulates the expression of
eyeless
and
twin of eyeless
in
Drosophila
. Here, we show that in
Xenopus
, activation of
Notch
signaling also induces eye-related gene expression, including
Pax 6
, in isolated animal caps. In
Xenopus
embryos, the activation of
Notch
signaling causes eye duplications and proximal eye defects, which are also induced by overexpression of
eyeless
and
twin of eyeless
. These findings indicate that the gene regulatory cascade is similar in vertebrates and invertebrates.
The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals
Authors: Dolce Vincenza , Fiermonte Giuseppe , Runswick Michael J. , Palmieri Ferdinando , Walker John E.
Published: July 2002

The synthesis of DNA in mitochondria requires the uptake of
deoxynucleotides into the matrix of the organelle. We have
characterized a human cDNA encoding a member of the family of
mitochondrial carriers. The protein has been overexpressed in bacteria
and reconstituted into phospholipid vesicles where it catalyzed the
transport of all four deoxy (d) NDPs, and, less efficiently, the
corresponding dNTPs, in exchange for dNDPs, ADP, or ATP. It did not
transport dNMPs, NMPs, deoxynucleosides, nucleosides, purines, or
pyrimidines. The physiological role of this deoxynucleotide carrier is
probably to supply deoxynucleotides to the mitochondrial matrix for
conversion to triphosphates and incorporation into mitochondrial DNA.
The protein is expressed in all human tissues that were examined except
for placenta, in accord with such a central role. The deoxynucleotide
carrier also transports dideoxynucleotides efficiently. It is likely to
be medically important by providing the means of uptake into
mitochondria of nucleoside analogs, leading to the mitochondrial
impairment that underlies the toxic side effects of such drugs in the
treatment of viral illnesses, including AIDS, and in cancer therapy.
Sensitivity to
Alternaria alternata
toxin in citrus because of altered mitochondrial RNA processing
Authors: Ohtani Kouhei , Yamamoto Hiroyuki , Akimitsu Kazuya
Published: July 2002

Specificity in the interaction between rough lemon (
Citrus jambhiri
Lush.) and the fungal pathogen
Alternaria alternata
rough lemon pathotype is determined by a host-selective toxin, ACR-toxin. Mitochondria from rough lemon are sensitive to ACR-toxin whereas mitochondria from resistant plants, including other citrus species, are resistant. We have identified a
C. jambhiri
mitochondrial DNA sequence, designated
ACRS
(ACR-toxin sensitivity gene), that confers toxin sensitivity to
Escherichia coli
.
ACRS
is located in the group II intron of the mitochondrial tRNA-Ala and is translated into a SDS-resistant oligomeric protein in
C. jambhiri
mitochondria but is not translated in the toxin-insensitive mitochondria.
ACRS
is present in the mitochondrial genome of both toxin-sensitive and -insensitive citrus. However, in mitochondria of toxin-insensitive plants, the transcripts from
ACRS
are shorter than those in mitochondria of sensitive plants. These results demonstrate that sensitivity to ACR-toxin and hence specificity of the interaction between
A. alternata
rough lemon pathotype and
C. jambhiri
is due to differential posttranscriptional processing of a mitochondrial gene.
Protection of cardiac mitochondria by diazoxide and protein kinase C: Implications for ischemic preconditioning
Authors: Korge Paavo , Honda Henry M. , Weiss James N.
Published: July 2002

Mitochondrial ATP-sensitive K (mitoK
ATP
) channels play a central role in protecting the heart from injury in ischemic preconditioning. In isolated mitochondria exposed to elevated extramitochondrial Ca, P
i
, and anoxia to simulate ischemic conditions, the selective mitoK
ATP
channel agonist diazoxide (25–50 μM) potently reduced mitochondrial injury by preventing both the mitochondrial permeability transition (MPT) and cytochrome
c
loss from the intermembrane space. Both effects were blocked completely by the selective mitoK
ATP
antagonist 5-hydroxydecanoate. The protective effect against Ca-induced MPT was most evident under conditions in which the ability of electron transport to support membrane potential (Δψ
m
) was decreased and inner membrane leakiness was increased moderately. Under these conditions, mitoK
ATP
channel activity strongly regulated Δψ
m
, and diazoxide prevented MPT by inhibiting the driving force for Ca uptake. Phorbol 12-myristate 13-acetate mimicked the protective effects of diazoxide, unless 5-hydroxydecanoate was present, indicating that protein kinase C activation also protects mitochondria by activating mitoK
ATP
channels. Because Δψ
m
recovery ultimately is required for heart functional recovery, these results may explain how mitoK
ATP
channel activation mimics ischemic preconditioning by protecting mitochondria as they pass through a critical vulnerability window during ischemia/reperfusion.
Vav3 is regulated during the cell cycle and effects cell division
Authors: Fujikawa Keiko , Inoue Yoshiro , Sakai Masaharu , Koyama Yoshikazu , Nishi Shinzo , Funada Ryo , Alt Frederick W. , Swat Wojciech
Published: July 2002

Vav3 is a member of the family of guanine nucleotide exchange factors implicated in the regulation of Rho GTPases. Although the exact
in vivo
function of Vav3 is unknown, evidence from several studies indicates a role distinct from Vav2 or Vav1. Here we report that the expression of Vav3 is regulated during the cell cycle. Strikingly, Vav3 was transiently up-regulated in HeLa cells during mitosis, whereas enforced expression of Vav3 perturbed cytokinesis and led to the appearance of multinucleated cells. These effects of Vav3 were RhoA-dependent, required phosphorylation of the regulatory tyrosine 173, but were not enhanced by N-terminal truncations. Thus, this report establishes that expression of Vav3 is strictly regulated in a cell cycle-dependent manner and implicates Vav3 in the control of cytokinesis.
Estimating risks in declining populations with poor data
Authors: Holmes Elizabeth E.
Published: July 2002

Census data on endangered species are often sparse, error-ridden,
and confined to only a segment of the population. Estimating trends and
extinction risks using this type of data presents numerous
difficulties. In particular, the estimate of the variation in
year-to-year transitions in population size (the “process error”
caused by stochasticity in survivorship and fecundities) is confounded
by the addition of high sampling error variation. In addition, the
year-to-year variability in the segment of the population that is
sampled may be quite different from the population variability that one
is trying to estimate. The combined effect of severe sampling error and
age- or stage-specific counts leads to severe biases in estimates of
population-level parameters. I present an estimation method that
circumvents the problem of age- or stage-specific counts and is
markedly robust to severe sampling error. This method allows the
estimation of environmental variation and population trends for
extinction-risk analyses using corrupted census counts—a common type
of data for endangered species that has hitherto been relatively
unusable for these analyses.
Cessation of rapid late endosomal tubulovesicular trafficking in Niemann–Pick type C1 disease
Authors: Zhang Mei , Dwyer Nancy K. , Love Dona C. , Cooney Adele , Comly Marcy , Neufeld Edward , Pentchev Peter G. , Blanchette-Mackie E. Joan , Hanover John A.
Published: July 2002

Niemann–Pick type C1 (NPC1) disease results from a defect in the
NPC1 protein and is characterized by a pathological accumulation of
cholesterol and glycolipids in endocytic organelles. We followed the
biosynthesis and trafficking of NPC1 with the use of a functional green
fluorescent protein-fused NPC1. Newly synthesized NPC1 is exported from
the endoplasmic reticulum and requires transit through the Golgi before
it is targeted to late endosomes. NPC1-containing late endosomes then
move by a dynamic process involving tubulation and fission, followed by
rapid retrograde and anterograde migration along microtubules. Cell
fusion studies with normal and mutant NPC1 cells show that exchange of
contents between late endosomes and lysosomes depends upon ongoing
tubulovesicular late endocytic trafficking. In turn, rapid endosomal
tubular movement requires an intact NPC1 sterol-sensing domain and is
retarded by an elevated endosomal cholesterol content. We conclude that
the neuropathology and cellular lysosomal lipid accumulation in NPC1
disease results, at least in part, from striking defects in late
endosomal tubulovesicular trafficking.
Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide
Authors: Moriyama Hiroaki , Wen Li , Abiru Norio , Liu Edwin , Yu Liping , Miao Dongmei , Gianani Roberto , Wong F. Susan , Eisenbarth George S.
Published: July 2002

Polyinosinic-polycytidylic acid (PolyIC), a “mimic” of double-stranded viral RNA, can induce diabetes when administered to rats with RT1
u
, and immunization of normal H-2
d
mice (e.g., BALB/c) with insulin B:9–23 peptide (but not H-2
b
) results in the rapid induction of insulin autoantibodies. Because a mouse model of PolyIC/antigen-induced diabetes is lacking, we sought to produce insulitis and diabetes with either PolyIC and/or B:9–23 peptide immunization. Simultaneous administration of PolyIC and B:9–23 peptide to BALB/c mice (but with neither alone) induced insulitis. CD4 T lymphocytes predominated within islets, and the mice did not progress to hyperglycemia. Islets with transgene-induced expression of the costimulatory B7–1 molecule have enhanced diabetes susceptibility. Diabetes was frequently induced in B7–1 transgenic mice with H-2
d
in contrast to H-2
b
mice after PolyIC administration. Disease induction was accelerated by adding B:9–23 immunization to PolyIC. These studies demonstrate that “normal” mice have autoreactive T lymphocytes able to rapidly target islets and insulin given appropriate MHC alleles and that a peripherally administered insulin peptide (an altered peptide ligand of which is in clinical trials) can enhance specific anti-islet autoimmunity. These first PolyIC/insulin-induced murine models should provide an important tool to study the pathogenesis of type 1 diabetes with experimental autoimmune diabetes.
Kinetics and mechanism of the DNA double helix invasion by pseudocomplementary peptide nucleic acids
Authors: Demidov Vadim V. , Protozanova Ekaterina , Izvolsky Konstantin I. , Price Christopher , Nielsen Peter E. , Frank-Kamenetskii Maxim D.
Published: July 2002

If adenines and thymines in two mutually complementary mixed-base peptide nucleic acid (PNA) oligomers are substituted with diaminopurines and thiouracils, respectively, so-called pseudocomplementary PNAs (pcPNAs) are created. Pairs of pcPNAs have recently demonstrated an ability to highly selectively target essentially any designated site on double-stranded DNA (dsDNA) by forming very stable PNA–DNA strand-displacement complexes via double duplex invasion (helix invasion). These properties of pcPNAs make them unique and very promising ligands capable of denying the access of DNA-binding proteins to dsDNA. To elucidate the sequence-unrestricted mechanism of sequence-specific dsDNA recognition by pcPNAs, we have studied the kinetics of formation of corresponding PNA–DNA complexes at various temperatures by the gel-shift assay. In parallel, the conditions for possible self-hybridization of pcPNA oligomers have been assayed by mixing curve (Job plot) and thermal melting experiments. The data indicate that, at physiological temperatures (≈37°C), the equilibrium is shifted toward the pairing of corresponding pcPNAs with each other. This finding explains a linear concentration dependence, within the submicromolar range, of the pcPNA invasion rate into dsDNA at 37°C. At elevated temperatures (>50°C), the rather unstable pcPNA duplexes dissociate, yielding the expected quadratic dependence for the rate of pcPNA invasion on the PNA concentration. The polycationic character of pcPNA pairs, carrying the duplicated number of protonated terminal PNA residues commonly used to increase the PNA solubility and binding affinity, also explains the self-inhibition of pcPNA invasion observed at higher PNA concentrations. Melting of pcPNA duplexes occurs with the integral transition enthalpies ranged from −235 to −280 kJ⋅mol
−1
, contributing to an anomalously high activation energy of ≈150 kJ⋅mol
−1
found for the helix invasion of pcPNAs carrying four different nucleobases. A simplified kinetic model for pcPNAs helix invasion is proposed that interprets all unusual features of pcPNAs binding to dsDNA. Our findings have important implications for rational use of pcPNAs.
Effective inhibition of human cytomegalovirus gene expression and replication by a ribozyme derived from the catalytic RNA subunit of RNase P from
Escherichia coli
Authors: Trang Phong , Lee Manfred , Nepomuceno Edward , Kim Joe , Zhu Hua , Liu Fenyong
Published: July 2002

A sequence-specific ribozyme (M1GS RNA) derived from the catalytic
RNA subunit of RNase P from
Escherichia coli
was used to
target the overlapping exon 3 region of the mRNAs encoding the major
transcription regulatory proteins IE1 and IE2 of human cytomegalovirus.
A reduction of more than 80% in the expression levels of IE1 and IE2
and a reduction of about 150-fold in viral growth were observed in
human cells that stably expressed the ribozyme. In contrast, a
reduction of less than 10% in the IE1/IE2 expression and viral
growth was observed in cells that either did not express the ribozyme
or produced a “disabled” ribozyme that carried mutations that
abolished its catalytic activity. Examination of the expression of
several other viral early and late genes in the cells that expressed
the M1GS ribozyme further revealed an overall reduction of at least
80% in their expression. These results are consistent with the notion
that the antiviral effects in these cells are due to the fact that the
ribozyme specifically inhibits the expression of IE1 and IE2 and,
consequently, abolishes the expression of viral early and late genes as
well as viral growth. Our study is the first, to our knowledge, to use
M1GS ribozyme for inhibiting human cytomegalovirus replication and
demonstrates the utility of this ribozyme for antiviral applications.
Three-dimensional reconstruction of the recombinant type 3 ryanodine receptor and localization of its amino terminus
Authors: Liu Zheng , Zhang Jing , Sharma Manjuli R. , Li Pin , Chen S. R. Wayne , Wagenknecht Terence
Published: July 2002

Recombinant type 3 ryanodine receptor (RyR3) has been purified in
quantities sufficient for structural characterization by cryoelectron
microscopy and three-dimensional (3D) reconstruction. Two cDNAs were
prepared and expressed in HEK293 cells, one encoding the wild-type RyR3
and the other encoding RyR3 containing glutathione
S
-transferase (GST) fused to its amino terminus
(GST-RyR3). RyR3 was purified from detergent-solubilized transfected
cells by affinity chromatography using 12.6-kDa FK506-binding protein
in the form of a GST fusion as the affinity ligand. Purification of
GST-RyR3 was achieved by affinity chromatography by using
glutathione-Sepharose. Purified recombinant RyR3 and GST-RyR3 proteins
exhibited high-affinity [
3
H]ryanodine binding that was
sensitive to activation by Ca
2+
and caffeine and to
inhibition by Mg
2+
. 3D reconstructions of both recombinant
RyR3 and GST-RyR3 appeared very similar to that of the native RyR3
purified from bovine diaphragm. Comparison of the 3D reconstructions of
RyR3 and GST-RyR3 revealed that the GST domains and, hence, the amino
termini of the RyR3 subunits are located in the “clamp”
structures that form the corners of the square-shaped cytoplasmic
region of homotetrameric RyR3. This study describes the 3D
reconstruction of a recombinant ryanodine receptor and it demonstrates
the potential of this technology for characterizing functional and
structural perturbations introduced by site-directed mutagenesis.
Domain movements in human fatty acid synthase by quantized elastic deformational model
Authors: Ming Dengming , Kong Yifei , Wakil Salih J. , Brink Jacob , Ma Jianpeng
Published: July 2002

This paper reports the results of applying a computational method called the quantized elastic deformational model, to the determination of conformational flexibility of the supermolecular complex of human fatty acid synthase. The essence of this method is the ability to model large-scale conformational changes such as domain movements by treating the protein as an elastic object without the knowledge of protein primary sequence and atomic coordinates. The calculation was based on the electron density maps of the synthase at 19 Å. The results suggest that the synthase is a very flexible molecule. Two types of flexible hinges in the structure were identified. One is an intersubunit hinge formed by the intersubunit connection and the other is an intrasubunit hinge located between domains I and II. Despite the fact that the dimeric synthase has a chemically symmetric structure, large domain movements around the hinge region occur in various directions and allow the molecule to adopt a wide range of conformations. These domain movements are likely to be important in facilitating and regulating the entire palmitate synthesis by coordinating the communication between components of the molecule, for instance, adjusting the distance between various active sites inside the catalytic reaction center. Finally, the ability to describe protein motions of a supermolecular complex, without the information of protein sequence and atomic coordinates, is a major advance in computational modeling of protein dynamics. The method provides an unprecedented ability to model protein motions at such a low resolution of structure.
Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs
Authors: Wijnholds Jan , Mol Carla A. A. M. , van Deemter Liesbeth , de Haas Marcel , Scheffer George L. , Baas Frank , Beijnen Jos H. , Scheper Rik J. , Hatse Sigrid , De Clercq Erik , Balzarini Jan , Borst Piet
Published: July 2002

Two prominent members of the ATP-binding cassette superfamily of transmembrane proteins, multidrug resistance 1 (MDR1) P-glycoprotein and multidrug resistance protein 1 (MRP1), can mediate the cellular extrusion of xenobiotics and (anticancer) drugs from normal and tumor cells. The MRP subfamily consists of at least six members, and here we report the functional characterization of human MRP5. We found resistance against the thiopurine anticancer drugs, 6-mercaptopurine (6-MP) and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in
MRP5-
transfected cells. This resistance is due to an increased extrusion of PMEA and 6-thioinosine monophosphate from the cells that overproduce MRP5. In polarized Madin–Darby canine kidney II (MDCKII) cells transfected with an
MRP5
cDNA construct, MRP5 is routed to the basolateral membrane and these cells transport
S
-(2,4-dinitrophenyl)glutathione and glutathione preferentially toward the basal compartment. Inhibitors of organic anion transport inhibit transport mediated by MRP5. We speculate that MRP5 might play a role in some cases of unexplained resistance to thiopurines in acute lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in HIV-infected patients.
All-
trans
-retinal shuts down rod cyclic nucleotide-gated ion channels: A novel role for photoreceptor retinoids in the response to bright light?
Authors: Dean Dylan M. , Nguitragool Wang , Miri Andrew , McCabe Sarah L. , Zimmerman Anita L.
Published: July 2002

In retinal rods, light-induced isomerization of 11-
cis
-retinal to all-
trans
-retinal within rhodopsin triggers an enzyme cascade that lowers the concentration of cGMP. Consequently, cyclic nucleotide-gated (CNG) ion channels close, generating the first electrical response to light. After isomerization, all-
trans
-retinal dissociates from rhodopsin. We now show that all-
trans
-retinal directly and markedly inhibits cloned rod CNG channels in excised patches. 11-
cis
-retinal and all-
trans
-retinol also inhibited the channels, but at somewhat higher concentrations. Single-channel analysis suggests that all-
trans
-retinal reduces average open probability of rod CNG channels by inactivating channels for seconds at a time. At physiological cGMP levels, all-
trans
-retinal inhibited in the nanomolar range. Our results suggest that all-
trans
-retinal may be a potent regulator of the channel in rods during the response to bright light, when there is a large surge in the concentration of all-
trans
-retinal.