bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical computation of collisionless drift Alfvén turbulence
Authors: Jenko Frank , Scott Bruce D.
Published: July 2002

An electromagnetic hybrid model of drift-kinetic electrons and cold ions in three-dimensional sheared slab geometry is constructed to treat collisionless drift Alfvén turbulence in tokamak edge plasmas. The basic nonlinear equations are solved numerically using explicit finite-difference methods on a phase-space grid rather than an ensemble of “superparticles.” Basic properties of the turbulent fluctuations such as amplitude and phase distributions, amplitude correlations, and energy spectra are investigated. The resulting turbulent particle transport by magnetic flutter is negligible compared to that by E×B convection. However, the intrinsic dynamics of the turbulence remains electromagnetic due to the influence of kinetic shear Alfvén waves and magnetic flutter. Comparisons with a companion Landau-fluid model are more successful than in similar studies of ion temperature gradient turbulence.
Statistical theory of turbulent transport (non-Markovian effects)
Authors: Zagorodny A. , Weiland J.
Published: July 2002

A transition probability approach is used to study transport caused by linear instabilities in the real (coordinate) and velocity spaces. The general non-Markovian Fokker–Planck treatment is used to derive the diffusion coefficients. The Dupree–Weinstock renormalized diffusion is reproduced in the Markovian limit. For transport in real space, the non-Markovian diffusion coefficient which is part of one of the transport models used in predicting the performance of the International Thermonuclear Experimental Reactor, [D.R. Mikkelsen, G. Bateman, D. Boucher et al., Proceedings of the Sixteenth IAEA Fusion Energy Conference, Yokohama 1998 (IAEA, Vienna, 1999) Paper IAEA-CN-69/ITER P1/08], is reproduced in a more systematic way.
Kelvin-Helmholtz driven modes of the magnetosphere
Authors: Mills Katharine J. , Wright Andrew N. , Mann Ian R.
Published: July 2002

Ultralow frequency (ULF) waves in the magnetosphere are thought to be driven by disturbances of the magnetopause caused by the flow in the magnetosheath. In this paper a model showing how the trapping and excitation of these modes depends upon the shear flow and propagation angle is presented. The ideal magnetohydrodynamics (MHD) equations are used and the perturbations are assumed to be linear. A bounded, uniform magnetospheric cavity, with a finite plasma beta, separated by a vortex sheet from a semi-infinite, field-free, flowing magnetosheath is considered. It is shown that the bounded model allows the trapping and excitation of both fast and slow cavity modes, and that unstable surface modes may also exist. Slow surface modes are unstable only for a small interval of flow speed, becoming fast surface modes for higher flows. Slow cavity modes have small growth rates and are unlikely to be significant observationally. It is shown that fast modes propagating quasiparallel to the flow may be excited for realistic flow speeds, but that for nonparallel modes, much higher flows are required. Finally, an exact method for predicting the onset of instability for fast modes is derived and is shown to occur at the coalescence of modes of opposite energy.
Stabilization of the internal kink mode in a tokamak by toroidal plasma rotation
Authors: Wahlberg C. , Bondeson A.
Published: July 2002

The stability of the internal m=n=1 kink mode is analyzed for a tokamak with a toroidally rotating plasma, by a large aspect ratio expansion of the compressible magnetohydrodynamic equations. Assuming that the central poloidal beta is of order unity, it is found that the internal kink mode is stabilized by rotational frequencies of order Ω/ωA∼ε, where ωA is the Alfvén frequency and ε is the inverse aspect ratio. The internal kink then turns into a stable oscillation with a Doppler-shifted frequency ∼ΩM(1−1/Γ)1/2, where Γ is the adiabatic index and ℳ is the sonic Mach number. The stabilization comes from the centrifugal force which gives a stable density (or entropy) distribution within each magnetic surface. The parallel motion associated with the internal kink mode then behaves as the Brunt–Väisälä oscillations of a stably stratified fluid in a gravitational field. At lower rotational frequencies, Ω/ωA∼ε2, the only effect of the rotation is a co-rotation of the usual (nonrotating) m=n=1 instability, whereas the ordering Ω/ωA∼ε3/2 represents a transition regime where the stabilizing effect of the rotation competes with the drive from the internal kink instability. Kinetic behavior along the field lines is expected to influence this stabilization mechanism, as it depends on the adiabatic index Γ.
Experimental study of fluctuations excited by a narrow temperature filament in a magnetized plasma
Authors: Burke A. T. , Maggs J. E. , Morales G. J.
Published: July 2002

A systematic study is made of the spontaneous growth of fluctuations in temperature, density, and magnetic field in a narrow (on the order of the electron skin depth) field-aligned temperature filament embedded in a large magnetized plasma. Two broad classes of fluctuation (“low” and “high” frequency modes) have been identified and studied in detail. A high-frequency drift-Alfvén mode grows at frequencies about one tenth the ion gyrofrequency in the region of the filament where the temperature gradient is large. The measured radial profiles of the density and magnetic field fluctuations associated with this mode agree well with theoretical predictions. The high-frequency mode has been observed to exhibit several interesting nonlinear features, including steepening wave form, progression in azimuthal mode number, coupling to the low frequency mode with subsequent sideband generation, and eventually a transition to broad band turbulence. The nature of the low-frequency mode which has frequencies about one fiftieth of the ion gyrofrequency is less certain, but it has been identified as a spatially localized, azimuthally symmetric mode consisting primarily of temperature fluctuations. Both the high and low-frequency modes give rise to electron heat transport at rates in excess of the classical values.
Relaxation revisited
Authors: Taylor J. B.
Published: July 2002

Relaxation is the result of turbulence in a plasma that behaves essentially as an ideal conducting fluid, but has a small resistivity and viscosity. These small effects are locally enhanced by the turbulence and lead to reconnection of magnetic field lines. This destroys an infinity of topological constraints, leaving only the total magnetic helicity as a valid invariant. The plasma therefore rapidly reaches a specific state of minimum energy. This minimum energy “relaxed state” can be calculated from first principles and has many striking features. These depend on the topology of the system. They include spontaneous field reversal, symmetry-breaking and current limitation in toroidal pinches, and flux generation and flux amplification in Spheromaks. In addition the relaxed states can be controlled and maintained by injection of helicity from an external circuit. These features, and the profiles of the relaxed states themselves, have been verified in many laboratory experiments.
Polarization of radiation in incoherent Thomson scattering by high temperature plasma
Authors: Segre S. E. , Zanza V.
Published: July 2002

The state of polarization of radiation scattered from hot plasma for any given input polarization is obtained by a relativistic derivation. Approximate analytical expressions are obtained for electron temperatures below about 10 keV. The characteristics of the scattered polarization are presented in detail for fully and linearly polarized incident radiation and their implications for the design of experiments are discussed.
Resistive X-point modes in tokamak boundary plasmas
Authors: Myra J. R. , D’Ippolito D. A. , Xu X. Q. , Cohen R. H.
Published: July 2002

It is shown that the boundary (edge and scrape-off-layer) plasma in a typical low (L) mode diverted tokamak discharge is unstable to a new class of modes called resistive X-point (RX) modes. The RX mode is a type of resistive ballooning mode that exploits a synergism between resistivity and the magnetic geometry of the X-point region. The RX modes are shown to give robust instabilities at moderate mode numbers, and therefore are expected to be the dominant contributors to turbulent diffusion in the boundary plasma of a diverted tokamak.
Nonlinear evolution of parametric instability of a large-amplitude nonmonochromatic Alfvén wave
Authors: Malara F. , Primavera L. , Veltri P.
Published: July 2002

The nonlinear evolution of the parametric instability of a finite amplitude Alfvén wave is studied in a one-dimensional geometry. The linear stage of this instability had been examined in a previous paper [Malara and Velli, Phys. Plasmas 3, 4427 (1996)], in which it has been shown that even a nonmonochromatic broad-band wave is unstable. In the present paper, the time evolution is followed up to saturation, by numerically integrating the full set of magnetohydrodynamic (MHD) equations. Several configurations of the Alfvénic pump wave, as well as different values of the plasma β are examined. The saturation level of the instability does not depend on the spectral width of the pump wave, but it depends on the value of β. For β≲0.5 the final state is characterized by a cross-helicity ∼0 and a moderate level of density fluctuations: The Alfvénic correlation of the initial wave is completely destroyed, even for a broad-band initial spectrum. For β=1 the final cross-helicity is closer to that of the initial wave, indicating a lower saturation level. The parametric process appears to be nonlocal in the wave-vector space also in the nonmonochromatic case, this feature becoming more relevant with increasing β.
High speed, ion bombarded InGaAs photoconductors
Authors: Downey P. M. , Martin R. J. , Nahory R. E. , Lorimor O. G.
Published: July 2002

Studies of the performance of n-InGaAs photoconductive detectors before and after the introduction of recombination sites via ion bombardment are described. An empirical relation between speed of response and bombardment dose by Be ions is established for this material, demonstrating that the response time can be controllably reduced by more than two orders of magnitude below the few nanosecond time which is characteristic of undamaged devices. In this same radiation dose range only moderate mobility deterioration is observed. Greater than unity photoconductive gain is demonstrated for large size (15 μm) devices with a 1/e response time of 400 ps.
Spatial dependence of particle light scattering in an rf silane discharge
Authors: Roth R. M. , Spears K. G. , Stein G. D. , Wong G.
Published: July 2002

A capacitively coupled, rf glow discharge of silane in argon was studied to determine the spatial dependence of particle light scattering. Light scattering from a pulsed laser at 500 nm shows sharp spatial peaks of scattered intensity near the electrodes. These scattering peaks are correlated with the plasma sheath edges because they exhibit spatial changes with discharge pressure characterized by a constant product of pressure and distance from the electrode. Light scattering at various silane mole fractions and gas flow rates is compatible with concepts of particle growth in sharp spatial zones near the plasma sheaths.
Picojoule, subnanosecond, all-optical switching using bound excitons in CdS
Authors: Dagenais M. , Sharfin W. F.
Published: July 2002

We use the nondiffusive nonlinearity, the large transition dipole moment, and the small spectral broadening associated with the I2 bound excitons in cadmium sulfide to achieve the lowest reported single beam switching energy (<8 pJ) and the fastest reported ON/OFF switching bistable device (<2 ns) with clearly resolved switching states. In an optimized geometry, it is shown that the fundamental limits on switching energies can be approached.
Deep electron traps in undoped, molecular beam epitaxially grown ZnSe
Authors: Yoneda Kiyoshi , Hishida Yuji , Ishii Hiroaki
Published: July 2002

Deep electron traps in normally undoped, low resistivity, molecular beam epitaxially grown ZnSe layers have been investigated by deep level transient spectroscopy. Two dominant deep electron traps with activation energies of 0.34 and 0.54 eV were observed. The former trap, whose trap concentration is independent of the carrier concentration in the grown layers, is attributed to a native defect arising from Se vacancy, while the latter, whose trap concentration increases with an increase in carrier concentration, is ascribed to the complex center associated with donor impurities incorporated during growth by evaporation of a Se source material.
Localized epitaxial growth of C54 and C49 TiSi2 on (111)Si
Authors: Fung M. S. , Cheng H. C. , Chen L. J.
Published: July 2002

Both C54 and C49 structure TiSi2 were found to grow epitaxially on (111)Si. Epitaxial regions, as large as 15 μm in size, were observed. The orientation relationships between epitaxial C54-TiSi2 and Si were determined to be [100]TiSi2//[111]Si, (004)TiSi2//(022̄)Si or [001]TiSi2//[111]Si, and (400)TiSi2//(022̄)Si, whereas those between C49-TiSi2 and Si are [31̄0]TiSi2//[112]Si and (130)TiSi2//(111̄)Si. Interfacial dislocations were identified to be of mixed type with (1)/(6)  〈112〉 Burgers vectors. The dislocation spacings were found to vary from 170 to 600 Å. Polytype structures with different spacings were observed by the lattice imaging method. The growth of the most conductive silicide epitaxially on silicon presents an exciting possibility to fabricate novel high-speed devices.
Laser-induced fluorescence studies of excimer laser ablation of Al2O3
Authors: Dreyfus R. W. , Kelly Roger , Walkup R. E.
Published: July 2002

We have used laser-induced fluorescence to measure the energy distributions of Al atoms and AlO molecules produced by excimer laser ablation of Al2O3. Excimer laser fluences close to the threshold for ablation were used to minimize the effects of gas phase collisions. The kinetic energies of both species were high, ∼4 eV for Al and ∼1 eV for AlO, but the AlO rotational and vibrational energies were quite low, corresponding to a temperature of ∼600 K. These results rule out thermal vaporization and provide indirect support for an electronic ablation mechanism.
Stark effect in AlxGa1−xAs/GaAs coupled quantum wells
Authors: Le H. Q. , Zayhowski J. J. , Goodhue W. D.
Published: July 2002

Optical spectra near the band edges of AlxGa1−xAs/GaAs coupled quantum well structures are found to exhibit rich structure. Under the Stark perturbation, these transitions have behavior remarkably different from those associated with single quantum wells. Positive energy shifts and high sensitivity to electric fields have been observed and interpreted as evidence of well coupling. Results of a simple numerical calculation support this interpretation.
Room-temperature continuous-wave operation of a GaInP/AlGaInP multiquantum well laser grown by metalorganic chemical vapor deposition
Authors: Ikeda M. , Toda A. , Nakano K. , Mori Y. , Watanabe N.
Published: July 2002

Room-temperature continuous-wave (cw) operation of a GaInP/AlGaInP multiquantum well (MQW) laser was achieved for the first time. The threshold current was 70 mA at 22 °C for a device with an 8-μm-wide and a 250-μm-long planar stripe. The emission wavelength was 668 nm. The characteristic temperature T0 was 138 K under cw operation. The wafer with the MQW structure composed of 100-Å-thick GaInP wells and 40-Å-thick AlGaInP barrier layers was grown by atmospheric pressure metalorganic chemical vapor deposition.
Arsenic-doped p-CdTe layers grown by organometallic vapor phase epitaxy
Authors: Ghandhi S. K. , Taskar N. R. , Bhat I. B.
Published: July 2002

Arsenic-doped CdTe layers have been grown by organometallic vapor phase epitaxy in an atmospheric pressure reactor using arsine as the dopant gas. Doping levels above 2×1017 cm−3 have been reproducibly obtained for the first time in an epitaxial growth system, with a doping uniformity of ±20% over 1.5×1.5 cm. This is a much higher level of doping than usually possible in bulk growth systems. The layers were characterized by photoluminescence measurements at 12 K and by Hall measurements as a function of temperature. The ionization energy of the As acceptor was found to be about 62±4 meV from transport measurements. It was also shown that the electronic activity of the As incorporated is a function of the dimethylcadmium to diethyltelluride partial pressure ratio in the gas phase.
Influence of fast neutrons on electrical properties in neutron transmutation doped GaAs: New annealing stage
Authors: Satoh M. , Kuriyama K. , Yahagi M. , Iwamura K. , Kim C. , Kawakubo T. , Yoneda K. , Kimura I.
Published: July 2002

In neutron transmutation doping (NTD) to the undoped semi-insulating GaAs, a new annealing stage related to the tunneling assisted hopping conduction was found around 400 °C for fast neutron fluences of ≥7.0×1017 n/cm2. It is suggested that this stage is based on the enhancement in the hopping conduction by the activated dopant in the NTD process. The stage was not observed for the irradiation with a small amount of fast neutrons. The activation energy for the annihilation of As antisite defects (AsGa) was found to be 0.9 eV. The annealing temperature to achieve the desired carried concentration increased with the fast neutron fluence.
Infrared Raman probing of deep-lying damaged layers in hydrogen-implanted GaAs
Authors: Anastassakis E. , Tatarkiewicz J.
Published: July 2002

We report on the use of a cw Nd:yttrium aluminum garnet infrared laser to probe by Raman scattering the damaged layers of GaAs implanted with high-energy(∼2 MeV) protons and deuterons. Such layers are too deep into the material to be probed by visible light. As the implanted area is approached laterally, we observe a gradual decrease in the scattering intensity of the longitudinal optical and transverse optical phonons and a downward shift of their frequencies. These effects are attributed to defect-induced absorption and lattice strains. The results demonstrate the advantages of the technique for studying the damage in deeply buried layers of radiation-modified materials.
Dynamic consolidation of diamond powder into polycrystalline diamond
Authors: Potter David K. , Ahrens Thomas J.
Published: July 2002

The formation of a polycrystalline solid compact, by fusing an initially porous aggregate of diamond crystals under dynamic shock pressure (7.5–18 GPa), is shown to depend critically on the size of the initial crystals. Porous aggregates of 100–150 μm diameter crystals upon shock compaction produced compacts. These exhibited pronounced fracturing of the individual crystals and showed no evidence of fusion. Aggregates consisting of ultrafine crystals (<5 μm) also exhibited minimal consolidation. However, samples composed of crystals in the range 4–8 μm produced strong fused compacts of polycrystalline diamond. A model calculation indicates that at 10 GPa less than 0.07 mass fraction of the diamond powder can be melted and this molten material is quenched in 0.8 ns for 8-μm-diam crystals.
Electroreflectance and photoluminescence studies of (AlxGa1−x)1−zInzPyAs1−y lattice matched to GaAs
Authors: Asami K. , Okuno T. , Emura S. , Gonda S. , Mukai S.
Published: July 2002

Electroreflectance (ER) measurements have been performed on an (AlxGa1−x)1−zInzPyAs1−y pentanary alloy grown on (100) GaAs in the energy range 1.3–3.8 eV at 300 K. Accurate band-gap energy has been determined from ER measurements. Photoluminescence (PL) spectra have been measured in the energy range 1.3–2.0 eV at 300 and 77 K. From the broadening parameters in ER spectra and the full width of half-maxima in PL spectra, the quality of AlGaInPAs has been discussed. The other optical features, E0+Δ0, E1, E1+Δ1, and the spin-orbit splitting parameters Δ0 and Δ1 have been determined.
Gas source silicon molecular beam epitaxy using silane
Authors: Hirayama Hiroyuki , Tatsumi Toru , Ogura Atsushi , Aizaki Naoaki
Published: July 2002

The apparatus and its preliminary results of gas source silicon molecular beam epitaxy are reported for the first time. In this study, silane (SiH4) was used as a source gas. A subchamber was designed to control the gas flow precisely. SiH4 exposure during the initial cleaning was effective in lowering the cleaning temperature and saving the cleaning time. Epitaxial silicon films grew uniformly on 4-in. wafers. There was no spitting defect on the epitaxial films. Moreover, selective epitaxial growth was realized using a patterned SiO2 mask.
Spin-dependent recombination in irradiated Si/SiO2 device structures
Authors: Vranch R. L. , Henderson B. , Pepper M.
Published: July 2002

We report studies of spin-dependent recombination at the Si/SiO2 interface in electron irradiated (100) and (111) p-channel metal-oxide-silicon field-effect transistors and metal-oxide-silicon wafers. Electron spin resonance transitions on the Pb center increase the recombination current at the Si/SiO2 interface by 2–3 parts in 104. The results are interpreted using a model involving the recombination of electrons and holes at Pb centers with which they are spatially correlated.
Twin formation and Au segregation during ion-beam-induced epitaxy of amorphous Si
Authors: Priolo F. , Batstone J. L. , Poate J. M. , Linnros J. , Jacobson D. C. , Thompson Michael O.
Published: July 2002

Ion-beam-induced epitaxial recrystallization of Au-implanted amorphous silicon at temperatures >400 °C has been studied. Crystallization was induced using a 2.5 MeV Ar beam. Segregation of Au at the moving crystal/amorphous silicon interface occurs with an interface velocity of 5 Å/s. At high Au concentrations, the interface breaks down with the formation of twins. The twinned crystal/amorphous interface then propagates under further irradiation with a reduced interface velocity of 3 Å/s. Unusual Au redistribution profiles are obtained as a result of the sudden change in interface morphology. The Au profiles are interpreted on the basis of classical segregation theory with the interfacial segregation coefficient changing from 0.0012 to 0.02 at the onset of twin formation.
Nondestructive technique for the detection of dislocations and stacking faults on silicon wafers
Authors: Witowski Bob , Smith W. Lee , Willenborg David L.
Published: July 2002

We demonstrate the imaging of dislocations and stacking faults in silicon wafers in a noncontact, nondestructive fashion using laser based modulated optical reflectance. By comparison with conventional wet decoration etching, we show that the sensitivity of the modulated optical reflectance method can resolve the difference between two types of dislocations.
Damage nucleation and annealing in MeV ion-implanted Si
Authors: Holland O. W. , El-Ghor M. K. , White C. W.
Published: July 2002

The damage produced in Si by high-energy MeV ions and its low-temperature annealing behavior are discussed. The damage morphology clearly shows that there are distinct regions in which different damage nucleation and growth mechanisms are dominant. A model is proposed to account for the observations. Both electron microscopy and Rutherford backscattering were used to characterize the damage distributions, while the annealing behavior of the damage helped in identifying some of the defects.
Isolation of peptide aptamers that inhibit intracellular processes
Authors: Blum Jonathan H. , Dove Simon L. , Hochschild Ann , Mekalanos John J.
Published: July 2002

We have developed a method for isolation of random peptides that inhibit intracellular processes in bacteria. A library of random peptides expressed as fusions to
Escherichia coli
thioredoxin (aptamers) were expressed under the tight control of the arabinose-inducible P
BAD
promoter. A selection was applied to the library to isolate aptamers that interfered with the activity of thymidylate synthase (ThyA)
in vivo
. Expression of an aptamer isolated by this method resulted in a ThyA
−
phenotype that was suppressed by simultaneous overexpression of ThyA. Two-hybrid analysis showed that this aptamer is likely to interact with ThyA
in vivo
. The library also was screened for aptamers that inhibited growth of bacteria expressing them, and five such aptamers were characterized. Four aptamers were bacteriostatic when expressed, whereas one showed a bactericidal effect. Introduction of translational stop codons into various aptamers blocked their activity, suggesting that their biological effects were likely to be due to protein aptamer rather than RNA. Combinatorial aptamers provide a new genetic and biochemical tool for identifying targets for antibacterial drug development.
Glutamic acid decarboxylase and glutamate receptor changes during tolerance and dependence to benzodiazepines
Authors: Izzo Emanuela , Auta James , Impagnatiello Francesco , Pesold Christine , Guidotti Alessandro , Costa Erminio
Published: July 2002

Protracted administration of diazepam elicits tolerance, whereas
discontinuation of treatment results in signs of dependence. Tolerance
to the anticonvulsant action of diazepam is present in an early phase
(6, 24, and 36 h) but disappears in a late phase (72–96 h) of
withdrawal. In contrast, signs of dependence such as decrease in
open-arm entries on an elevated plus-maze and increased susceptibility
to pentylenetetrazol-induced seizures were apparent 96 h (but not
12, 24, or 48 h) after diazepam withdrawal. During the first
72 h of withdrawal, tolerance is associated with changes in the
expression of GABA
A
(γ-aminobutyric acid type A) receptor
subunits (decrease in γ
2
and α
1
; increase
in α
5
) and with an increase of mRNA expression of the
most abundant form of glutamic acid decarboxylase (GAD),
GAD
67
. In contrast,
dl
-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
(AMPA) receptor GluR1 subunit mRNA and cognate protein, which are
normal during the early phase of diazepam withdrawal, increase by
approximately 30% in cortex and hippocampus in association with the
appearance of signs of dependence 96 h after diazepam withdrawal.
Immunohistochemical studies of GluR1 subunit expression with
gold-immunolabeling technique reveal that the increase of GluR1 subunit
protein is localized to layer V pyramidal neurons and their apical
dendrites in the cortex, and to pyramidal neurons and in their
dendritic fields in hippocampus. The results suggest an involvement of
GABA-mediated processes in the development and maintenance of tolerance
to diazepam, whereas excitatory amino acid-related processes
(presumably via AMPA receptors) may be involved in the expression
of signs of dependence after withdrawal.
Statistical modeling of large microarray data sets to identify stimulus-response profiles
Authors: Zhao Lue Ping , Prentice Ross , Breeden Linda
Published: July 2002

A statistical modeling approach is proposed for use in searching
large microarray data sets for genes that have a transcriptional
response to a stimulus. The approach is unrestricted with respect to
the timing, magnitude or duration of the response, or the overall
abundance of the transcript. The statistical model makes an
accommodation for systematic heterogeneity in expression levels.
Corresponding data analyses provide gene-specific information, and the
approach provides a means for evaluating the statistical significance
of such information. To illustrate this strategy we have derived a
model to depict the profile expected for a periodically transcribed
gene and used it to look for budding yeast transcripts that adhere to
this profile. Using objective criteria, this method identifies 81% of
the known periodic transcripts and 1,088 genes, which show significant
periodicity in at least one of the three data sets analyzed. However,
only one-quarter of these genes show significant oscillations in at
least two data sets and can be classified as periodic with high
confidence. The method provides estimates of the mean activation and
deactivation times, induced and basal expression levels, and
statistical measures of the precision of these estimates for each
periodic transcript.
Mechanism underlying bupivacaine inhibition of G protein-gated inwardly rectifying K
+
channels
Authors: Zhou Wei , Arrabit Christine , Choe Senyon , Slesinger Paul A.
Published: July 2002

Local anesthetics, commonly used for treating cardiac arrhythmias,
pain, and seizures, are best known for their inhibitory effects on
voltage-gated Na
+
channels. Cardiovascular and central
nervous system toxicity are unwanted side-effects from local
anesthetics that cannot be attributed to the inhibition of only
Na
+
channels. Here, we report that extracellular
application of the membrane-permeant local anesthetic bupivacaine
selectively inhibited G protein-gated inwardly rectifying
K
+
channels (GIRK:Kir3) but not other families of inwardly
rectifying K
+
channels (ROMK:Kir1 and IRK:Kir2).
Bupivacaine inhibited GIRK channels within seconds of application,
regardless of whether channels were activated through the muscarinic
receptor or directly via coexpressed G protein
G
β
γ
subunits. Bupivacaine also inhibited
alcohol-induced GIRK currents in the absence of functional pertussis
toxin-sensitive G proteins. The mutated GIRK1 and GIRK2 (GIRK1/2)
channels containing the high-affinity phosphatidylinositol
4,5-bisphosphate (PIP
2
) domain from IRK1, on the other
hand, showed dramatically less inhibition with bupivacaine.
Surprisingly, GIRK1/2 channels with high affinity for
PIP
2
were inhibited by ethanol, like IRK1 channels. We
propose that membrane-permeant local anesthetics inhibit GIRK channels
by antagonizing the interaction of PIP
2
with the channel,
which is essential for G
β
γ
and ethanol
activation of GIRK channels.
Preferential interaction of the core histone tail domains with linker DNA
Authors: Angelov Dimitar , Vitolo Joseph M. , Mutskov Vesco , Dimitrov Stefan , Hayes Jeffrey J.
Published: July 2002

Within chromatin, the core histone tail domains play critical roles
in regulating the structure and accessibility of nucleosomal DNA within
the chromatin fiber. Thus, many nuclear processes are facilitated by
concomitant posttranslational modification of these domains. However,
elucidation of the mechanisms by which the tails mediate such processes
awaits definition of tail interactions within chromatin. In this study
we have investigated the primary DNA target of the majority of the
tails in mononucleosomes. The results clearly show that the tails bind
preferentially to “linker” DNA, outside of the DNA encompassed by
the nucleosome core. These results have important implications for
models of tail function within the chromatin fiber and for
in
vitro
structural and functional studies using nucleosome core
particles.
Complementary intrastrand base pairing during initiation of Herpes simplex virus type 1 DNA replication
Authors: Aslani Alireza , Macao Bertil , Simonsson Stina , Elias Per
Published: July 2002

The herpes simplex virus type 1 origin of DNA replication, oriS, contains three copies of the recognition sequence for the viral initiator protein, origin binding protein (OBP), arranged in two palindromes. The central box I forms a short palindrome with box III and a long palindrome with box II. Single-stranded oriS adopts a conformation, oriS*, that is tightly bound by OBP. Here we demonstrate that OBP binds to a box III–box I hairpin with a 3′ single-stranded tail in oriS*. Mutations designed to destabilize the hairpin abolish the binding of OBP to oriS*. The same mutations also inhibit DNA replication. Second site complementary mutations restore binding of OBP to oriS* as well as the ability of mutated oriS to support DNA replication. OriS* is also an efficient activator of the hydrolysis of ATP by OBP. Sequence analyses show that a box III–box I palindrome is an evolutionarily conserved feature of origins of DNA replication from human, equine, bovine, and gallid alpha herpes viruses. We propose that oriS facilitates initiation of DNA synthesis in two steps and that OBP exhibits exquisite specificity for the different conformations oriS adopts at these stages. Our model suggests that distance-dependent cooperative binding of OBP to boxes I and II in duplex DNA is succeeded by specific recognition of a box III–box I hairpin in partially unwound DNA.
Abortive base-excision repair of radiation-induced clustered DNA lesions in
Escherichia coli
Authors: Blaisdell Jeffrey O. , Wallace Susan S.
Published: July 2002

It has been postulated that ionizing radiation produces a unique form of cellular DNA damage called “clustered damages” or “multiply damaged sites”. Here, we show that clustered DNA damages are indeed formed in
Escherichia coli
by ionizing radiation and are converted to lethal double-strand breaks during attempted base-excision repair. In wild-type cells possessing the oxidative DNA glycosylases that cleave DNA at repairable single damages, double-strand breaks are formed at radiation-induced clusters during postirradiation incubation and also in a dose-dependent fashion.
E. coli
mutants lacking these enzymes do not form double-strand breaks postirradiation and are substantially more radioresistant than wild-type cells. Furthermore, overproduction of one of the oxidative DNA glycosylases in mutant cells confers a radiosensitive phenotype and an increase in the number of double-strand breaks. Thus, the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk.
Rapid induction of intraneuronal neurofibrillary tangles in apolipoprotein E-deficient mice
Authors: Bi Xiaoning , Yong Alex P. , Zhou Jun , Ribak Charles E. , Lynch Gary
Published: July 2002

Cultured hippocampal slices prepared from apolipoprotein E-deficient mice were exposed to an inhibitor of cathepsins B and L and then processed for immunocytochemistry using antibodies against human paired helical filaments. Dense, AT8-immunopositive deposits were found in the subiculum, stratum oriens of hippocampal field CA1, and the hilus of the dentate gyrus. This distribution agrees with that described for tangles in Alzheimer's disease. The appearance of the labeled structures fell into categories that correspond to previously proposed stages in the progression of intraneuronal neurofibrillary tangles in human hippocampus. Electron microscopic analyses confirmed that microtubule disruption and twisted bundles of filaments were present in neurons in the affected areas. These results support the hypothesis that partial lysosomal dysfunction is a contributor to Alzheimer's disease and suggest a simple model for studying an important component of the disease.
Subcellular distribution of epothilones in human tumor cells
Authors: Lichtner R. B. , Rotgeri A. , Bunte T. , Buchmann B. , Hoffmann J. , Schwede W. , Skuballa W. , Klar U.
Published: July 2002

Epothilones are a new class of natural and potent antineoplastic
agents that stabilize microtubules. Although 12,13-epoxide derivatives
are potent antiproliferative agents, the activities of the
corresponding 12,13-olefin analogs are significantly decreased. These
data were confirmed for two new analogs, 6-propyl-EpoB (pEB) and
6-propyl-EpoD (pED), in comparison with the natural compounds
EpoB/EpoD, by using human A431, MCF7, and MDR1-overexpressing
NCI/Adr cells. By using tritiated pEB/pED, compound uptake,
release, and nuclear accumulation were investigated in A431 and
NCI/Adr cells. In these cells, epothilones can principally be
recognized and exported by Verapamil-sensitive efflux pumps, which are
not identical to MDR1. The degree of export depends on the structure,
olefin vs. epoxide-analog, and also on the intracellular drug
concentration. The accumulation of pED used at 3.5 or 70 nM,
respectively, was increased in the presence of 10 μM Verapamil in
both cell lines 2- to 8-fold. In contrast, the intracellular levels of
pEB were affected by Verapamil only at 3.5 nM pEB in NCI/Adr (2-fold)
and not in A431 cells. In addition, strong nuclear accumulation was
observed for pEB (40–50%) but not paclitaxel or pED (5–15%) in both
cell lines. Our study suggests that differences in growth inhibitory
efficacy between epoxide and olefin analogs may be based on different
mechanisms of drug accumulation and subcellular distribution.
Formation of a selenium-substituted rhodanese by reaction with selenite and glutathione: Possible role of a protein perselenide in a selenium delivery system
Authors: Ogasawara Yuki , Lacourciere Gerard , Stadtman Thressa C.
Published: July 2002

Selenophosphate is the active selenium-donor compound required by
bacteria and mammals for the specific synthesis of Secys-tRNA, the
precursor of selenocysteine in selenoenzymes. Although free selenide
can be used
in vitro
for the synthesis of
selenophosphate, the actual physiological selenium substrate has not
been identified. Rhodanese (EC
2.3.1.1
) normally occurs as a persulfide
of a critical cysteine residue and is believed to function as a
sulfur-delivery protein. Also, it has been demonstrated that a
selenium-substituted rhodanese (E-Se form) can exist
in
vitro
. In this study, we have prepared and characterized an
E-Se rhodanese. Persulfide-free bovine-liver rhodanese (E form) did not
react with SeO

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directly, but in the presence of
reduced glutathione (GSH) and SeO

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E-Se rhodanese
was generated. These results indicate that the intermediates produced
from the reaction of GSH with SeO

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are required for
the formation of a selenium-substituted rhodanese. E-Se rhodanese was
stable in the presence of excess GSH at neutral pH at 37°C. E-Se
rhodanese could effectively replace the high concentrations of selenide
normally used in the selenophosphate synthetase
in vitro
assay in which the selenium-dependent hydrolysis of ATP is measured.
These results show that a selenium-bound rhodanese could be used as the
selenium donor in the
in vitro
selenophosphate synthetase
assay.
Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease
Authors: Xia Xu Gang , Harding Thomas , Weller Michael , Bieneman Alison , Uney James B. , Schulz Jörg B.
Published: July 2002

Increasing evidence suggests that apoptosis may be the underlying cell death mechanism in the selective loss of dopaminergic neurons in Parkinson's disease. Because the inhibition of caspases provides only partial protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP
+
) model of Parkinson's disease, we investigated the role of the proapoptotic c-Jun N-terminal kinase (JNK) signaling cascade in SH-SY5Y human neuroblastoma cells
in vitro
and in mice
in vivo
. MPTP/MPP
+
led to the sequential phosphorylation and activation of JNK kinase (MKK4), JNK, and c-Jun, the activation of caspases, and apoptosis. In mice, adenoviral gene transfer of the JNK binding domain of JNK-interacting protein-1 (a scaffold protein and inhibitor of JNK) inhibited this cascade downstream of MKK4 phosphorylation, blocked JNK, c-Jun, and caspase activation, the death of dopaminergic neurons, and the loss of catecholamines in the striatum. Furthermore, the gene transfer resulted in behavioral benefit. Therefore, inhibition of the JNK pathway offers a new treatment strategy for Parkinson's disease that blocks the death signaling pathway upstream of the execution of apoptosis in dopaminergic neurons, providing a therapeutic advantage over the direct inhibition of caspases.
Pro-coagulant state resulting from high levels of soluble P-selectin in blood
Authors: André Patrick , Hartwell Daqing , Hrachovinová Ingrid , Saffaripour Simin , Wagner Denisa D.
Published: July 2002

The plasma concentration of soluble adhesion receptors is increased under pathological circumstances, but their function remains enigmatic. Soluble P-selectin (sP-sel) is shed from activated platelets and endothelial cells. Mice genetically engineered to express P-selectin without the cytoplasmic tail (ΔCT) constitutively show a 3- to 4-fold increase of sP-sel in plasma. We observed that the ΔCT mice formed fibrin very readily. In anex vivoperfusion chamber, there was more fibrin deposited at the site of platelet thrombus formation than in wild type (WT), whereas no fibrin deposits were detected using P-selectin-deficient blood during the same interval. Similarly,in vivo, the hemorrhage produced by local Shwartzman reaction was smaller in the ΔCT mice than in WT. In contrast, we previously showed hemorrhage to be more prominent in P-selectin knock-out mice. Infusion of mouse P-sel-Ig chimera produced the same protective effect in WT mice as seen in the ΔCT mice, indicating that the effect was due to increased levels of sP-sel. Mice infused with P-sel-Ig showed significantly more fibrin deposited on the luminal face of the injured vessels than control mice. Plasma from ΔCT mice or mice infused with P-sel-Ig contained higher concentration of pro-coagulant microparticles and clotted one minute faster than WT. This pro-coagulant phenotype of ΔCT mice could be reversed by a 4-day treatment with PSGL-Ig, a P-selectin inhibitor. We propose that sP-sel should no longer be considered only as a marker of inflammation or platelet activation, but also as a direct inducer of pro-coagulant activity associated with vascular and thrombotic diseases.
Eumetazoan fossils in terminal Proterozoic phosphorites?
Authors: Xiao Shuhai , Yuan Xunlai , Knoll Andrew H.
Published: July 2002

Phosphatic sedimentary rocks preserve a record of early animal life
different from and complementary to that provided by Ediacaran fossils
in terminal Proterozoic sandstones and shales. Phosphorites of the
Doushantuo Formation, South China, contain eggs, egg cases, and
stereoblastulae that document animals of unspecified phylogenetic
position; small fossils containing putative spicules may specifically
record the presence of sponges. Microfossils recently interpreted as
the preserved gastrulae of cnidarian and bilaterian metazoans can
alternatively be interpreted as conventional algal cysts and/or egg
cases modified by diagenetic processes known to have had a pervasive
influence on Doushantuo phosphorites. Regardless of this
interpretation, evidence for Doushantuo eumetazoans is provided by
millimeter-scale tubes that display tabulation and apical budding
characteristic of some Cnidaria, especially the extinct tabulates. Like
some Ediacaran remains, these small, benthic, colonial fossils may
represent stem-group eumetazoans or stem-group cnidarians that lived in
the late Proterozoic ocean.
Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis.
Authors: Schröder A E , Greiner A , Seyfert C , Berek C
Published: July 2002

In patients with rheumatoid arthritis the synovial membrane of the affected joint is infiltrated with lymphoid cells which may be arranged in structures resembling germinal centers. We have directly isolated such infiltrates to determine whether B-cell clones within them are selected and expanded in a process analogous to that which normally takes place in the germinal centers in secondary lymphoid organs. The data suggest that an antigen-driven process leads to the accumulation of B cells in the synovial membrane. The finding of identical sequences in consecutive sections suggests that under conditions of chronic stimulation, memory B cells may enter a stage of differentiation in which they proliferate without further accumulation of somatic mutations. Further we see intraclonal diversity which underlines the germinal center-like character of these infiltrates and demonstrates that a microenvironment is built up in this nonlymphoid tissue which supports antigen-dependent differentiation of B cells. This is the first demonstration, to our knowledge, of a germinal center-like reaction outside lymphoid tissue.
Multivalent DNA-binding properties of the HMG-1 proteins.
Authors: Maher J F , Nathans D
Published: July 2002

HMG-I proteins are DNA-binding proteins thought to affect the formation and function of transcription complexes. Each protein contains three DNA-binding motifs, known as AT-hooks, that bind in the minor groove of AT tracts in DNA. Multiple AT-hooks within a polypeptide chain should contact multiple AT tracts, but the rules governing these interactions have not been defined. In this study, we demonstrate that high-affinity binding uses two or three appropriately spaced AT tracts as a single multivalent binding site. These principles have implications for binding to regulatory elements such as the interferon beta enhancer, TATA boxes, and serum response elements.
Molecular cloning of a rat chromosome putative recombinogenic sequence homologous to the hepatitis B virus encapsidation signal.
Authors: Aoki H , Kajino K , Arakawa Y , Hino O
Published: July 2002

Previously, we reported that a 61-bp subgenomic HBV DNA sequence (designated as 15AB, nt 1855-1915) is a hot spot for genomic recombination and that a cellular protein binding to 15AB may be the putative recombinogenic protein. In the present study, we established the existence of a 15AB-like sequence in human and rat chromosomal DNA by Southern blot analysis. The 15AB-like sequence isolated from the rat chromosome demonstrated a 80.9% identity with 5'-CCAAGCTGTGCCTTGGGTGGC-3', at 1872-1892 of the hepatitis B virus genome, thought to be the essential region for recombination. Interestingly, this 15AB-like sequence also contained the pentanucleotide motifs GCTGG and CCAGC as an inverted repeat, part of the chi known hot spot for recombination in Escherichia coli. Importantly, a portion of the 15AB-like sequence is homologous (82.1%, 23/28 bp) to break point clusters of the human promyelocytic leukemia (PML) gene, characterized by a translocation [t(15;17)], and to rearranged mouse DNA for the immunoglobulin kappa light chain. Moreover, 15AB and 15AB-like sequences have striking homologies (12/15 = 80.0% and 13/15 = 86.7%, respectively) to the consensus sequence for topoisomerase II. Our present results suggest that this 15AB-like sequence in the rat genome might be a recombinogenic candidate triggering genomic instability in carcinogenesis.