bluuebunny/crossref_metadata_2025 huggingface dataset:
Mode transition and nonlinear self-oscillations in the beam-driven collisional discharge plasma
Authors: Lee Hae June , Lee Jae Koo
Published: July 2002

Nonlinear dynamics and self-oscillations in a dc beam-driven collisional discharge are investigated with particle-in-cell simulation and theoretical estimation. Three different modes, anode-glow, temperature-limited, and double-layer modes, are observed in the system. A theory for the critical voltage of mode transition between temperature-limited and anode-glow modes is in good agreement with the simulation results. The mechanism of low frequency self-oscillation in the double layer mode is examined along with period-doubling and chaotic oscillations.
Modeling field ionization in an energy conserving form and resulting nonstandard fluid dynamics
Authors: Mulser P. , Cornolti F. , Bauer D.
Published: July 2002

A fluid model that takes the field ionization energy correctly into account is presented for the first time by introducing an energy conserving ionization current as a source term in the wave equation. Nonstandard type fluid equations result from the finite ejection energy of the electrons in the field ionization process. The energy and momentum distributions of the ejected electrons are obtained from the time-dependent Schrödinger equation and classical Monte Carlo calculations. Characteristic results of how field ionization influences the pulse propagation, and some extremely nonlinear features caused by the ionization current are given.
Theory of two-dimensional mean field electron magnetohydrodynamics
Authors: Das Amita , Diamond P. H.
Published: July 2002

Theoretical studies of mean field electrodynamics for diffusive processes in the electron magnetohydrodynamic (EMHD) model is presented. In contrast to magnetohydrodynamics (MHD), the evolution of the magnetic field here is governed by a nonlinear equation in magnetic field variables. A detailed description of diffusive processes in two dimensions are presented in this paper. In particular, it has been shown analytically that the turbulent magnetic field diffusivity is suppressed from naive quasilinear estimates. It is shown that for complete whistlerization of the spectrum, turbulent diffusivity vanishes. The question of whistlerization of the turbulent spectrum is investigated numerically, and a reasonable tendency towards whistlerization is observed. Numerical studies also show suppression of magnetic field diffusivity in accordance with analytical estimates.
Studies of electronic noise in gyroklystrons
Authors: Calame J. P. , Danly B. G. , Garven M. , Levush B.
Published: July 2002

Direct measurements of phase noise in a four-cavity, 35 GHz gyroklystron producing 50 μs pulses of 175–210 kW output power with 50–53 dB saturated gain are presented. The measurements were performed at a 10.7 MHz frequency offset from the carrier, where the noise is expected to be dominated by shot noise and where the extrinsic noise from the electron gun’s pulsed power supply is manageable. At an operating point with 70 kV beam voltage, 9 A beam current, and a beam velocity ratio of 1.3, a phase noise of −149±1 dBc/Hz was measured during the production of 180 kW output power at 50 dB gain. At a higher beam current of 10 A, the measured phase noise was −146±1 dBc/Hz during production of a 200 kW output power carrier with 53 dB gain. The directly measured phase noise levels were generally within 2–3 dB of the values expected on the basis of carrier-free noise temperature measurements. Overall, the measured gyroklystron noise levels are similar to those of conventional klystrons. Also presented are analytic calculations of the growth rates expected for electrostatic cyclotron instabilities in the region between the electron gun and the input cavity in a previous three-cavity gyroklystron. Very modest perpendicular velocity spreads (rms greater than 2%) are found to completely suppress such noise growth. This lack of significant noise growth above that of bare shot noise is in agreement with experimental results.
Experimental study of laser beam transmission and power accounting in a large scale length laser plasma
Authors: Moody J. D. , MacGowan B. J. , Berger R. L. , Estabrook K. G. , Glenzer S. H. , Kirkwood R. K. , Kruer W. L. , Stone G. E. , Montgomery D. S.
Published: July 2002

It is shown that the measured laser power transmission through a large scale length, high temperature plasma (which emulates an indirect drive ignition-scale plasma) is in approximate agreement with the simulated transmission provided the simulations account for the power loss due to scattering from laser-plasma instabilities. Detailed accounting of the incident, transmitted, scattered, and absorbed powers is used to infer the likely location in the target where most of the scattering occurs along the incident beam trajectory. This location is near the incident laser side of the target at peak electron temperatures for a range of laser intensities. As a result, the backscattered light measurements at peak electron temperature do not require significant adjustment to account for attenuation of the backscattered light as it propagates out through the plasma.
Dynamics of the HCN discharge laser
Authors: Skatrud David D. , De Lucia Frank C.
Published: July 2002

Millimeter/submillimeter rotational absorption techniques are used to monitor the post-discharge decay of vibrational state populations in a gated cw HCN far-infrared discharge laser. The data provide a detailed map of the important energy flow pathways in the laser and make possible the construction and verification of a simple model for the laser excitation and inversion mechanisms. In addition, these data provide the requisite information for the quantification of this model. The resulting predictions are in excellent agreement with our extensive new data set and a substantial body of work reported in the literature.
Time-resolved kinetics of e-h plasma in GaAsP under intense picosecond laser pulse excitation
Authors: Zarrabi H. J. , Wang W. B. , Alfano R. R.
Published: July 2002

Time-resolved photoluminescence kinetics of GaAs1−xPx (x=0.38) were measured by a streak camera system in order to determine the radiative and nonradiative recombination rates. The photoluminescence decay profile was found to be intensity dependent. When excitation power fluence increased above 6×108 W/cm2, the decay profile of emission deviated from exponential form. This is attributed to bimolecular and Auger processes. The bimolecular and Auger rates were determined to be BR=9×10−10 cm3/s and CNR=3×10−29 cm6/s by fitting the time-resolved photoluminescence decay profiles to the solution of the rate equation which describes the dynamical behavior of the photogenerated carriers.
p-n junction formation in InSb and InAs1−xSbx by metalorganic chemical vapor deposition
Authors: Chiang P. K. , Bedair S. M.
Published: July 2002

p-n junctions have been fabricated in InSb and InAs1−xSbx (0.4<x<0.7) using metalorganic chemical vapor deposition. These junctions showed soft breakdown in addition to forward characteristics with a diode factor greater than 2. The ternary alloy has a cut-off wavelength in the 8–11-μm range, thus providing a potential material system for detectors covering the 8–12-μm range.
Image transmission and interferometry with multimode fibers using self-pumped phase conjugation
Authors: Fischer Baruch , Sternklar Shmuel
Published: July 2002

A double-pass image transmission through a single multimode fiber is demonstrated, using a passive phase conjugate mirror. An application to interferometry based on phase sensing is demonstrated, by implementing the multimode fiber and the passive phase conjugate mirror as one arm of a Michelson interferometer. Due to the unique properties of the self-pumped conjugator, nonuniform distortions caused by modal dispersion in the fiber and other aberrations are cancelled out, while uniform phase changes are detected.
Effect of surface treatment on dopant diffusion in polycrystalline silicon capped shallow junction bipolar transistors
Authors: McLaughlin K. L. , Taylor M. A. , Sweeney G.
Published: July 2002

The outdiffusion of boron and arsenic was studied as a function of surface treatment prior to polycrystalline silicon (polysilicon) deposition in the fabrication of bipolar transistors. Secondary ion mass spectrometry and spreading resistance probe analyses were performed to measure boron, arsenic, and concurrent boron-arsenic diffusion after ion implantation and annealing of an undoped (0.25 μm) polysilicon layer. The presence and integrity of an interfacial oxide were examined by Auger electron spectroscopy and transmission electron microscopy. The (20 Å) oxide was found to reduce arsenic diffusion with no effect on boron diffusion. Boron diffusion was reduced in the presence of arsenic and boron was found to reduce arsenic diffusion. The most dramatic reduction in arsenic diffusion occurred when an interfacial oxide and boron were present.
Raman scattering characterization of interface broadening in GaAs/AlAs short period superlattices grown by molecular beam epitaxy
Authors: Jusserand Bernard , Alexandre François , Paquet Daniel , Le Roux Guy
Published: July 2002

We analyze in this letter the Raman scattering spectra on several GaAs/AlAs short period superlattices grown by molecular beam epitaxy with different substrate temperatures and different doping concentrations. The frequency and Raman intensity of both folded acoustical and confined optical phonons, which are observed in all samples, are clearly related to the substrate temperature. These variations: (i) decreasing intensity of the folded acoustical modes, (ii) frequency shift of the optical modes confined in GaAs, are successfully analyzed in terms of interface broadening. A quantitative estimation of the interface widths is obtained and analyzed.
Semi-insulator-embedded InGaAsP/InP flat-surface buried heterostructure laser
Authors: Tanaka K. , Hoshino M. , Wakao K. , Komeno J. , Ishikawa H. , Yamakoshi S. , Imai H.
Published: July 2002

A new structure semi-insulator-embedded flat-surface buried heterostructure 1.3 μm InGaAsP/InP laser has been developed using chloride vapor phase epitaxy. cw threshold currents as low as 18 mA and high-temperature cw operation up to 100 °C have been obtained. Small-signal response above 4 GHz has been achieved and no remarkable roll-off has been observed, which is due to small parasitic capacitance.
High mobility GaAs layers obtained by open tube sulfur diffusion
Authors: Prince F. C. , Oren M. , Lam M.
Published: July 2002

A new technique to diffuse sulfur in GaAs has been demonstrated. The diffusion is performed on a 2-in. liquid encapsulated Czochralski GaAs wafer in an open tube furnace under N2 flow. A graphite assembly is used to keep the diffusion source and the wafer in close proximity. Diffusion at 850 °C for 30 min gave a sheet carrier concentration of 8.2×1012 cm−2, average mobility of 4200 cm2/V s, and sheet resistance of 180 Ω/⧠. Sheet resistance uniformity is about ±5%. Transconductances as high as 200 mS/mm have been measured on metal-semiconductor field-effect transistors with 2 μm gate length, fabricated on layers diffused by this technique.
Cesium coverage on molybdenum due to cesium ion bombardment
Authors: Tompa G. S. , Carr W. E. , Seidl M.
Published: July 2002

Cesium coverage due to Cs+ bombardment of a polycrystalline molybdenum surface was investigated in the incident energy range below 500 eV. When the surface is exposed to a Cs+ beam the work function decreases until steady state is reached with a total dose of less than ≊1×1016 ions/cm2. The steady state work function reaches a minimum at an incident energy of ≊100 eV and slowly increases with bombarding energy. Cesium coverage of a target is proportional to the ratio (1−β)/γ, where β is the reflection coefficient and γ is the sputter yield. This ratio is large for molybdenum because of its low mass and high binding energy. Implications of these results for H− surface conversion sources are discussed.
Continuous wave and Q-switched infrared erbium laser
Authors: Pollack S. A. , Chang D. B. , Moise N. L.
Published: July 2002

Upconversion pumping has been demonstrated both experimentally and theoretically to be important in the 2.8-μm 4I11/2–4I13/2 lasing transition in a CaF2 (Er3+) system. A minimum pump threshold of only 2.8 J with a 1-ms Xe lamp pulse has been achieved in CaF2 rods containing 5 mol % of Er3+ ions. A simple theory has been developed to show that upconversion pumping makes possible cw lasing between the 4I11/2 and 4I13/2 states even when the lifetime of the terminal 4I13/2 state is much longer than that of the upper 4I11/2 state. Semi-cw lasing has been experimentally demonstrated by pumping with six ganged photographic flash bulbs fired in sequence, with each bulb having a duration of 15–20 ms. Lasing at 2.8 μm lasted for 80 ms, well beyond 10 and 20 ms lifetimes of the 4I11/2 and 4I13/2 states. The 2.8-μm CaF2 (Er3+) laser has also been Q switched, using a 100-nm thin graphite foil as a shutter.
Wavelength shift of the ruby luminescence R lines under shock compression
Authors: Horn P. D. , Gupta Y. M.
Published: July 2002

A method has been developed to measure the time-resolved, stress-induced wavelength shift of ruby luminescence under shock loading. Results of experiments at 40 and 99 kbar stresses are presented and compared with high pressure hydrostatic data. A brief discussion of the necessary improvements to obtain high resolution shock data to permit quantitative analysis is presented.
Novel oxidation process in Ge+-implanted Si and its effect on oxidation kinetics
Authors: Holland O. W. , White C. W. , Fathy D.
Published: July 2002

Thermal oxidation of Si is shown to be substantially affected by the implantation of Ge+ ions. A unique morphology develops during steam oxidation due to the rejection of Ge from the oxide at the growth interface. The Ge pile-up leads to the formation of a distinct layer of almost pure Ge between the oxide and the underlying Si. Oxidation rates are enhanced due to the presence of this film which is shown to increase the interfacial reaction rate. This increase is attributed to a decrease in the binding energy of Si atoms at the interface as a result of alloying with the Ge film. A model is proposed to account for the enhanced oxidation kinetics and is shown to be in good agreement with experimental data.
Point defect/dopant diffusion considerations following preamorphization of silicon via Si+ and Ge+ implantation
Authors: Ajmera A. C. , Rozgonyi G. A. , Fair R. B.
Published: July 2002

A comparison has been made between two shallow preamorphization techniques using Si+ and Ge+ implantation, followed by B+ implantation and rapid thermal annealing (RTA). The subsequent impact on boron diffusion profiles and extended defects have been examined experimentally with secondary ion mass spectroscopy and cross-section transmission electron microscopy, and theoretically with the predict computer program, in an attempt to generalize the observations. Enhanced or retarded B diffusion during RTA has been correlated with the relative depths of the original amorphous/crystalline interface and the as-implanted B profiles, with ion type used for preamorphization, and with the initial type and relative location of the radiation-induced point defects. In general, Si+ self-implant samples showed less B profile broadening than Ge+ implant samples following RTA at 1050 °C for 10 s. The conditions necessary for complete annihilation of end-of-range interstitial loops for Si+ self-amorphization are specified.
Disordering of the ordered structure in metalorganic chemical vapor deposition grown Ga0.5In0.5P on (001) GaAs substrates by zinc diffusion
Authors: Dabkowski F. P. , Gavrilovic P. , Meehan K. , Stutius W. , Williams J. E. , Shahid M. A. , Mahajan S.
Published: July 2002

Transmission electron microscopy is used to study sublattice atomic ordering in as-grown and Zn-diffused epitaxial layers of Ga0.5In0.5P that are grown lattice matched to GaAs by low-pressure metalorganic chemical vapor deposition. The as-grown Ga0.5In0.5P layers exhibit an ordered trigonal structure with In-Ga ordering occurring on only two sets of {111} planes. After a Zn diffusion is performed at 650 °C, the ordered structure is no longer observed in selected area diffraction patterns. Simultaneously, the room-temperature photoluminescence peak shifts by ≊90 meV to higher energy, as compared to the undiffused samples. These data provide direct experimental evidence that Ga0.5In0.5P with an ordered distribution of Ga and In atoms on the column III sublattice can be converted to a random alloy by Zn diffusion.
Neuronal activity-dependent membrane traffic at the neuromuscular junction
Authors: Miana-Mena Francisco Javier , Roux Sylvie , Benichou Jean-Claude , Osta Rosario , Brûlet Philippe
Published: July 2002

During development and also in adulthood, synaptic connections are modulated by neuronal activity. To follow such modifications
in vivo
, new genetic tools are designed. The nontoxic C-terminal fragment of tetanus toxin (TTC) fused to a reporter gene such as
LacZ
retains the retrograde and transsynaptic transport abilities of the holotoxin itself. In this work, the hybrid protein is injected intramuscularly to analyze
in vivo
the mechanisms of intracellular and transneuronal traffics at the neuromuscular junction (NMJ). Traffic on both sides of the synapse are strongly dependent on presynaptic neural cell activity. In muscle, a directional membrane traffic concentrates β-galactosidase-TTC hybrid protein into the NMJ postsynaptic side. In neurons, the probe is sorted across the cell to dendrites and subsequently to an interconnected neuron. Such fusion protein, sensitive to presynaptic neuronal activity, would be extremely useful to analyze morphological changes and plasticity at the NMJ.
A basolateral sorting motif in the MICA cytoplasmic tail
Authors: Suemizu Hiroshi , Radosavljevic Mirjana , Kimura Minoru , Sadahiro Sotaro , Yoshimura Shinichi , Bahram Seiamak , Inoko Hidetoshi
Published: July 2002

The MHC class I chain-related MICA molecule is a stress-induced, highly polymorphic, epithelia-specific, membrane-bound glycoprotein interacting with the activating NK cell receptor NKG2D and/or gut-enriched Vδ1-bearing γδ T cells. We have previously reported the presence of a MICA transmembrane-encoded short-tandem repeat harboring a peculiar allele, A5.1, characterized by a frame shift mutation leading to a premature intradomain stop codon, thus denying the molecule of its 42-aa cytoplasmic tail. Given that this is the most common population-wide MICA allele found, we set out to analyze the functional consequences of cytoplasmic tail deletion. Here, we show native expression of MICA at the basolateral surface of human intestinal epithelium, the site of putative interaction with intraepithelial T and NK lymphocytes. We then demonstrate, in polarized epithelial cells, that although the full-length MICA protein is sorted to the basolateral membrane, the cytoplasmic tail-deleted construct as well as the naturally occurring A5.1 allele are aberrantly transported to the apical surface. Site-directed mutagenesis identified the cytoplasmic tail-encoded leucine-valine dihydrophobic tandem as the basolateral sorting signal. Hence, the physiological location of MICA within epithelial cells is governed by its cytoplasmic tail, implying impairment in A5.1 homozygous individuals, perhaps relevant to the immunological surveillance exerted by NK and T lymphocytes on epithelial malignancies.
Construction of a rationally designed human cytomegalovirus variant encoding a temperature-sensitive immediate-early 2 protein
Authors: Heider Julie A. , Bresnahan Wade A. , Shenk Thomas E.
Published: July 2002

We generated a set of cysteine-to-glycine mutations and screened them to identify a temperature-sensitive allele of the human cytomegalovirus UL122 gene, which encodes the immediate-early 2 transcriptional activating protein. The mutant allele contains a single base pair substitution at amino acid 510. In transcription activation assays, the mutant protein activated the simian virus 40 early and human cytomegalovirus UL112 promoters at 32.5°C but not at 39.5°C. We constructed a mutant virus, BTN
ts
UL122, in which the wild-type UL122 locus is substituted with the mutant allele. The mutant produced progeny at 32.5°C but not at 39.5°C. Although the mutant virus accumulated immediate-early transcripts and proteins at the nonpermissive temperature, it did not produce any early (UL44 and UL54) and late (UL82) transcripts and it did not replicate its DNA. The mutant's defect at the nonpermissive temperature results, at least in part, from the inability of the temperature-sensitive immediate-early 2 protein to activate early viral promoters, whose products are required for DNA replication and progression into the late phase of the virus growth cycle.
The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structure
Authors: Dinman Jonathan D. , Richter Sara , Plant Ewan P. , Taylor Ronald C. , Hammell Amy B. , Rana Tariq M.
Published: July 2002

The cis-acting mRNA elements that promote programmed −1 ribosomal frameshifting present a natural target for the rational design of antiretroviral chemotherapies. It has been commonly accepted that the HIV-1 frameshifting signal is special, because its downstream enhancer element consists of a simple mRNA stem loop rather than a more complex secondary structure such as a pseudoknot. Here we present three lines of evidence, bioinformatic, structural, and genetic, showing that the biologically relevant HIV-1 frameshift signal contains a complex RNA structure that likely includes an extended RNA triple-helix region. We suggest that the potential intramolecular triplex structure is essential for viral propagation and viability, and that small molecules targeted to this RNA structure may possess antiretroviral activities.
Assembling filamentous phage occlude pIV channels
Authors: Marciano Denise K. , Russel Marjorie , Simon Sanford M.
Published: July 2002

Filamentous phage f1 is exported from its
Escherichia coli
host without killing the bacterial cell. Phage-encoded protein pIV, which is required for phage assembly and secretion, forms large highly conductive channels in the outer membrane of
E. coli
. It has been proposed that the phage are extruded across the bacterial outer membrane through pIV channels. To test this prediction, we developed an
in vivo
assay by using a mutant pIV that functions in phage export but whose channel opens in the absence of phage extrusion. In
E. coli
lacking its native maltooligosacharride transporter LamB, this pIV variant allowed oligosaccharide transport across the outer membrane. This entry of oligosaccharide was decreased by phage production and still further decreased by production of phage that cannot be released from the cell surface. Thus, exiting phage block the pIV-dependent entry of oligosaccharide, suggesting that phage occupy the lumen of pIV channels. This study provides the first evidence, to our knowledge, for viral exit through a large aqueous channel.
UV-damage-mediated induction of homologous recombination in
Arabidopsis
is dependent on photosynthetically active radiation
Authors: Ries Gerhard , Buchholz Günther , Frohnmeyer Hanns , Hohn Barbara
Published: July 2002

Plants are continuously subjected to UV-B radiation (UV-B; 280–320
nm) as a component of sunlight causing damage to the genome. For
elimination of DNA damage, a set of repair mechanisms, mainly
photoreactivation, excision, and recombination repair, has evolved.
Whereas photoreactivation and excision repair have been intensely
studied during the last few years, recombination repair, its
regulation, and its interrelationship with photoreactivation in
response to UV-B-induced DNA damage is still poorly understood. In this
study, we analyzed somatic homologous recombination in a transgenic
Arabidopsis
line carrying a β-glucuronidase gene as a
recombination marker and in offsprings of crosses of this line with a
photolyase deficient
uvr2–1
mutant. UV-B radiation
stimulated recombination frequencies in a dose-dependent manner
correlating linearly with cyclobutane pyrimidine dimer (CPD) levels.
Genetic deficiency for CPD-specific photoreactivation resulted in a
drastic increase of recombination events, indicating that homologous
recombination might be directly involved in eliminating CPD damage.
UV-B irradiation stimulated recombination mainly in the presence of
photosynthetic active radiation (400–700 nm) irrespective of
photolyase activities. Our results suggest that UV-B-induced
recombination processes may depend on energy supply derived from
photosynthesis.
CrkII signals from epidermal growth factor receptor to Ras.
Authors: Kizaka-Kondoh S , Matsuda M , Okayama H
Published: July 2002

A rat fibroblast mutant defective in oncogenic transformation and signaling from epidermal growth factor receptor to Ras has been isolated. The mutant contains dominant negative-type point mutations in the C-terminal SH3 domain of one crkII gene. Among the adapters tested, the mutant is complemented only by crkII cDNA. Expression of the mutated crkII in parent cells generates the phenotype indistinguishable from the mutant cell. Yet overexpression or reduced expression of Grb2 in the mutant before and after complementation with crkII have little effect on its phenotype. We conclude that adapter molecules are highly specific and that the oncogenic growth signal from epidermal growth factor receptor to Ras is predominantly mediated by CrkII in rat fibroblast.
From symmetry to asymmetry: Phylogenetic patterns of asymmetry variation in animals and their evolutionary significance
Authors: Palmer A. Richard
Published: July 2002

Phylogenetic analyses of asymmetry variation offer a powerful tool
for exploring the interplay between ontogeny and evolution because
(
i
) conspicuous asymmetries exist in many higher metazoans
with widely varying modes of development, (
ii
) patterns of
bilateral variation within species may identify genetically and
environmentally triggered asymmetries, and (
iii
)
asymmetries arising at different times during development may be more
sensitive to internal cytoplasmic inhomogeneities compared to external
environmental stimuli. Using four broadly comparable asymmetry states
(symmetry, antisymmetry, dextral, and sinistral), and two stages at
which asymmetry appears developmentally (larval and postlarval), I
evaluated relations between ontogenetic and phylogenetic patterns of
asymmetry variation. Among 140 inferred phylogenetic transitions
between asymmetry states, recorded from 11 classes in five phyla,
directional asymmetry (dextral or sinistral) evolved directly from
symmetrical ancestors proportionally more frequently among larval
asymmetries. In contrast, antisymmetry, either as an end state or as a
transitional stage preceding directional asymmetry, was confined
primarily to postlarval asymmetries. The ontogenetic origin of
asymmetry thus significantly influences its subsequent evolution.
Furthermore, because antisymmetry typically signals an environmentally
triggered asymmetry, the phylogenetic transition from antisymmetry to
directional asymmetry suggests that many cases of laterally fixed
asymmetries evolved via genetic assimilation.
Retinal glial cell glutamate transporter is coupled to an anionic conductance.
Authors: Eliasof S , Jahr C E
Published: July 2002

Application of L-glutamate to retinal glial (Müller) cells results in an inwardly rectifying current due to the net influx of one positive charge per molecule of glutamate transported into the cell. However, at positive potentials an outward current can be elicited by glutamate. This outward current is eliminated by removal of external chloride ions. Substitution of external chloride with the anions thiocyanate, perchlorate, nitrate, and iodide, which are known to be more permeant at other chloride channels, results in a considerably larger glutamate-elicited outward current at positive potentials. The large outward current in external nitrate has the same ionic dependence, apparent affinity for L-glutamate, and pharmacology as the glutamate transporter previously reported to exist in these cells. Varying the concentration of external nitrate shifts the reversal potential in a manner consistent with a conductance permeable to nitrate. Together, these results suggest that the glutamate transporter in retinal glial cells is associated with an anionic conductance. This anionic conductance may be important for preventing a reduction in the rate of transport due the depolarization that would otherwise occur as a result of electrogenic glutamate uptake.
Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis.
Authors: Crews C M , Lane W S , Schreiber S L
Published: July 2002

The marine natural product didemnin B, currently in clinical trials as an antitumor agent, has several potent biological activities apparently mediated by distinct mechanisms. Our initial investigation of didemnin B resulted in the discovery of its GTP-dependent binding of the translation elongation factor EF1 alpha. This finding is consistent with the protein synthesis inhibitory activity of didemnin B observed at intermediate concentrations. To begin to dissect the mechanisms involved in the cytostatic and immunosuppressive activities of didemnin B, observed at low concentrations, additional didemnin-binding proteins were sought. Here we report the purification of a 36-kDa glycosylated didemnin-binding protein from bovine brain lysate. Cloning of the human cDNA encoding this protein revealed a strong sequence similarity with palmitoyl protein thioesterase (PPT), an enzyme that removes palmitate from H-Ras and the G alpha s subunits of heterotrimeric GTP-binding proteins in vitro. Mutations in PPT have recently been shown to be responsible for infantile neuronal ceroid lipofuscinosis, which is a severe brain disorder characterized by progressive loss of brain function and early death.
Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase
Authors: Patki Varsha , Virbasius Joe , Lane William S. , Toh Ban-Hock , Shpetner Howard S. , Corvera Silvia
Published: July 2002

Phosphatidylinositol 3-kinases (PI 3-kinases) have been implicated in membrane trafficking in the secretory and endocytic pathways of yeast and mammalian cells, but the molecular mechanisms by which these lipid kinases operate are not known. Here we identify a protein of 170 kDa that is rapidly released from cell membranes in response to wortmannin, a potent inhibitor of mammalian PI 3-kinases. The amino acid sequence of peptides from p170 reveal its identity to early endosomal antigen (EEA) 1, an endosomal antigen with homology to several yeast proteins genetically implicated in membrane trafficking. Immunofluorescence analysis of 3T3-L1 adipocytes with antisera against p170/EEA1 reveal a punctate peripheral pattern that becomes diffuse in response to wortmannin.
In vitro
, p170/EEA1 binds specifically to liposomes containing PIns(3)P, suggesting that the effect of wortmannin on cells is due to inhibition of PIns(3)P production. Thus, p170/EEA1 may define a family of proteins that mediate the regulatory effects of 3′-phosphoinositides on membrane trafficking in yeast and mammalian cells.
Electrophysiological studies on rat dorsal root ganglion neurons after peripheral axotomy: Changes in responses to neuropeptides
Authors: Xu Zhi-Qing David , Zhang Xu , Grillner Sten , Hökfelt Tomas
Published: July 2002

The effect of three peptides, galanin, sulfated cholecystokinin octapeptide, and neurotensin (NT), was studied on acutely extirpated rat dorsal root ganglia (DRGs)
in vitro
with intracellular recording techniques. Both normal and peripherally axotomized DRGs were analyzed, and recordings were made from C-type (small) and A-type (large) neurons. Galanin and sulfated cholecystokinin octapeptide, with one exception, had no effect on normal C- and A-type neurons but caused an inward current in both types of neurons after sciatic nerve cut. In normal rats, NT caused an outward current in C-type neurons and an inward current in A-type neurons. After sciatic nerve cut, NT only caused an inward current in both C- and A-type neurons. These results suggest that (
i
) normal DRG neurons express receptors on their soma for some but not all peptides studied, (
ii
) C- and A-type neurons can have different types of receptors, and (
iii
) peripheral nerve injury can change the receptor phenotype of both C- and A-type neurons and may have differential effects on these neuron types.
Aldehyde dehydrogenase class 3 expression: Identification of a cornea-preferred gene promoter in transgenic mice
Authors: Kays W. Todd , Piatigorsky Joram
Published: July 2002

Aldehyde dehydrogenase class 3 (ALDH3) constitutes 20–40% of the total water-soluble proteins in the mammalian cornea. Here, we show by Northern blot analysis that ALDH3 expression in the mouse is at least 500-fold higher in the cornea than in any other tissue examined, with very low levels of expression detected in the stomach, urinary bladder, ocular lens, and lung. Histochemical localization reveals that this exceptional level of expression in the mouse cornea occurs in the anterior epithelial cells and that little ALDH3 is present in the keratocytes or corneal endothelial cells. A 13-kbp mouse ALDH3 promoter fragment containing >12 kbp of the 5′ flanking sequence, the 40-bp untranslated first exon, and 29 bp of intron 1 directed
cat
reporter gene expression to tissues that express the endogenous ALDH3 gene, except that transgene promoter activity was higher in the stomach and bladder than in the cornea. By contrast, when driven by a 4.4-kbp mouse ALDH3 promoter fragment [1,050-bp 5′ flanking region, exon 1, intron 1 (3.4 kbp), and 7 bp of exon 2] expression of the
cat
reporter gene was confined to the corneal epithelial cells, except for very low levels in the liver, effectively reproducing the corneal expression pattern of the endogenous ALDH3 gene. These results indicate that tissue-specific expression of ALDH3 is determined by positive and negative elements in the 5′ flanking region of the gene and suggests putative silencers located in intron 1. We demonstrate regulatory sequences capable of directing cornea-specific gene expression, affording the opportunity for genetic engineering in this transparent tissue.
How the owl resolves auditory coding ambiguity
Authors: Mazer James A.
Published: July 2002

The barn owl (
Tyto alba
) uses interaural time difference (ITD) cues to localize sounds in the horizontal plane. Low-order binaural auditory neurons with sharp frequency tuning act as narrow-band coincidence detectors; such neurons respond equally well to sounds with a particular ITD and its phase equivalents and are said to be phase ambiguous. Higher-order neurons with broad frequency tuning are unambiguously selective for single ITDs in response to broad-band sounds and show little or no response to phase equivalents. Selectivity for single ITDs is thought to arise from the convergence of parallel, narrow-band frequency channels that originate in the cochlea. ITD tuning to variable bandwidth stimuli was measured in higher-order neurons of the owl’s inferior colliculus to examine the rules that govern the relationship between frequency channel convergence and the resolution of phase ambiguity. Ambiguity decreased as stimulus bandwidth increased, reaching a minimum at 2–3 kHz. Two independent mechanisms appear to contribute to the elimination of ambiguity: one suppressive and one facilitative. The integration of information carried by parallel, distributed processing channels is a common theme of sensory processing that spans both modality and species boundaries. The principles underlying the resolution of phase ambiguity and frequency channel convergence in the owl may have implications for other sensory systems, such as electrolocation in electric fish and the computation of binocular disparity in the avian and mammalian visual systems.
A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity
Authors: Lebel Michel , Leder Philip
Published: July 2002

Werner syndrome (WS) is an autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases. The gene responsible for WS encodes a member of the RecQ-like subfamily of DNA helicases. Here we show that its murine homologue maps to murine chromosome 8 in a region syntenic with the human
WRN
gene. We have deleted a segment of this gene and created
Wrn
-deficient embryonic stem (ES) cells and WS mice. While displaying reduced embryonic survival, live-born WS mice otherwise appear normal during their first year of life. Nonetheless, although several DNA repair systems are apparently intact in homozygous WS ES cells, such cells display a higher mutation rate and are significantly more sensitive to topoisomerase inhibitors (especially camptothecin) than are wild-type ES cells. Furthermore, mouse embryo fibroblasts derived from homozygous WS embryos show premature loss of proliferative capacity. At the molecular level, wild-type, but not mutant, WS protein copurifies through a series of centrifugation and chromatography steps with a multiprotein DNA replication complex.
A family of chimeric erythrocyte binding proteins of malaria parasites
Authors: Kappe Stefan H. I. , Noe Amy R. , Fraser Tresa S. , Blair Peter L. , Adams John H.
Published: July 2002

Proteins sequestered within organelles of the apical complex of malaria merozoites are involved in erythrocyte invasion, but few of these proteins and their interaction with the host erythrocyte have been characterized. In this report we describe MAEBL, a family of erythrocyte binding proteins identified in the rodent malaria parasites
Plasmodium yoelii yoelii
and
Plasmodium berghei
. MAEBL has a chimeric character, uniting domains from two distinct apical organelle protein families within one protein. MAEBL has a molecular structure homologous to the Duffy binding-like family of erythrocyte binding proteins located in the micronemes of merozoites. However, the amino cysteine-rich domain of MAEBL has no similarity to the consensus Duffy binding-like amino cysteine-rich ligand domain, but instead is similar to the 44-kDa ectodomain fragment of the apical membrane antigen 1 (AMA-1) rhoptry protein family. MAEBL has a tandem duplication of this AMA-1-like domain, and both of these cysteine-rich domains bound erythrocytes when expressed
in vitro
. Differential transcription and splicing of the
maebl
locus occurred in the YM clone of
P. yoelii yoelii
. The apical distribution of MAEBL suggested localization within the rhoptry organelles of the apical complex. We propose that MAEBL is a member of a highly conserved family of erythrocyte binding proteins of
Plasmodium
involved in host cell invasion.
Molecular cloning, characterization, and promoter analysis of the human 25-hydroxyvitamin D3-1α-hydroxylase gene
Authors: Kong Xiang F. , Zhu Xue H. , Pei Yan L. , Jackson David M. , Holick Michael F.
Published: July 2002

The human 25-hydroxyvitamin D3-1α-hydroxylase (1α-OHase) gene has been cloned. It contained nine exons and eight introns spanning ≈6.5 kb and a 1.4-kb 5′-flanking region. The 5′-flanking region contains consensus or highly conserved sequences for TATA, Pu, and CCAAT boxes, four cAMP response elements, two activator protein-1 (AP-1) response elements, two AP-2 response elements, three specific protein-1 (Sp1) response elements, and four NF-κB binding sites, but no vitamin D response element. By using luciferase reporter gene constructs of truncated forms of the 1α-OHase promoter transfected into a modified pig kidney cell line, AOK-B50, we identified regulatory regions of the 1.4-kb 1α-OHase promoter for parathyroid hormone 1–34 [PTH(1–34)], forskolin, and 1,25-hydroxyvitamin D3[1,25(OH)2D3]. The 1.4-kb 1α-OHase promoter (AN1) modestly (1.7-fold) induced luciferase activity, whereas 1,100- (AN2), 827- (AN3), 672- (AN4), 463-(AN5), and 363-bp (AN6)-truncated promoters greatly stimulated luciferase activity by 494-fold, 18.4-fold, 55.3-fold, 643-fold, and 56.4-fold, respectively. PTH(1–34) and forskolin stimulated the activity of all constructs to varying degrees with significantly greater responsiveness for both compounds on AN2 and AN5. 1,25(OH)2D3suppressed PTH(1–34)-induced activity on AN2 and AN5 constructs by 58% and 52%, respectively, but had no effect on the other constructs. These studies characterize the regulatory regions of the human 1α-OHase gene and provide insight into the physiologic basis for regulation of the expression of this gene by PTH and 1,25(OH)2D3.
Stability of the mitochondrial genome requires an amino-terminal domain of yeast mitochondrial RNA polymerase
Authors: Wang Yuanhong , Shadel Gerald S.
Published: July 2002

Mitochondrial RNA (mtRNA) polymerases are related to bacteriophage RNA polymerases, but contain a unique amino-terminal extension of unknown origin and function. In addition to harboring mitochondrial targeting information, we show here that the amino-terminal extension of yeast mtRNA polymerase is required for a mtDNA maintenance function that is separable from the known RNA polymerization activity of the enzyme. Deletion of 185 N-terminal amino acids from the enzyme results in a temperature-sensitive mitochondrial petite phenotype, characterized by increased instability and eventual loss of the mitochondrial genome. Mitochondrial transcription initiation
in vivo
is largely unaffected by this mutation and expression of just the amino-terminal portion of the protein in trans partially suppresses the mitochondrial defect, indicating that the amino-terminal extension of the enzyme harbors an independent functional domain that is required for mtDNA replication and/or stability. These results suggest that amino-terminal extensions present in mtRNA polymerases comprise functional domains that couple additional activities to the transcription process in mitochondria.
Synaptic depression creates a switch that controls the frequency of an oscillatory circuit
Authors: Nadim Farzan , Manor Yair , Kopell Nancy , Marder Eve
Published: July 2002

Synaptic depression is a form of short-term plasticity exhibited by many synapses. Nonetheless, the functional significance of synaptic depression in oscillatory networks is not well understood. We show that, in a recurrent inhibitory network that includes an intrinsic oscillator, synaptic depression can give rise to two distinct modes of network operation. When the maximal conductance of the depressing synapse is small, the oscillation period is determined by the oscillator component. Increasing the maximal conductance beyond a threshold value activates a positive-feedback mechanism that greatly enhances the synaptic strength. In this mode, the oscillation period is determined by the strength and dynamics of the depressing synapse. Because of the regenerative nature of the feedback mechanism, the circuit can be switched from one mode of operation to another by a very small change in the maximal conductance of the depressing synapse. Our model was inspired by experimental work on the pyloric network of the lobster. The pyloric network produces a simple motor rhythm generated by a pacemaker neuron that receives feedback inhibition from a depressing synapse. In some preparations, elimination of the synapse had no effect on the period of the rhythm, whereas in other preparations, there was a significant decrease in the period. We propose that the pyloric network can operate in either of the two modes suggested by the model, depending on the maximal conductance of the depressing synapse.
The essential protein encoded by the U
L
31 gene of herpes simplex virus 1 depends for its stability on the presence of U
L
34 protein
Authors: Ye Guo-Jie , Roizman Bernard
Published: July 2002

To pursue an earlier observation that the protein encoded by
the U
L
34 gene binds to intermediate chain of dynein, we
constructed a series of mutants from which sequences encoding the
entire protein (ΔU
L
34) or amino-terminal
[U
L
34Δ(3–119)] or carboxyl-terminal
[U
L
34Δ(245–275)] domains were deleted. The mutant
lacking the sequence encoding the carboxyl-terminal domain grew in all
cell lines tested. The two other mutants replicated only in cell
type-dependent manner and poorly. Rescue of ΔU
L
34 mutant
with a fragment that does not encompass the U
L
31 ORF
restored wild-type phenotype. U
L
34 protein interacts
physically with U
L
31, and the U
L
31 deletion
mutant appears to have a phenotype similar to that of U
L
34
deletion mutant. Experiments designed to determine whether the
phenotypes of the deletion mutants have a common base revealed that
cells infected with the ΔU
L
34 mutant accumulate
U
L
31 RNA but not the corresponding protein. The
U
L
31 protein accumulated, however, to near wild-type
virus-infected cell levels in cells infected with ΔU
L
34
mutant and treated with the MG132 proteosomal inhibitor at 6
h after infection. This is evidence that the stability of an
essential viral protein requires the presence of another protein. The
observation raises the bar for identification of gene function on the
basis of analyses of the phenotype of mutants in which the gene has
been deleted or rendered inoperative.
Caspase Requirement for Neuronal Apoptosis and Neurodegeneration
Authors: Nicotera Pierluigi
Published: July 2002

The execution of the apoptotic programme involves a relatively few pathways that converge on activation of the caspase family of proteases. However, increasing evidence indicates that apoptoticlike features can be found also when cells are treated with inhibitors of caspases. This has posed questions as to whether death with apoptotic features can still occur in a caspase‐independent way, and whether caspase inhibitors may then be used to prevent excess apoptosis in disease. Metabolic defects, loss of neuronal connectivity and cell loss characterise several neurodegenerative diseases. Targeting excessive cell demise may be one therapeutic strategy. However, loss of connectivity and neurite regression may not be part of the apoptotic programme, and degenerating neurons might use multiple execution pathways. In addition, metabolic defects leading to ATP depletion can preclude caspase activation and consequently switch execution of cell death towards necrosis. The possibility of inhibiting apoptosis as strategy to treat neurodegenerative disease is discussed in this review.
The Yeast Gene, MDM20, Is Necessary for Mitochondrial Inheritance and Organization of the Actin Cytoskeleton
Authors: Hermann Greg J. , King Edward J. , Shaw Janet M.
Published: July 2002

In Saccharomyces cerevisiae, the growing bud inherits a portion of the mitochondrial network from the mother cell soon after it emerges. Although this polarized transport of mitochondria is thought to require functions of the cytoskeleton, there are conflicting reports concerning the nature of the cytoskeletal element involved. Here we report the isolation of a yeast mutant, mdm20, in which both mitochondrial inheritance and actin cables (bundles of actin filaments) are disrupted. The MDM20 gene encodes a 93-kD polypeptide with no homology to other characterized proteins. Extra copies of TPM1, a gene encoding the actin filament–binding protein tropomyosin, suppress mitochondrial inheritance defects and partially restore actin cables in mdm20Δ cells. Synthetic lethality is also observed between mdm20 and tpm1 mutant strains. Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant phenotypes in the mdm20 strain to a lesser extent. Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process. MDM20 and TPM1 also exhibit the same pattern of genetic interactions; mutations in MDM20 are synthetically lethal with mutations in BEM2 and MYO2 but not SAC6. Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents. Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton.