bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy loss of charged projectiles in dusty plasmas
Authors: Nasim M. H. , Mirza Arshad M. , Qaisar M. S. , Murtaza G. , Shukla P. K.
Published: July 2002

The analytical and numerical results for the slowing down of two heavy projectile ions passing through a multicomponent dusty plasma are presented. Within the linear dielectric approach, the electrostatic potential and the stopping power of the two projectiles are computed for different values of KD (the normalized effective wave number) and R (the separation between the two projectiles) retaining two-ion-correlation effects. The enhancement in the energy loss is observed, and it is compared with that of a single ion projectile case. These results are useful to explain the crystallization of dust grains in astrophysical and laboratory plasmas.
Self-consistent plasma-neutral modeling in tokamak plasmas with a large-area toroidal belt limiter
Authors: Gray D. S. , Baelmans M. , Boedo J. A. , Reiter D. , Conn R. W.
Published: July 2002

Plasma-neutral phenomena in the edge plasma and scrape-off layer of the Torus Experiment for Technology Oriented Research [G.H. Wolf and the TEXTOR Team, J. Nucl. Mater. 122&123, 1124 (1984)] with the toroidal belt Advanced Limiter Test (ALT-II) [D.M. Goebel et al., J. Nucl. Mater. 162–164, 115 (1989)] are simulated using the code package B2-EIRENE [D. Reiter et al., Plasma Phys. Controlled Fusion 33, 1579 (1991)]. Spatially-constant, anomalous radial transport coefficients (D,V,χ) are used for fitting measured electron temperature and density profiles. Primary neutral fluxes are determined by plasma fluxes to material surfaces, and Dα emissions are predicted from them. Comparison of the predicted Dα emission with measurements indicates a critical need, in predictive modeling, for a self-consistent model of fluxes to material surfaces that are parallel to the magnetic field. Appropriate factors are calculated for deducing D+ source rates from Dα emissions measured in various locations, taking into account molecular processes and spatially varying plasma parameters; values range from 17 to 28 ions/photon. Ion fluxes lost to pumps or the wall must be explicitly re-introduced as neutral fluxes at the outer boundary.
Systematic solution of the Vlasov–Poisson equations for charged particle beams
Authors: Channell Paul J.
Published: July 2002

Rapidly oscillating solutions of the Vlasov–Poisson equations are required when external forces are rapidly oscillating, as occurs in focusing systems for charged particle beams. Such systems are treated using a Hamiltonian averaging technique carried out to third order. As a result one can deal with the problems of matching, stability, and transient time evolution using the well-established techniques previously used for simpler, time-independent systems.
Generation of wakefields by elliptically polarized laser pulses in a magnetized plasma
Authors: Shukla P. K.
Published: July 2002

It is shown that elliptically polarized short laser pulses in a magnetized plasma can generate upper-hybrid wakefields. The potential profiles of the latter are obtained for given laser beam envelopes. The upper-hybrid wakefields can accelerate electrons to high energy due to the surfatron process.
Magnetohydrodynamic turbulence in the solar wind
Authors: Goldstein Melvyn L. , Roberts D. Aaron
Published: July 2002

Low frequency fluctuations in the solar wind magnetic field and plasma velocity are often highly correlated, so much so that the fluctuations may be thought of as originating near the Sun as nearly perfect Alfvén waves. Power spectra of these fluctuations from 10−7 Hz to several Hz to suggest that the medium is turbulent. Near 1 AU, fluctuations below 10−5 Hz have a relatively flat slope (∼−1) and contain most of the energy in the fluctuating fields. From 10−5 Hz to ∼0.1 Hz, the spectra exhibit a power law inertial range similar to that seen in ordinary fluid turbulence. At the highest frequencies, the rapid fall-off of the power suggests that strong dissipation is occurring. From in situ measurements, it is clear that the fluctuations emanate from the solar corona. The turbulent cascade appears to evolve most rapidly in the vicinity of velocity shears and current sheets. Numerical solutions of both the compressible and incompressible equations of magnetohydrodynamics in both Cartesian and spherical geometry corroborate this interpretation. There are conflicting interpretations of observations suggesting that much of the power in magnetic field fluctuations resides in quasi-two-dimensional structures and simulations have helped to elucidate some of these issues.
Ion flow driven by waves in the ion cyclotron frequency range
Authors: Weitzner Harold , Berry Lee A. , Jaeger E. Fred , Batchelor Donald B.
Published: July 2002

An ion kinetic equation is solved by expansion in a parameter corresponding to the small parameter of neoclassical transport theory and the small parameter of geometrical optics. A slab model with perpendicular stratification of the magnetic field is assumed, and a given rf (radio frequency) field is present with a frequency corresponding to a modest multiple of the ion cyclotron frequency. The rf induced ion flow perpendicular to the magnetic field is calculated. The parallel flow may be large, but it cannot be calculated without an analysis of the electron transport.
Tilt mode stability scaling in field-reversed configurations with finite Larmor radius effect
Authors: Iwasawa Naotaka , Ishida Akio , Steinhauer Loren C.
Published: July 2002

The marginal stability of a static plasma with finite-Larmor-radius (FLR) effects depends on a combination of the FLR effect and the ideal magnetohydrodynamic (MHD) potential energy. For the tilt mode in a field-reversed configuration (FRC) previous computations of these two factors led to a prediction of stability for S*⩽(3−5)E where S* is the macroscale parameter (separatrix radius/ion skin depth) and E is the elongation (separatrix half length/separatrix radius). This prediction explained the observed stability of most experiments. However, recent computations of actual MHD eigenfunctions indicate that the MHD growth rate has a much weaker scaling with elongation than previously believed. As a consequence, most of the long-lived, stable FRC experiments lie in the region predicted to be unstable. It appears then that the stability of FRC experiments is not explained by FLR effects in a static equilibrium.
Experiment and modeling of an atmospheric pressure arc in an applied oscillating magnetic field
Authors: Karasik Max , Roquemore A. L. , Zweben S. J.
Published: July 2002

A set of experiments are carried out to measure and understand the response of a free-burning atmospheric pressure carbon arc to applied transverse dc and ac magnetic fields. The arc is found to deflect parabolically for the dc field and assumes a growing sinusoidal structure for the ac field. A simple analytic two-parameter fluid model of the arc dynamics is derived, in which the arc response is governed by the arc jet originating at the cathode, with the applied J×B force balanced by inertia. Time variation of the applied field allows evaluation of the parameters individually. A fit of the model to the experimental data gives a value for the average jet speed an order of magnitude below Maecker’s estimate of the maximum jet speed [H. Maecker, Z. Phys. 141, 198 (1955)]. An example industrial application of the model is considered.
Magnetically induced pulser laser excitation
Authors: Taylor R. S. , Leopold K. E.
Published: July 2002

A novel excitation scheme has been developed for excimer discharge lasers. The technique uses pulse transformer technology to induce a fast, high voltage pulse directly onto a ground potential laser electrode resulting in the breakdown of the laser gas mix. Saturation of the pulse transformer core inductance then permits efficient energy transfer from the main energy storage circuit into the discharge. When this excitation technique was used in a XeCl laser an output energy density of 2.5 J/l and an overall electrical to optical efficiency of 2% were obtained. The technique appears promising for the development of high energy, high average power excimer lasers.
Improvement of optical characteristics of Al0.48In0.52As grown by molecular beam epitaxy
Authors: Welch D. F. , Wicks G. W. , Eastman L. F. , Parayanthal P. , Pollak F. H.
Published: July 2002

The photoluminescence linewidth (4 K) of Al0.48In0.52As was reduced to 15 meV and its dependence was determined to be a strong function of the substrate temperature and As4 overpressure. Raman spectroscopy correlates the luminescence broadening to the crystallinity of the AlInAs. The ratio of the allowed longitudinal optical phonon to forbidden transverse optical phonon Raman peak heights is 10:1.
Electron and hole impact ionization coefficients in GaAs-AlxGa1−xAs superlattices
Authors: Juang F-Y. , Das U. , Nashimoto Y. , Bhattacharya P. K.
Published: July 2002

Electron and hole multiplication and impact ionization coefficients have been measured with pure carrier injection in p+-n−-n+ and p+-n diodes grown by molecular beam epitaxy. Values of the electron and hole ionization coefficient ratio α/β=2–5 are measured for superlattices with well width Lz≥100 Å and α/β>10 is measured in a graded band-gap superlattice with a total well and barrier width LB+LZ=120 Å. The ratio decreases and becomes less than unity for smaller well sizes. This is caused by an increase in β(E) while α(E) remains fairly constant. The results have been interpreted by considering varying hole confinement and scattering in the coupled quantum wells.
Limited reaction processing: Silicon epitaxy
Authors: Gibbons J. F. , Gronet C. M. , Williams K. E.
Published: July 2002

We introduce a new technique, limited reaction processing, in which radiant heating is used to provide rapid, precise changes in the temperature of a substrate to control surface reactions. This process was used to fabricate thin layers of high quality epitaxial silicon. Abrupt transitions in doping concentration at the epitaxial layer/substrate interface were achieved for undoped films deposited on heavily doped substrates.
Differential surface photovoltage measurement of minority-carrier diffusion length in thin films
Authors: Schwarz R. , Slobodin D. , Wagner S.
Published: July 2002

A new surface photovoltage technique is introduced for the determination of the minority-carrier diffusion length in thin semiconductor films. The technique eliminates the effect of a back surface barrier on the measurement by separating out the back barrier contribution to the total photovoltage signal. With a direct difference method based on a double lock-in technique, the measurement can be carried out in a single run.
Quantitative photoelastic measurement of residual strains in undoped semi-insulating gallium arsenide
Authors: Yamada Masayoshi
Published: July 2002

A new quantitative photoelastic method has been developed to measure residual strains in undoped semi-insulating (001) GaAs substrates for integrated circuits. The absolute values of the shear strain ‖exy‖ and the difference of the expansion and contraction strains ‖eyy−exx‖ existing in the (001) substrate plane are quantitatively determined by using the present method. Their two-dimensional distribution maps are demonstrated to exhibit fourfold symmetries rotating 45° to each other. The absolute values are found to be of the order of 10−5 at the substrate edges.
Z-pinch implosions onto extremely low-density foam cylinders
Authors: Spielman R. B. , Matzen M. K. , Palmer M. A. , Rand P. B. , Hussey T. W. , McDaniel D. H.
Published: July 2002

We have imploded xenon gas-puff Z pinches onto small diameter, extremely low-density foam cylinders ( ρ=0.0045 g/cm3). The presence of the foam on the cylindrical axis had little effect on the radiation production efficiency, pulse width, or spectral details, but it significantly improved the symmetry and uniformity of the stagnation. These experiments confirm that we can stagnate and thermalize a high velocity (5×107 cm/s) plasma onto a cold, low-density target and suggest the feasibility of creating a homogeneous plasma for x-ray laser studies.
Structure and bonding at the CaF2/Si (111) interface
Authors: Himpsel F. J. , Hillebrecht F. U. , Hughes G. , Jordan J. L. , Karlsson U. O. , McFeely F. R. , Morar J. F. , Rieger D.
Published: July 2002

High resolution core level spectroscopy with synchrotron radiation is used to determine the bonding at the epitaxial CaF2/Si (111) interface. It is found that both Ca and F bond to Si at the interface inducing core level shifts of +0.4 eV and −0.8 eV, respectively. Structural models with an atomically sharp interface are proposed where Ca bonds to the first layer Si and F to the second layer.
Formation of (100)GaAs on (100) silicon by laser recrystallization
Authors: Christou A. , Efthimiopoulos T. , Kiriakidis G. , Varmazis C.
Published: July 2002

Epitaxial growth of (100) GaAs on (100) silicon was achieved by excimer laser annealing of amorphous GaAs layers at 248 nm. An AlAs encapsulation layer was found to be necessary to prevent the loss of arsenic during laser annealing. An energy density of 105 mJ/cm2 was the critical energy density for recrystallization. Field-effect transistors were fabricated on the regrown (100) GaAs and resulted in a transconductance of 70–80 ms/mm.
Zn diffusion in InP: Effect of substrate dopant concentration
Authors: Serreze H. B. , Marek H. S.
Published: July 2002

We have performed open-tube diffusion of Zn into n-type InP over the temperature range 525–675 °C. For heavily doped InP, the observed diffusion profiles are consistent with an interstitial-substitutional model where the interstitial Zn is doubly ionized. However, for undoped InP the profiles have a significantly different shape and the diffusion is deeper. Assumption of neutral interstitial Zn is able to account for these two changes. A tentative model is proposed to explain the dependence of the interstitial Zn ionization state on the starting substrate dopant concentration.
Optical characterization of InGaAs-InAlAs strained-layer superlattices grown by molecular beam epitaxy
Authors: Nishi Kenichi , Hirose Kazuyuki , Mizutani Takashi
Published: July 2002

InGaAs-InAlAs strained-layer superlattices, with both controlled strain magnitude and direction in the narrower gap layers, were grown by molecular beam epitaxy. Exciton related peaks and steplike structures in transmission spectra were clearly observed even at room temperature. The close agreement of these observed peak positions with theoretical calculations indicates that heavy-hole and light-hole level reversal was attained in the tensile-strained narrower gap layers.
Carbon incorporation in metalorganic chemical vapor deposition (Al,Ga)As films grown on (100), (311)A, and (311)B oriented GaAs substrates
Authors: Tamamura K. , Ogawa J. , Akimoto K. , Mori Y. , Kojima C.
Published: July 2002

The amount of carbon in GaAs and (Al,Ga)As films depends on the orientation of crystals grown by metalorganic chemical vapor deposition. We investigated the relation between the incorporation of carbon and the orientation of crystals using (100), (311)A, and (311)B substrates. The concentration of electrons on (311)B substrates of unintentionally doped films was higher than those of the films on (100) and (311)A substrates. The films grown on (311)B substrates did not show p-type behavior even when they were grown with a fairly low V/III ratio. The relative intensity of the free-to-carbon acceptor luminescence of the films grown on (311)B substrates was smaller than that of films grown on the other substrates. This is consistent with the results of carbon contamination indicated by secondary ion mass spectra. Furthermore, a reduced peak in photoluminescence caused by defects was observed when (311)B substrates were used.
Use of tertiarybutylarsine in the metalorganic chemical vapor deposition growth of GaAs
Authors: Lum R. M. , Klingert J. K. , Lamont M. G.
Published: July 2002

Epitaxial films of GaAs have been grown by metalorganic chemical vapor deposition using a new arsenic source, tertiarybutylarsine (TBAs). Films with excellent surface morphology were obtained for low V/III values over a wide temperature range (600–800 °C), and relatively strong free-exciton emission was observed in the photoluminescence spectra. Hall measurements indicate carrier concentrations as low as 5×1015 cm−3 and mobilities μ300=4000 cm2/V s. These are equivalent or better than results obtained with trimethylarsenic. In contrast to growth with arsine, the layers were found to be n type for all values of V/III ratio investigated (2–20). Higher quality layers can be expected with source repurification of synthesis via a purer chemical process.
Correlation of trap creation with electron heating in silicon dioxide
Authors: DiMaria D. J.
Published: July 2002

Electron trap creation in thin films of silicon dioxide is shown to follow the electron heating characteristic of this material. No trap creation is observed in the near-thermal transport regime at electric field magnitudes less than 1.5 MV/cm. At these low fields, electrons travel in a streaming fashion close to the bottom of the oxide conduction band at energies less than that of the dominant optical phonon mode at 0.153 eV. At higher electric fields, the rate of bulk trap creation is proportional to the average energy of the hot electrons which move in a dispersive manner and can reach energies as large as 4 eV. Also, interface charge and interface state buildup are observed to be proportional to electron capture into bulk traps in the as-fabricated oxides or into those induced by the passage of hot electrons.
Electron velocity and negative differential mobility in AlGaAs/GaAs modulation-doped heterostructures
Authors: Masselink W. T. , Braslau N. , Wang W. I. , Wright S. L.
Published: July 2002

We have measured the electron velocity in low-doped GaAs and in AlGaAs/GaAs modulation-doped heterostructures at electric fields up to 8000 V/cm at both 300 and 77 K. In order to avoid the charge domain formation which occurs in dc measurements at these fields, this measurement uses 35 GHz radiation to supply the electric field. These measurements indicate that the peak velocity for electrons in the heterostructures is lower than for electrons in bulk low-doped GaAs. This result is explained in terms of modified intervalley transfer, real space transfer, and an enhanced scattering with polar optical phonons.
Dynamics of exciton transfer between monolayer-flat islands in single quantum wells
Authors: Deveaud Benoit , Damen T. C. , Shah Jagdeep , Tu C. W.
Published: July 2002

We have studied the transfer dynamics of excitons between large, monolayer-flat islands in single quantum wells, using subpicosecond luminescence spectroscopy. We show that the excitons transfer from the narrow to the wide regions of the well in ∼250 ps.
Luminescence of heteroepitaxial zinc oxide
Authors: Bethke S. , Pan H. , Wessels B. W.
Published: July 2002

Thin layers of ZnO were grown on (0001) oriented sapphire by organometallic chemical vapor deposition. Low-temperature photoluminescence indicates that near-band-edge luminescence dominates the spectrum. In contrast to bulk grown material deep level luminescence for the layers is relatively weak.
Capture of electrons and holes in quantum wells
Authors: Deveaud Benoit , Shah Jagdeep , Damen T. C. , Tsang W. T.
Published: July 2002

The capture of electrons and holes by quantum wells in multiple quantum well samples of InGaAs/InP is investigated using subpicosecond luminescence spectroscopy. For samples with thin barriers, quantum capture or carrier thermalization dominates. For thicker barriers (>500 Å), transport of carriers to the well dominates. We show that quantum capture time is <0.3 ps for holes and <1 ps for electrons. No significant dependence on well thickness is observed. Finally, Coulomb interaction between electrons and holes is shown to ‘‘trap’’ the electrons in unbound states in InGaAs before they are captured by the well.
Influence of the applied field frequency (27–2450 MHz) in high-frequency sustained plasmas used to etch polyimide
Authors: Sauvé G. , Moisan M. , Paraszczak J. , Heidenreich J.
Published: July 2002

The effect of the plasma stimulating frequency upon the etching of polyimide is reported. For the first time, a system has been developed which generates, over a large frequency domain (27–2450 MHz), a high-frequency (HF) produced plasma by identical means (surface wave propagation) in a fixed plasma volume. It is found that the addition of CF4 to an O2 plasma affects the etch rate of polyimide in a manner which depends upon the operating frequency of the HF plasma. In particular, a maximum of etch rate per watt is observed around 50 MHz.
Deuterium isotope effect on the intramolecular electron transfer inPseudomonas aeruginosaazurin
Authors: Farver Ole , Zhang Jingdong , Chi Qijin , Pecht Israel , Ulstrup Jens
Published: July 2002

Intramolecular electron transfer in azurin in water and deuterium oxide has been studied over a broad temperature range. The kinetic deuterium isotope effect,kH/kD, issmallerthan unity (0.7 at 298 K), primarily caused by the different activation entropies in water (−56.5 J K−1mol−1) and in deuterium oxide (−35.7 J K−1mol−1). This difference suggests a role for distinct protein solvation in the two media, which is supported by the results of voltammetric measurements: the reduction potential (E0′) of Cu2+/+at 298 K is 10 mV more positive in D2O than in H2O. The temperature dependence ofE0′is also different, yielding entropy changes of −57 J K−1mol−1in water and −84 J K−1mol−1in deuterium oxide. The driving force difference of 10 mV is in keeping with the kinetic isotope effect, but the contribution to ΔS‡from the temperature dependence ofE0′ispositiverather than negative. Isotope effects are, however, also inherent in the nuclear reorganization Gibbs free energy and in the tunneling factor for the electron transfer process. A slightly larger thermal protein expansion in H2O than in D2O (0.001 nm K−1) is sufficient both to account for the activation entropy difference and to compensate for the different temperature dependencies ofE0′. Thus, differences in driving force and thermal expansion appear as the most straightforward rationale for the observed isotope effect.
Can medial temporal lobe regions distinguish true from false? An event-related functional MRI study of veridical and illusory recognition memory
Authors: Cabeza Roberto , Rao Stephen M. , Wagner Anthony D. , Mayer Andrew R. , Schacter Daniel L.
Published: July 2002

To investigate the types of memory traces recovered by the medial temporal lobe (MTL), neural activity during veridical and illusory recognition was measured with the use of functional MRI (fMRI). Twelve healthy young adults watched a videotape segment in which two speakers alternatively presented lists of associated words, and then the subjects performed a recognition test including words presented in the study lists (True items), new words closely related to studied words (False items), and new unrelated words (New items). The main finding was a dissociation between two MTL regions: whereas the hippocampus was similarly activated for True and False items, suggesting the recovery of semantic information, the parahippocampal gyrus was more activated for True than for False items, suggesting the recovery of perceptual information. The study also yielded a dissociation between two prefrontal cortex (PFC) regions: whereas bilateral dorsolateral PFC was more activated for True and False items than for New items, possibly reflecting monitoring of retrieved information, left ventrolateral PFC was more activated for New than for True and False items, possibly reflecting semantic processing. Precuneus and lateral parietal regions were more activated for True and False than for New items. Orbitofrontal cortex and cerebellar regions were more activated for False than for True items. In conclusion, the results suggest that activity in anterior MTL regions does not distinguish True from False, whereas activity in posterior MTL regions does.
Sex-ratio conflicts, kin selection, and the evolution of altruism
Authors: Alonso Wladimir J. , Schuck-Paim Cynthia
Published: July 2002

Kin-selection theory has thrived in the explanation of a wide variety of biological phenomena, chiefly the evolution of biological altruism as that found in sterile castes of eusocial insects. Much of the way in which it has been tested is based on the existence of conflicts over sex-ratio production within eusocial colonies. However, despite neatly showing eusocial colonies as arenas where selection at the gene level triggers the appearance of sophisticated disputes, these studies have only demonstrated the existence of genes that act by biasing sex ratios to promote their own spread. Here we argue that such genes depend on the social organization of the colonies where they are expressed, but that they are not, in any way, the precursors of these societies—the major implication being that unequivocal evidence that eusociality evolved through the action of kin-selected altruistic genes is still lacking. Additionally, we highlight the neglect of alternative theories on the explanation of both biological altruism and sex-ratio conflicts, and defend that the enthusiasm with the latter has, in some cases, led to its inappropriate use as a basis for the explanation of other biological characteristics of eusocial organisms, when accounts based on phylogenetic or physiological constraints are also available.
Intron presence–absence polymorphism in
Drosophila
driven by positive Darwinian selection
Authors: Llopart Ana , Comeron Josep M. , Brunet Frédéric G. , Lachaise Daniel , Long Manyuan
Published: July 2002

Comparisons of intron–exon structures between homologous genes in different eukaryotic species have revealed substantial variation in the number of introns. These observations imply that, in each case, an intron presence–absence polymorphism must have existed in the past. Such a polymorphism, created by a recent intron-loss mutation, is reported here in a eukaryotic organism. This gene structure, detected in the
jingwei
(
jgw
) gene, segregates at high frequency (77%) in natural populations of
Drosophila teissieri
and is associated with a marked change in mRNA levels. Furthermore, the intron loss does not result from a mRNA-mediated mechanism as is usually proposed, but from a partial deletion at the DNA level that also results in the addition of four new amino acids to the
JGW
protein. Population genetic analyses of the pattern of nucleotide variation surrounding the intron polymorphism indicate the action of positive Darwinian selection on the intron-absent variant. Forward simulations suggest that the intensity of this selection is weak to moderate, roughly equal to the selection intensity on most replacement mutations in
Drosophila
.
Transcription-coupled repair in yeast is independent from ubiquitylation of RNA pol II: Implications for Cockayne's syndrome
Authors: Lommel Lori , Bucheli Miriam E. , Sweder Kevin S.
Published: July 2002

Cockayne's syndrome cells lack transcription-coupled nucleotide excision repair (TCR) and ubiquitylation of RNA polymerase II large subunit (RNA pol II LS), suggesting that ubiquitylation of RNA pol II LS may be necessary for TCR in eukaryotes. Rsp5 is the sole yeast ubiquitin-protein ligase that ubiquitylates RNA pol II LS in cells exposed to DNA-damaging agents. In yeast lacking functional Rsp5, there is no ubiquitylation of RNA pol II LS. We show here that removal, repression, or over-expression of Rsp5 has no effect on TCR, demonstrating that ubiquitylation of the RNA pol II LS is not required for TCR. We infer that the lack of ubiquitylation of RNA pol II LS in Cockayne's syndrome cells does not cause their defect in TCR.
Histone deacetylase inhibitor selectively induces p21
WAF1
expression and gene-associated histone acetylation
Authors: Richon Victoria M. , Sandhoff Todd W. , Rifkind Richard A. , Marks Paul A.
Published: July 2002

Histone deacetylases (HDACs) catalyze the removal of acetyl groups on the amino-terminal lysine residues of core nucleosomal histones. This activity is associated generally with transcriptional repression. We have reported previously that inhibition of HDAC activity by hydroxamic acid-based hybrid polar compounds, such as suberoylanilide hydroxamic acid (SAHA), induces differentiation and/or apoptosis of transformed cells
in vitro
and inhibits tumor growth
in vivo
. SAHA is a potentially new therapeutic approach to cancer treatment and is in Phase I clinical trials. In several tumor cell lines examined, HDAC inhibitors alter the expression of less than 1% of expressed genes, including the cell cycle kinase inhibitor p21
WAF1
. In T24 bladder carcinoma cells, SAHA induces up to a 9-fold increase in p21
WAF1
mRNA and protein, which is, at least in part, because of an increase in the rate of transcription of the gene. SAHA causes an accumulation of acetylated histones H3 and H4 in total cellular chromatin by 2 h, which is maintained through 24 h of culture. An increase in the accumulation of acetylated H3 and H4 was detected throughout the p21
WAF1
promoter and the structural gene after culture with SAHA. The level of histone acetylation did not change in chromatin associated with the actin and p27 genes, and their mRNA expression was not altered during culture of T24 cells with SAHA. Thus, the present findings indicate that the induction of p21
WAF1
by SAHA is regulated, at least in part, by the degree of acetylation of the gene-associated histones and that this induced increase in acetylation is gene selective.
Control of
Drosophila
perineurial glial growth by interacting neurotransmitter-mediated signaling pathways
Authors: Yager James , Richards Stephen , Hekmat-Scafe Daria S. , Hurd Daryl D. , Sundaresan Vanathi , Caprette David R. , Saxton William M. , Carlson John R. , Stern Michael
Published: July 2002

Drosophila
peripheral nerves, similar structurally to the peripheral nerves of mammals, comprise a layer of axons and inner glia, surrounded by an outer perineurial glial layer. Although it is well established that intercellular communication occurs among cells within peripheral nerves, the signaling pathways used and the effects of this signaling on nerve structure and function remain incompletely understood. Here we demonstrate with genetic methods that the
Drosophila
peripheral nerve is a favorable system for the study of intercellular signaling. We show that growth of the perineurial glia is controlled by interactions among five genes:
ine
, which encodes a putative neurotransmitter transporter;
eag
, which encodes a potassium channel;
push
, which encodes a large, Zn
2+
-finger-containing protein;
amn
, which encodes a putative neuropeptide related to the pituitary adenylate cyclase activator peptide; and
NF1
, the
Drosophila
ortholog of the human gene responsible for type 1 neurofibromatosis. In other
Drosophila
systems,
push
and
NF1
are required for signaling pathways mediated by Amn or the pituitary adenylate cyclase activator peptide. Our results support a model in which the Amn neuropeptide, acting through Push and NF1, inhibits perineurial glial growth, whereas the substrate neurotransmitter of Ine promotes perineurial glial growth. Defective intercellular signaling within peripheral nerves might underlie the formation of neurofibromas, the hallmark of neurofibromatosis.
Functional switching of GABAergic synapses by ryanodine receptor activation
Authors: Sun Miao-Kun , Nelson Thomas J. , Alkon Daniel L.
Published: July 2002

The role of the ryanodine receptor (RyR) in modifiability of synapses made by the basket interneurons onto the hippocampal CA1 pyramidal cells was examined in rats. Associating single-cell RyR activation with postsynaptic depolarization increased intracellular free Ca2+concentrations and reversed the basket interneuron–CA1 inhibitory postsynaptic potential into an excitatory postsynaptic potential. This synaptic transformation was accompanied by a shift of the reversal potential from that of chloride toward that of bicarbonate. This inhibitory postsynaptic potential–excitatory postsynaptic potential transformation was prevented by blocking RyR or carbonic anhydrase. Associated postsynaptic depolarization and RyR activation, therefore, changes GABAergic synapses from excitation filters to amplifier and, thereby, shapes information flow through the hippocampal network.
Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors
Authors: Champagne Frances , Diorio Josie , Sharma Shakti , Meaney Michael J.
Published: July 2002

Naturally occurring variations in maternal licking/grooming influence neural development and are transmitted from mother to female offspring. We found that the induction of maternal behavior in virgin females through constant exposure to pups (pup sensitization) was significantly shorter in the offspring of High compared with Low licking/grooming mothers, suggesting differences in maternal responsivity. In randomly selected females screened for individual differences in maternal responsivity and subsequently mated, there was a significant and negative correlation (
r
= −0.73) between the latency to exhibit maternal behavior in the pup sensitization paradigm and the frequency of pup licking/grooming during lactation. Females that were more maternally responsive to pups and that showed increased levels of pup licking/grooming also showed significantly higher oxytocin receptor levels in the medial preoptic area, the lateral septum, the central nucleus (n.) of the amygdala, the paraventricular n. of the hypothalamus, and the bed n. of the stria terminalis. Intracerebroventricular administration of an oxytocin receptor antagonist to mothers on postpartum day 3 completely eliminated the differences in pup licking/grooming, suggesting that differences in oxytocin receptor levels are functionally related to maternal behavior. Finally, estrogen treatment of virgin females significantly increased oxytocin receptor binding in the medial preoptic area and lateral septum of female offspring of High, but not Low, licking/grooming mothers. These findings suggest that maternal licking/grooming influences the development of estrogen sensitivity in brain regions that regulate maternal behavior, providing a potential mechanism for the intergenerational transmission of individual differences in maternal behavior.
The molecular role of the common gamma c subunit in signal transduction reveals functional asymmetry within multimeric cytokine receptor complexes.
Authors: Lai S Y , Xu W , Gaffen S L , Liu K D , Longmore G D , Greene W C , Goldsmith M A
Published: July 2002

The specific signal transduction function of the gamma c subunit in the interleukin (IL) 2, IL-4, IL-7, IL-9, and IL-15 receptor complexes remains undefined. The present structure-function analyses demonstrated that the entire cytoplasmic tail of gamma c could be functionally replaced in the IL-2 receptor (IL-2R) signaling complex by a severely truncated erythropoietin receptor cytoplasmic domain lacking tyrosine residues. Heterodimerization of IL-2R beta with either gamma c or the truncated erythropoietin receptor chain led to an array of specific signals normally derived from the native IL-2R despite the substitution of Janus kinase JAK2 for JAK3 in the receptor complex. These findings thus suggest a model in which the gamma c subunit serves as a common and generic "trigger" chain by providing a nonspecific Janus kinase for signaling program initiation, while signal specificity is determined by the unique "driver" subunit in each of the gamma c- containing receptor complexes. Furthermore, these results may have important functional implications for the asymmetric design of many cytokine receptor complexes and the evolutionary design of receptor subfamilies that share common trigger or driver subunits.
Endothelin-B receptor is expressed by neural crest cells in the avian embryo.
Authors: Nataf V , Lecoin L , Eichmann A , Le Douarin N M
Published: July 2002

Disruptions of the genes encoding endothelin 3 (EDN3) and its receptor endothelin-B receptor (EDNRB) in the mouse result in defects of two neural crest (NC)-derived lineages, the melanocytes, and the enteric nervous system. To assess the mechanisms through which the EDN3/EDNRB signaling pathway can selectively act on these NC derivatives, we have studied the spatiotemporal expression pattern of the EDNRB gene in the avian embryo, a model in which NC development has been extensively studied. For this purpose, we have cloned the quail homologue of the mammalian EDNRB cDNA. EDNRB transcripts are present in NC cells before and during their emigration from the neural tube at all levels of the neuraxis. At later developmental stages, the receptor remains abundantly expressed in the peripheral nervous system including the enteric nervous system. In a previous study, we have shown that EDN3 enhances dramatically the proliferation of NC cells when they are at the pluripotent stage. We propose that the selective effect of EDN3 or EDNRB gene inactivation is due to the fact that both melanocytes and enteric nervous system precursors have to colonize large embryonic areas (skin and bowel) from a relatively small population of precursors that have to expand considerably in number. It is therefore understandable that a deficit in one of the growth-promoting pathways of NC cells has more deleterious effects on long-range migrating cells than on the NC derivatives which develop close to the neural primordium like the sensory and sympathetic ganglia.
Immunocytochemical localization of the endogenous neuroexcitotoxin quinolinate in human peripheral blood monocytes/macrophages and the effect of human T-cell lymphotropic virus type I infection.
Authors: Venkateshan C N , Narayanan R , Espey M G , Moffett J R , Gajdusek D C , Gibbs C J , Namboodiri M A
Published: July 2002

Quinolinate (Quin), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that appears to act through the N-methyl-D-aspartate receptor system, was localized in cultured human peripheral blood monocytes/macrophages (PBMOs) by using a recently developed immunocytochemical method. Quin immunoreactivity (Quin-IR) was increased in gamma interferon (IFN-gamma)-stimulated monocytes/macrophages (MOs). In addition, the precursors, tryptophan and kynurenine, significantly increased Quin-IR. Infection of MOs by human T-cell lymphotropic virus type I (HTLV-I) in vitro substantially increased both the number of Quin-IR cells and the intensity of Quin-IR. At the peak of the Quin-IR response, about 40% of the cells were Quin-IR positive. In contrast, only about 2-5% of the cells were positive for HTLV-I, as detected by both immunofluorescence for the HTLV-I antigens and PCR techniques for the HTLV-I Tax gene. These results suggest that HTLV-I-induced Quin production in MOs occurs by an indirect mechanism, perhaps via cytokines produced by the infection but not directly by the virus infection per se. The significance of these findings to the neuropathology of HTLV-I infection is discussed.
Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2
Authors: Furuta Machi , Yano Hideki , Zhou An , Rouillé Yves , Holst Jens J. , Carroll Raymond , Ravazzola Mariella , Orci Lelio , Furuta Hiroto , Steiner Donald F.
Published: July 2002

The prohormone convertase SPC2 (PC2) participates in the processing of proinsulin, proglucagon, and a variety of other neuroendocrine precursors, acting either alone or in conjunction with the structurally related dense-core granule convertase SPC3 (PC3/PC1). We have generated a strain of mice lacking active SPC2 by introducing the neomycin resistance gene (Neo
r
) into the third exon of the mSPC2 gene. This gene insertion results in the synthesis of an exon 3-deleted form of SPC2 that does not undergo autoactivation and is not secreted. The homozygous mutant mice appear to be normal at birth. However, they exhibit a small decrease in rate of growth. They also have chronic fasting hypoglycemia and a reduced rise in blood glucose levels during an intraperitoneal glucose tolerance test, which is consistent with a deficiency of circulating glucagon. The processing of proglucagon, prosomatostatin, and proinsulin in the alpha, delta, and beta cells, respectively, of the pancreatic islets is severely impaired. The islets in mutant mice at 3 months of age show marked hyperplasia of alpha and delta cells and a relative diminution of beta cells. SPC2-defective mice offer many possibilities for further delineating neuroendocrine precursor processing mechanisms and for exploring more fully the physiological roles of many neuropeptides and peptide hormones.
DNA damage-dependent transcriptional arrest and termination of RNA polymerase II elongation complexes in DNA template containing HIV-1 promoter
Authors: Wang Zhuying , Rana Tariq M.
Published: July 2002

We have developed a new biochemical method to isolate a homogeneous population of RNA polymerase II (RNA pol II) elongation complexes arrested at a DNA damage site. The method involves triple-helix formation at a predetermined site in DNA template with a third strand labeled with psoralen at its 5′-end and a biotin at the 3′-end. After triplex formation and near-ultraviolet irradiation (360 nm), DNA templates modified with psoralen were immobilized on streptavidin-coated magnetic beads and used for
in vitro
transcription reactions with HeLa nuclear extracts. Separation of magnetic beads from solution results in isolation of arrested elongation complexes on the immobilized DNA templates. We have applied the method to arrest RNA pol II elongation complexes on a DNA template containing HIV-1 promoter. Our results indicate that psoralen crosslink in the template strand efficiently arrests elongation complexes, and psoralen monoadducts terminate transcription. Our results also demonstrate that a triple-helical structure stabilized by an intercalator, acridine, attached to the third strand of the helix inhibits transcription by a termination pathway. Isolation of stable RNA pol II elongation complexes arrested at DNA damage sites is a remarkable finding. This result demonstrates that arrested elongation complexes are impervious to DNA damage repair machinery and other regulatory proteins present in HeLa nuclear extracts. The method of delivering site-specific psoralen damage by a triplex structure and isolation of arrested RNA pol II elongation complexes should be generalizable to any promoter and DNA template sequences. This strategy provides a new approach to study the mechanism of transcription elongation and transcription-coupled DNA damage repair.
In vitroscanning saturation mutagenesis of an antibody binding pocket
Authors: Burks Elizabeth A. , Chen Gang , Georgiou George , Iverson Brent L.
Published: July 2002

We have combined PCR mutagenesis within vitrotranscription/translation and ELISA for the rapid generation and characterization of antibody mutants. The PCR products are used directly as the template for thein vitrotranscription/translation reactions and because no cloning steps are required, thein vitrosaturation mutagenesis of one residue can be completed in duplicate within a week by a single investigator.In vitroscanning saturation mutagenesis was used to analyze the role and plasticity of six key contact residues (H:Tyr-33, H:Asn-35, H:Tyr-50, H:Trp-100, L:Val-94, and L:Pro-96) in the binding pocket of a single chain Fv antibody derived from the 26–10 monoclonal antibody. A total of 114 mutant antibodies were produced; all 19 substitutions at each of the 6 chosen positions. The mutants were analyzed for binding to digoxin, digitoxin, digoxigenin, and ouabain resulting in the generation of a comprehensive data base of 456 relative affinity values. Excellent agreement between the relative affinity values obtained within vitrosynthesized mutant antibodies and equilibrium affinity data obtained with previously reported purified mutant monoclonal antibodies was observed. Approximately 75% of the single amino acid mutants exhibited significant binding to one or more of the digoxin analogs. Mutations that alter and, in some cases, reverse specificity for the different digoxin analogs were identified.In vitroscanning saturation mutagenesis represents a new tool for protein structure-function and engineering studies and can be interfaced with laboratory automation so that an even higher throughput of protein mutants can be constructed and analyzed.
Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6
Authors: Si Kausik , Chaudhuri Jayanta , Chevesich Jorge , Maitra Umadas
Published: July 2002

Eukaryotic translation initiation factor 6 (eIF6) binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. In this paper, we devised a procedure for purifying eIF6 from rabbit reticulocyte lysates and immunochemically characterized the protein by using antibodies isolated from egg yolks of laying hens immunized with rabbit eIF6. By using these monospecific antibodies, a 1.096-kb human cDNA that encodes an eIF6 of 245 amino acids (calculated
M
r
26,558) has been cloned and expressed in
Escherichia coli
. The purified recombinant human protein exhibits biochemical properties that are similar to eIF6 isolated from mammalian cell extracts. Database searches identified amino acid sequences from
Saccharomyces cerevisiae, Drosophila
, and the nematode
Caenorhabditis elegans
with significant identity to the deduced amino acid sequence of human eIF6, suggesting the presence of homologues of human eIF6 in these organisms.
The partial tandem duplication of
ALL1
in acute myeloid leukemia with normal cytogenetics or trisomy 11 is restricted to one chromosome
Authors: Caligiuri Michael A. , Strout Matthew P. , Oberkircher Adam R. , Yu Feng , de la Chapelle Albert , Bloomfield Clara D.
Published: July 2002

The molecular defects responsible for tumorigenesis in adult
de novo
acute myeloid leukemia (AML) with a normal karyotype or an additional copy of one chromosome (i.e., trisomy) remain largely unknown. We recently discovered that approximately 90% of adult patients with
de novo
AML and trisomy 11 (+11) as a sole abnormality and 11% of adult patients with
de novo
AML and normal cytogenetics carry a molecular rearrangement of the
ALL1
(
MLL, HRX,
or
HTRX
) gene. The rearranged
ALL1
gene has been shown to result from the direct tandem duplication of a portion of
ALL1
itself. To better understand the underlying mechanisms of leukemogenesis, we asked whether in cytogenetically normal cases one or both chromosomes carry the mutated allele and whether in trisomic cases the mutation is present in one, two, or three chromosomes. Herein we show that in cytogenetically normal cases of AML and in cases with +11 as a sole cytogenetic abnormality, only one chromosome contains the mutated
ALL1
allele. Thus a single mutated
ALL1
allele with the partial tandem duplication is sufficient for
ALL1-
associated leukemogenesis, irrespective of the number of normal genes present. The frequently occurring specific association of +11 and
ALL1
gene mutation in the leukemic clone remains unexplained.