bluuebunny/crossref_metadata_2025 huggingface dataset:
High confinement dissipative divertor operation on Alcator C-Mod
Authors: Goetz J. A. , LaBombard B. , Lipschultz B. , Pitcher C. S. , Terry J. L. , Boswell C. , Gangadhara S. , Pappas D. , Weaver J. , Welch B. , Boivin R. L. , Bonoli P. , Fiore C. , Granetz R. , Greenwald M. , Hubbard A. , Hutchinson I. , Irby J. , Marmar E. , Mossessian D. , Porkolab M. , Rice J. , Rowan W. L. , Schilling G. , Snipes J. , Takase Y. , Wolfe S. , Wukitch S.
Published: July 2002

Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] has operated a High-confinement-mode (H-mode) plasma together with a dissipative divertor and low core Zeff. The initially attached plasma is characterized by steady-state enhancement factor, HITER89P [P. N. Yushmanov et al., Nucl. Fusion 30, 1999 (1990)], of 1.9, central Zeff of 1.1, and a radiative fraction of ∼50%. Feedback control of a nitrogen gas puff is used to increase radiative losses in both the core/edge and divertor plasmas in almost equal amounts. Simultaneously, the core plasma maintains HITER89P of 1.6 and Zeff of 1.4 in this nearly 100% radiative state. The power and particle flux to the divertor plates have been reduced to very low levels while the core plasma is relatively unchanged by the dissipative nature of the divertor.
Relativistic second-harmonic generation and conversion in a weakly magnetized plasma
Authors: Rax J. M. , Robiche J. , Kostyukov I.
Published: July 2002

Relativistic second-harmonic generation with ultrahigh intensity laser pulses in a weakly magnetized plasma is analyzed. Both ordinary mode conversion to second-harmonic extraordinary mode and extraordinary mode conversion to second-harmonic extraordinary mode are considered. Extraordinary mode conversion turns out to be more efficient, and a new frequency doubling scheme based on a tapered magnetic wiggler is identified, described, and analyzed. The important issues of phase matching, pump depletion, and relativistic tapering are addressed and solved. Both permanent magnet and laser-driven wigglers are considered. The interaction of multi-terawatt laser pulses with a magnetized plasma appears to provide an efficient scheme to generate short wavelengths.
Global drift wave map test particle simulations
Authors: Kwon J.-M. , Horton W. , Zhu P. , Morrison P. J. , Park H.-B. , Choi D. I.
Published: July 2002

Global drift wave map equations that allow the integration of particle orbits on long time scales are implemented to describe transport. Ensembles of test particles are tracked to simulate the low-confinement mode/reversed shear/enhanced reversed shear plasmas in the Tokamak Fusion Test Reactor (TFTR) tokamak and the Optimized Shear plasma in the Joint European Torus (JET) tokamak. The simulations incorporate a radial electric field, Ēr, obtained from a neoclassical calculation [Zhu et al., Phys. Plasmas 6, 2503 (1999)] and a model for drift wave fluctuations that takes into account change in the mode structure due to Ēr [Taylor et al., Plasma Phys. Controlled Fusion 38, 1999 (1996)]. Steady state particle density profiles along with two different measures of transport, the diffusion coefficient based on a running time average of the particle displacement and that calculated from the mean exit time, are obtained. For either weak or reversed magnetic shear and highly sheared Ēr, particle transport barriers are observed to be established. In the presence of such a transport barrier, it is shown that there is, in general, a difference between the two measures of transport. The difference is explained by a simple model of the transport barrier.
Regularized magnetic islands. II. The role of polarization current
Authors: Mikhailovskii A. B. , Pustovitov V. D. , Smolyakov A. I. , Tsypin V. S.
Published: July 2002

The role of polarization current in the problem of rotating magnetic islands in the absence of drift effects is discussed for the case of nonregularized and regularized velocity profiles governed by the perpendicular viscosity. The polarization current is calculated taking into account the finite ion Larmor radius effects. It is shown that, in correspondence with the general rule by Waelbroeck and Fitzpatrick [Phys. Rev. Lett. 78, 1703 (1997)], this current is destabilizing. The destabilizing contribution of the polarization current into the generalized Rutherford equation for the magnetic island width does not depend on whether the profile function is regularized or not. It is shown that the Larmor corrections to the current consist of the sum of two oppositely directed currents and do not contribute into the generalized Rutherford equation.
Off-midplane launch of electron Bernstein waves for current drive in overdense plasmas
Authors: Forest C. B. , Chattopadhyay P. K. , Harvey R. W. , Smirnov A. P.
Published: July 2002

Numerical modeling shows that localized, efficient current drive is possible in overdense toroidal plasmas (such as reversed field pinches and spherical tokamaks) using perpendicular launch of electron Bernstein waves. The wave directionality required for driving current can be obtained by launching the waves above or below the midplane of the torus and is a geometric effect related to the poloidal magnetic field. Wave absorption is strong, a result of the electrostatic nature of the waves, giving efficient suprathermal tail formation and current drive.
Numerical simulations of toroidal Alfvén instabilities excited by trapped energetic ions
Authors: Zheng L.-J. , Chen Liu , Santoro R. A.
Published: July 2002

Extensive magnetohydrodynamic–gyrokinetic hybrid simulations have been carried out to study the excitations of Alfvén instabilities by trapped energetic ions in tokamak plasmas. Depending on the parameters, the most unstable mode can be either the toroidal Alfvén eigenmode (TAE) or the energetic-particle mode (EPM). In both cases, the dominant instability driving mechanism is the resonance with the trapped-particle magnetic precessional drifts. The mode frequencies of the most unstable modes, meanwhile, tend to be near the toroidal frequency gap in order to minimize the continuum damping. It is also demonstrated that the instabilities can be quenched by reversing the magnetic precessional drifts via either negative magnetic shear or locating the magnetic turning points in the inner (strong B) side of the torus.
Optically pumped NO (A 2Σ+→X 2π) ultraviolet laser
Authors: Burrows Michael D. , Baughcum Steven L. , Oldenborg Richard C.
Published: July 2002

Lasing action on the (0,1) and (0,2) γ bands of NO at 237 and 248 nm, respectively, has been obtained by longitudinal pumping of 0.5 Torr of NO on the (0,0) γ-band transition at 227 nm. Typical output pulse energies were 13 μJ at an intrinsic energy conversion efficiency of approximately 15%.
Noncollinear coplanar magneto-optic interaction of guided optical wave and magnetostatic surface waves in yttrium iron garnet-gadolinium gallium garnet waveguides
Authors: Tsai C. S. , Young D. , Chen W. , Adkins L. , Lee C. C. , Glass H.
Published: July 2002

Wideband noncollinear coplanar guided-wave magneto-optic diffraction and mode conversion by magnetostatic surface waves at multigigahertz (3–7 GHz) carrier frequencies in yttrium iron garnet-gadolinium gallium garnet waveguides have been observed and measured in detail for the first time. Interaction configuration, physical mechanisms, summary of a theoretical treatment, and some experimental results obtained at 1.152 μm optical wavelength are presented. This noncollinear coplanar magneto-optic interaction configuration should result in a number of integrated optic devices for wideband communications and signal processing applications at electronically tunable microwave carrier frequencies. The potential advantages of the resulting magneto-optic devices over the existing acousto-optic devices are also discussed.
Calibration curve for infrared spectrophotometry of nitrogen in silicon
Authors: Itoh Yoshiko , Nozaki Tadashi , Masui Tsumoru , Abe Takao
Published: July 2002

A calibration curve for infrared absorptiometry of nitrogen in silicon at 963 cm−1 was obtained by the use of charged particle activation analysis with the 14N(p, α) 11C reaction. For as-grown floating zone (FZ) silicon, it is expressed as [nitrogen concentration at. cm−3)] =(1.83±0.24)×1017 (absorption coefficient). For heat-treated FZ silicon and Czochralski (CZ) silicon, this relation was found to give underestimated nitrogen concentration suggesting the existence of infrared insensitive nitrogen.
Minimizing dc drift in LiNbO3 waveguide devices
Authors: Gee C. M. , Thurmond G. D. , Blauvelt H. , Yen H. W.
Published: July 2002

Improved stability against electrical dc bias drift has been demonstrated in LiNbO3 electro-optic modulators by replacing the commonly used SiO2 buffer layer with indium tin oxide (ITO), a transparent conductor. The long term drift of the modulators having an ITO buffer layer with a sheet resistivity of ∼20 Ω/⧠ is less than 0.3% in 8 h. The mechanism of the dc drift phenomenon is discussed using an electrical equivalent circuit model of the modulator.
Channeling studies of InGaAs ternary alloys and InGaAs/InP superlattices grown by metalorganic chemical vapor deposition
Authors: Haga T. , Kimura T. , Abe Y. , Fukui T. , Saito H.
Published: July 2002

The first experimental results of InGaAs ternary alloys and InGaAs/InP superlattices investigated by ion channeling methods are reported. All samples are grown by metalorganic chemical vapor deposition. It is emphasized that the small atomic displacements from virtual crystal points in the ternary alloys have a very important role for dechanneling. Furthermore, it is revealed that the dechanneling fractions along the 〈100〉 directions in the superlattices which have small lattice mismatches (0.1∼0.3%) are not explained by the model of a strained-layer superlattice, even if the atomic displacements in the ternary alloy layers are taken into account. Main origins of this discrepancy are discussed.
Infrared spectroscopy of interfaces in amorphous hydrogenated silicon/silicon nitride superlattices
Authors: Abeles B. , Yang L. , Persans P. D. , Stasiewski H. S. , Lanford W.
Published: July 2002

Infrared and atomic composition measurements of a-Si:H/a-SiNx:H superlattices as a function of repeat distance show ∼1×1015 cm−2 extra hydrogen bonded to Si at the interface formed when a-Si:H is deposited on a-SiNx:H. The H distribution peaks in the first monolayer and decays in the a-Si:H layer over a distance of ∼19 Å. The hydrogen relieves the large lattice mismatch between the two layers and pacifies defects.
Optical mapping of residual stress in Czochralski grown GaAs
Authors: Dobrilla P. , Blakemore J. S.
Published: July 2002

Despite several detailed theoretical analyses of the stress distribution expected for Czochralski grown GaAs crystals, experimental verification of these calculations has hitherto relied on dislocation density measurements. The present work shows that weak photoelastic patterns are resolvable in the near-infrared transmittance (typically near 1.4 μm) of semi-insulating GaAs wafers. Mapping of these patterns reveals the contours of constant shear stress, with results generally supporting the calculated models for the stress distribution.
Stress relaxation technique for thermally grown SiO2
Authors: Landsberger L. M. , Tiller W. A.
Published: July 2002

A corona discharge technique has been utilized at 800 °C to fully relax thermal oxides grown on Si wafers. In an experiment involving two oxidation steps, the corona-relaxed oxides are shown to be equivalent to ∼1200 °C thermally grown or thermally relaxed oxides, both with respect to index of refraction and oxygen diffusion coefficient. The activation energy for oxygen diffusion through a completely relaxed thermal oxide is found to be 0.8 eV.
Wavelength control of iron/nickel composition in laser induced chemical vapor deposited films
Authors: Armstrong J. V. , Burk A. A. , Coey J. M. D. , Moorjani K.
Published: July 2002

It is shown that the composition of metallic deposits obtained by photodecomposition of a mixture of ferrocene and nickelocene vapor can be varied by selecting the laser wavelength to match features in the absorption spectra. Iron/nickel ratios of 92:8 and 65:35 are obtained by using 193 nm and 337 nm laser lines, respectively.
Energy-band discontinuities in a heterojunction of amorphous hydrogenated Si and crystalline Si measured by internal photoemission
Authors: Mimura Hidenori , Hatanaka Yoshinori
Published: July 2002

Energy-band discontinuities were measured for hydrogenated amorphous silicon and crystalline silicon heterojunctions by internal photoemission. The measurement was performed both for the conduction-band side and for the valence-band side, and the conduction-band discontinuity and the valence-band discontinuity were estimated to be 0.09 and 0.71 eV, respectively. This result indicates that the band discontinuity mainly exists at the valence-band side.
Mechanism of hydrocarbon formation upon interaction of energetic hydrogen ions with graphite
Authors: Roth J. , Bohdansky J.
Published: July 2002

The current model for hydrocarbon formation upon the interaction of energetic hydrogen ions with graphite assumes a reaction of adsorbed hydrogen with carbon surface atoms requiring a temperature of 800–900 K. This model is strongly questioned by results of hydrocarbon formation from a layered 13C/12C sample and by desorption measurements after room-temperature implantation. The formation of 13CD4 and 12CD4 is monitored during deuterium bombardment of a pyrolytic graphite sample covered with a layer of 200 Å of 13C. Only for ion energies corresponding to ranges smaller than 200 Å 13CD4 dominates, while at higher energies only 12CD4 is found. The methane is thus formed at the end of ion range rather than in a surface reaction of back-diffusing ions. Desorption experiments using a slow temperature range after room-temperature implantation show the release of CD4 prior to D2, thus indicating a diffusion-limited release of CD4 already formed during the implantation.
Noninteger InAs monolayer well InAs/GaAs single quantum well structures grown by metalorganic chemical vapor deposition
Authors: Taira K. , Kawai H. , Hase I. , Kaneko K. , Watanabe N.
Published: July 2002

InAs/GaAs single quantum well structures have been grown by metalorganic chemical vapor deposition. The grown wells are 1.03, 1.3, and 1.7 InAs monolayers thick. The 4 K photoluminescence spectra exhibit strong and narrow peaks, their energy decreasing smoothly with increasing well thickness. The noninteger value is interpreted on the model that the interface is macroscopically flat but has valleys and hills with their lateral extent smaller than excitons. The effective interface position is determined by their relative lateral extent.
Relativistic focusing and beat wave phase velocity control in the plasma beat wave accelerator
Authors: Esarey E. , Ting A. , Sprangle P.
Published: July 2002

Relativistic focusing allows two collinear short pulse radiation beams, provided they are of sufficiently high power, to propagate through a plasma without diffracting. By further accounting for finite radial beam geometry, it is possible for the phase velocity of the radiation beat (ponderomotive) wave to equal to the speed of light. This removes one of the limiting factors, phase detuning between the accelerated electrons and the beat wave, in determining the maximum energy gain in the plasma beat wave accelerator.
A role for biliverdin IXα in dorsal axis development of
Xenopus laevis
embryos
Authors: Falchuk Kenneth H. , Contin Jennifer M. , Dziedzic T. Scott , Feng Zhongling , French Thayer C. , Heffron Gregory J. , Montorzi Marcelo
Published: July 2002

The determinants of
Xenopus
laevis
embryos that act before their first cell division are mandatory for the
formation of mRNas required to establish the dorsal axis. Although
their chemical identities are unknown, a number of their properties
have long been recognized. One of the determinants is present in the
cytoplasm and is sensitive to UV light. Thus, exposing stage 1 embryos
to either standard 254-nm or, as shown here, to 366-nm UV light
during the 0.3–0.4 time fraction of their first cycle inactivates the
cytoplasmic determinant. As a consequence, both types of irradiated
embryos fail to express dorsal markers, e.g., goosecoid and chordin,
without affecting formation of ventral markers, e.g., Vent-1. The
developmental outcome is dorsal axis-deficient morphology. We report
here that biliverdin IXα, a normal constituent of cytoplasmic yolk
platelets, is photo-transformed by irradiation with either 254- or
366-nm UV light and that the transformation triggers the dorsal axis
deficiency. When the 254- or 366-nm UV-irradiated embryos, fated to
dorsal axis deficiency, are incubated solely with μM amounts of
biliverdin, they recover and form the axis. In contrast, incubation
with either
in vitro
photo-transformed biliverdin or
biliverdin IXα dimethyl ester does not induce recovery. The results
define an approach to produce dorsal axis-deficient embryos by
photo-transforming its biliverdin by irradiation with 366-nm UV light
and identify an unsuspected role for biliverdin IXα in
X.
laevis
embryogenesis.
The xeroderma pigmentosum group C gene leads to selective repair of cyclobutane pyrimidine dimers rather than 6-4 photoproducts
Authors: Emmert Steffen , Kobayashi Nobuhiko , Khan Sikandar G. , Kraemer Kenneth H.
Published: July 2002

We investigated the contribution of the xeroderma pigmentosum group C (XPC) gene to DNA repair. We stably transfected XPC cells (XP4PA-SV-EB) with XPC cDNA and selected a partially corrected (XP4PA-SE1) and a fully corrected (XP4PA-SE2) clone. Cell survival after UVC (254 nm) exposure was low for XP4PA-SV-EB, intermediate for XP4PA-SE1, and normal for XP4PA-SE2 cells. XP4PA-SV-EB cells had undetectable XPC mRNA and protein levels. XP4PA-SE1 cells had 130% of normal mRNA but 25% of normal protein levels, whereas XP4PA-SE2 cells had an 18-fold mRNA overexpression and normal XPC protein levels compared with normal cells. We measured cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) by using specific mAbs and the ELISA technique. XP4PA-SV-EB cells had no detectable removal of CPD or 6-4PP from their global genome by 24 h after 30 J/m
2
UVC exposure. The partially corrected XP4PA-SE1 cells had normal repair of CPD but minimal repair of 6-4PP by 24 h, whereas the fully corrected XP4PA-SE2 cells regained normal CPD and 6-4PP repair capacities. We also exposed pRSVcat plasmid to UVC (to induce CPD and 6-4PP), to UVC + photolyase (to leave only 6-4PP on the plasmid), or to UVB + acetophenone (to induce only CPD). Host cell reactivation of UVB + acetophenone-, but not of UVC + photolyase-treated plasmids was normal in XP4PA-SE1 cells. Thus, increasing XPC gene expression leads to selective repair of CPD in the global genome. Undetectable XPC protein is associated with no repair of CPD or 6-4PP, detectable but subnormal XPC protein levels reconstitute CPD but not 6-4PP repair, and normal XPC protein levels fully reconstitute both CPD and 6-4PP repair.
Insulin promotes rapid delivery of
N
-methyl-
d
- aspartate receptors to the cell surface by exocytosis
Authors: Skeberdis Vytenis A. , Lan Jian-yu , Zheng Xin , Zukin R. Suzanne , Bennett Michael V. L.
Published: July 2002

Insulin potentiates
N
-methyl-
d
-aspartate
receptors (NMDARs) in neurons and
Xenopus
oocytes
expressing recombinant NMDARs. The present study shows that insulin
induced (
i
) an increase in channel number times open
probability (
nP
o
) in outside-out patches
excised from
Xenopus
oocytes, with no change in mean
open time, unitary conductance, or reversal potential, indicating an
increase in
n
and/or
P
o
;
(
ii
) an increase in charge transfer during block of
NMDA-elicited currents by the open channel blocker MK-801, indicating
increased number of functional NMDARs in the cell membrane with no
change in
P
o
; and (
iii
)
increased NR1 surface expression, as indicated by Western blot analysis
of surface proteins. Botulinum neurotoxin A greatly reduced insulin
potentiation, indicating that insertion of new receptors occurs via
SNARE-dependent exocytosis. Thus, insulin potentiation occurs via
delivery of new channels to the plasma membrane. NMDARs assembled from
mutant subunits lacking all known sites of tyrosine and
serine/threonine phosphorylation in their carboxyl-terminal tails
exhibited robust insulin potentiation, suggesting that insulin
potentiation does not require direct phosphorylation of NMDAR subunits.
Because insulin and insulin receptors are localized to glutamatergic
synapses in the hippocampus, insulin-regulated trafficking of NMDARs
may play a role in synaptic transmission and plasticity, including
long-term potentiation.
Free energy reconstruction from nonequilibrium single-molecule pulling experiments
Authors: Hummer Gerhard , Szabo Attila
Published: July 2002

Laser tweezers and atomic force microscopes are increasingly used
to probe the interactions and mechanical properties of individual
molecules. Unfortunately, using such time-dependent perturbations to
force rare molecular events also drives the system away from
equilibrium. Nevertheless, we show how equilibrium free energy profiles
can be extracted rigorously from repeated nonequilibrium force
measurements on the basis of an extension of Jarzynski's remarkable
identity between free energies and the irreversible work.
Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice
Authors: Lee Joo-Yong , Cole Toby B. , Palmiter Richard D. , Suh Sang Won , Koh Jae-Young
Published: July 2002

Endogenous metals may contribute to the accumulation of amyloid plaques in Alzheimer's disease. To specifically examine the role of synaptic zinc in the plaque accumulation, Tg2576 (also called APP2576) transgenic mice (
hAPP
+
) expressing cerebral amyloid plaque pathology were crossed with mice lacking zinc transporter 3 (
ZnT3
−/−
), which is required for zinc transport into synaptic vesicles. With aging, female
hAPP
+
:
ZnT3
+/+
mice manifested higher levels of synaptic zinc, insoluble amyloid β, and plaques than males; these sex differences disappeared in
hAPP
+
:
ZnT3
−/−
mice. Both sexes of
hAPP
+
:
ZnT3
−/−
mice had markedly reduced plaque load and less insoluble amyloid β compared with
hAPP
+
:
ZnT3
+/+
mice. Hence, of endogenous metals, synaptic zinc contributes predominantly to amyloid deposition in
hAPP
+
mice.
CD8+T cells control the TH phenotype of MBP-reactive CD4+T cells in EAE mice
Authors: Jiang Hong , Braunstein Ned S. , Yu Bin , Winchester Robert , Chess Leonard
Published: July 2002

Trimolecular interactions between the T cell antigen receptor and MHC/peptide complexes, together with costimulatory molecules and cytokines, control the initial activation of naïve T cells and determine whether the helper precursor cell differentiates into either T helper (TH)1 or TH2 effector cells. We now present evidence that regulatory CD8+T cells provide another level of control of TH phenotype during further evolution of immune responses. These regulatory CD8+T cells are induced by antigen-triggered CD4+TH1 cells during T cell vaccination and,in vitro, distinguish mature TH1 from TH2 cells in a T cell antigen receptor Vβ-specific and Qa-1-restricted manner.In vivo, protection from experimental autoimmune encephalomyelitis (EAE) induced by T cell vaccination depends on CD8+T cells, and myelin basic protein-reactive TH1 Vβ8+clones, but not TH2 Vβ8+clones, used as vaccine T cells, protect animals from subsequent induction of EAE. Moreover,in vivodepletion of CD8+T cells during the first episode of EAE results in skewing of the TH phenotype toward TH1 upon secondary myelin basic protein stimulation. These data provide evidence that CD8+T cells control autoimmune responses, in part, by regulating the TH phenotype of self-reactive CD4+T cells.
Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate
Authors: Wang Samuel S.-H. , Khiroug Leonard , Augustine George J.
Published: July 2002

Localized, chemical two-photon photolysis of caged glutamate was used to map the changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors caused by long-term synaptic depression (LTD) in cerebellar Purkinje cells. LTD produced by pairing parallel fiber activity with depolarization was accompanied by a decline in the response of Purkinje cells to uncaged glutamate that accounted for both the time course and magnitude of LTD. This depression of glutamate responses was observed not only at the site of parallel fiber stimulation but also at more distant sites. The amount of LTD decreased with distance and was half-maximal 50 μm away from the site of parallel fiber activity. Estimation of the number of parallel fibers active during LTD induction indicates that LTD modified glutamate receptors not only at active synapses but also at 600 times as many inactive synapses on a single Purkinje cell. Therefore, both active and inactive parallel fiber synapses can undergo changes at a postsynaptic locus as a result of associative pre- and postsynaptic activity.
A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation
Authors: Skaletskaya Anna , Bartle Laura M. , Chittenden Thomas , McCormick A. Louise , Mocarski Edward S. , Goldmacher Victor S.
Published: July 2002

We have identified a human cytomegalovirus cell-death suppressor, denoted vICA, encoded by the viral
UL36
gene. vICA inhibits Fas-mediated apoptosis by binding to the pro-domain of caspase-8 and preventing its activation. vICA does not share significant sequence homology with FLIPs or other known suppressors of apoptosis, suggesting that this protein represents a new class of cell-death suppressors. Notably, resistance to Fas-mediated apoptosis is delayed in fibroblasts infected with viruses that encode mutant vICA, suggesting that vICA suppresses death-receptor-induced cell death in the context of viral infection. Although vICA is dispensable for viral replication
in vitro
, the common targeting of caspase-8 activation by diverse herpesviruses argues for an important role for this antiapoptotic mechanism in the pathogenesis of viral infection in the host, most likely in avoiding immune clearance by cytotoxic lymphocytes and natural killer cells.
Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit
Authors: Thompson Jill , Kim Daniel F. , O'Connor Michael , Lieberman Kate R. , Bayfield Mark A. , Gregory Steven T. , Green Rachel , Noller Harry F. , Dahlberg Albert E.
Published: July 2002

On the basis of the recent atomic-resolution x-ray structure of the 50S ribosomal subunit, residues A2451 and G2447 of 23S rRNA were proposed to participate directly in ribosome-catalyzed peptide bond formation. We have examined the peptidyltransferase and protein synthesis activities of ribosomes carrying mutations at these nucleotides. In
Escherichia coli
, pure mutant ribosome populations carrying either the G2447A or G2447C mutations maintained cell viability.
In vitro
, the G2447A ribosomes supported protein synthesis at a rate comparable to that of wild-type ribosomes. In single-turnover peptidyltransferase assays, G2447A ribosomes were shown to have essentially unimpaired peptidyltransferase activity at saturating substrate concentrations. All three base changes at the universally conserved A2451 conferred a dominant lethal phenotype when expressed in
E. coli
. Nonetheless, significant amounts of 2451 mutant ribosomes accumulated in polysomes, and all three 2451 mutations stimulated frameshifting and readthrough of stop codons
in vivo
. Furthermore, ribosomes carrying the A2451U transversion synthesized full-length β-lactamase chains
in vitro
. Pure mutant ribosome populations with changes at A2451 were generated by reconstituting
Bacillus stearothermophilus
50S subunits from
in vitro
transcribed 23S rRNA. In single-turnover peptidyltransferase assays, the rate of peptide bond formation was diminished 3- to 14-fold by these mutations. Peptidyltransferase activity and
in vitro
β-lactamase synthesis by ribosomes with mutations at A2451 or G2447 were highly resistant to chloramphenicol. The significant levels of peptidyltransferase activity of ribosomes with mutations at A2451 and G2447 need to be reconciled with the roles proposed for these residues in catalysis.
Nephrocystin interacts with Pyk2, p130
Cas
, and tensin and triggers phosphorylation of Pyk2
Authors: Benzing Thomas , Gerke Peter , Höpker Katja , Hildebrandt Friedhelm , Kim Emily , Walz Gerd
Published: July 2002

Juvenile nephronophthisis type 1 is caused by mutations of
NPHP1
, the gene encoding for nephrocystin. The function
of nephrocystin is presently unknown, but the presence of a Src
homology 3 domain and its recently described interaction with
p130
Cas
suggest that nephrocystin is part of the focal
adhesion signaling complex. We generated a nephrocystin-specific
antiserum and analyzed the interaction of native nephrocystin with
endogenous proteins. Immunoprecipitation of nephrocystin
revealed that nephrocystin forms protein complexes with
p130
Cas
, proline-rich tyrosine kinase 2 (Pyk2), and tensin,
indicating that these proteins participate in a common signaling
pathway. Expression of nephrocystin resulted in phosphorylation of Pyk2
on tyrosine 402 as well as activation of downstream mitogen-activated
protein kinases, such as ERK1 and ERK2. Our findings suggest that
nephrocystin helps to recruit Pyk2 to cell matrix adhesions, thereby
initiating phosphorylation of Pyk2 and Pyk2-dependent signaling. A lack
of functional nephrocystin may compromise Pyk2 signaling in a subset of
renal epithelial cells.
Nociception in cyclooxygenase isozyme-deficient mice
Authors: Ballou Leslie R. , Botting Regina M. , Goorha Sarita , Zhang Jianyi , Vane John R.
Published: July 2002

Prostaglandins formed by cyclooxygenase-1 (COX-1) or COX-2 produce hyperalgesia in sensory nerve endings. To assess the relative roles of the two enzymes in pain processing, we compared responses of COX-1- or COX-2-deficient homozygous and heterozygous mice with wild-type controls in the hot plate and stretching tests for analgesia. Preliminary observational studies determined that there were no differences in gross parameters of behavior between the different groups. Surprisingly, on the hot plate (55°C), the COX-1-deficient heterozygous groups showed less nociception, because mean reaction time was longer than that for controls. All other groups showed similar reaction times. In the stretching test, there was less nociception in COX-1-null and COX-1-deficient heterozygotes and also, unexpectedly, in female COX-2-deficient heterozygotes, as shown by a decreased number of writhes. Measurements of mRNA levels by reverse transcription–PCR demonstrated a compensatory increase of COX-1 mRNA in spinal cords of COX-2-null mice but no increase in COX-2 mRNA in spinal cords of COX-1-null animals. Thus, compensation for the absence of COX-1 may not involve increased expression of COX-2, whereas up-regulation of COX-1 in the spinal cord may compensate for the absence of COX-2. The longer reaction times on the hot plate of COX-1-deficient heterozygotes are difficult to explain, because nonsteroid anti-inflammatory drugs have no analgesic action in this test. Reduction in the number of writhes of the COX-1-null and COX-1-deficient heterozygotes may be due to low levels of COX-1 at the site of stimulation with acetic acid. Thus, prostaglandins made by COX-1 mainly are involved in pain transmission in the stretching test in both male and female mice, whereas those made by COX-2 also may play a role in the stretching response in female mice.
Hemocytes are essential for wing maturation in
Drosophila melanogaster
Authors: Kiger John A. , Natzle Jeanette E. , Green M. M.
Published: July 2002

Newly eclosed flies have wings that are highly folded and compact. Within an hour, each wing has expanded, the dorsal and ventral cuticular surfaces bonding to one another to form the mature wing. To initiate a dissection of this process, we present studies of two mutant phenotypes. First, the
batone
mutant blocks wing expansion, a behavior that is shown to have a mutant focus anterior to the wing in the embryonic fate map. Second, ectopic expression of protein kinase A catalytic subunit (PKAc) using certain
GAL4
enhancer detector strains mimics the
batone
wing phenotype and also induces melanotic “tumors.” Surprisingly, these
GAL4
strains express GAL4 in cells, which seem to be hemocytes, found between the dorsal and ventral surfaces of newly opened wings. Ectopic expression of Ricin A in these cells reduces their number and prevents bonding of the wing surfaces without preventing wing expansion. We propose that hemocytes are present in the wing to phagocytose apoptotic epithelial cells and to synthesize an extracellular matrix that bonds the two wing surfaces together. Hemocytes are known to form melanotic tumors either as part of an innate immune response or under other abnormal conditions, including evidently ectopic PKAc expression. Ectopic expression of PKAc in the presence of the
batone
mutant causes dominant lethality, suggesting a functional relationship. We propose that
batone
is required for the release of a hormone necessary for wing expansion and tissue remodeling by hemocytes in the wing.
Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress
Authors: Paxinou Evgenia , Weisse Marie , Chen Qiping , Souza Jose M. , Hertkorn Caryn , Selak Mary , Daikhin Evgueni , Yudkoff Marc , Sowa Grzegorz , Sessa William C. , Ischiropoulos Harry
Published: July 2002

One of the many biological functions of nitric oxide is the
ability to protect cells from oxidative stress. To investigate the
potential contribution of low steady state levels of nitric oxide
generated by endothelial nitric oxide synthase (eNOS) and the
mechanisms of protection against H
2
O
2
,
spontaneously transformed human ECV304 cells, which normally do not
express eNOS, were stably transfected with a green fluorescent-tagged
eNOS cDNA. The eNOS-transfected cells were found to be resistant to
injury and delayed death following a 2-h exposure to
H
2
O
2
(50–150 μM). Inhibition of nitric oxide
synthesis abolished the protective effect against
H
2
O
2
exposure. The ability of nitric oxide to
protect cells depended on the presence of respiring mitochondria as
ECV304+eNOS cells with diminished mitochondria respiration
(ρ
−
) are injured to the same extent as nontransfected
ECV304 cells and recovery of mitochondrial respiration restores the
ability of nitric oxide to protect against
H
2
O
2
-induced death. Nitric oxide also found to
have a profound effect in cell metabolism, because ECV304+eNOS cells
had lower steady state levels of ATP and higher utilization of glucose
via the glycolytic pathway than ECV304 cells. However, the protective
effect of nitric oxide against H
2
O
2
exposure is
not reproduced in ECV304 cells after treatment with azide and
oligomycin suggesting that the dynamic regulation of respiration by
nitric oxide represent a critical and unrecognized primary line of
defense against oxidative stress.
Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release.
Authors: McMahon H T , Bolshakov V Y , Janz R , Hammer R E , Siegelbaum S A , Südhof T C
Published: July 2002

Synaptophysin (syp I) is a synaptic vesicle membrane protein that constitutes approximately 7% of the total vesicle protein. Multiple lines of evidence implicate syp I in a number of nerve terminal functions. To test these, we have disrupted the murine Syp I gene. Mutant mice lacking syp I were viable and fertile. No changes in the structure and protein composition of the mutant brains were observed except for a decrease in synaptobrevin/VAMP II. Synaptic transmission was normal with no detectable changes in synaptic plasticity or the probability of release. Our data demonstrate that one of the major synaptic vesicle membrane proteins is not essential for synaptic transmission, suggesting that its function is either redundant or that it has a more subtle function not apparent in the assays used.
Gestational drive and the green-bearded placenta.
Authors: Haig D
Published: July 2002

A "green beard" refers to a gene, or group of genes, that is able to recognize itself in other individuals and direct benefits to these individuals. Green-beard effects have been dismissed as implausible by authors who have implicitly assumed sophisticated mechanisms of perception and complex behavioral responses. However, many simple mechanisms for genes to "recognize" themselves exist at the maternal-fetal interface of viviparous organisms. Homophilic cell adhesion molecules, for example, are able to interact with copies of themselves on other cells. Thus, the necessary components of a green-beard effect -- feature, recognition, and response -- can be different aspects of the phenotype of a single gene. Other green-beard effects could involve coalitions of genes at closely linked loci. In fact, any form of epistasis between a locus expressed in a mother and a closely linked locus expressed in the fetus has the property of "self-recognition." Green-beard effects have many formal similarities to systems of meiotic drive and, like them, can be a source of intragenomic conflict.
Pars triangularis asymmetry and language dominance.
Authors: Foundas A L , Leonard C M , Gilmore R L , Fennell E B , Heilman K M
Published: July 2002

The pars triangular is a portion of Broca's area. The convolutions that form the inferior and caudal extent of the pars triangularis include the anterior horizontal and anterior ascending rami of the sylvian fissure, respectively. To learn if there are anatomic asymmetries of the pars triangularis, these convolutions were measured on volumetric magnetic resonance imaging scans of 11 patients who had undergone selective hemispheric anesthesia (Wada testing) to determine hemispheric speech and language lateralization. Of the 10 patients with language lateralized to the left hemisphere, 9 had a leftward asymmetry of the pars triangularis. The 1 patient with language lateralized to the right hemisphere had a significant rightward asymmetry of the pars triangularis. Our data suggest that asymmetries of the pars triangularis may be related to speech-language lateralization.
Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP.
Authors: Ghetti B , Piccardo P , Spillantini M G , Ichimiya Y , Porro M , Perini F , Kitamoto T , Tateishi J , Seiler C , Frangione B , Bugiani O , Giaccone G , Prelli F , Goedert M , Dlouhy S R , Tagliavini F
Published: July 2002

Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).
Molecular basis for decreased muscle chloride conductance in the myotonic goat.
Authors: Beck C L , Fahlke C , George A L
Published: July 2002

Certain forms of myotonia, a condition characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability, are caused by diminished chloride conductance in the muscle cell membrane. We have investigated the molecular basis for decreased muscle chloride conductance in the myotonic goat, an historically important animal model for the elucidation of the role of chloride in muscle excitation. A single nucleotide change causing the substitution of proline for a conserved alanine residue in the carboxyl terminus of the goat muscle chloride channel (gCIC-1) was discovered. Heterologous expression of the mutation demonstrated a substantial (+47 mV) shift in the midpoint of steady-state activation of the channel, resulting in a diminished channel open probability at voltages near the resting membrane potential of skeletal muscle. These results provide a molecular basis for the decreased chloride conductance in myotonic muscle.
A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung.
Authors: Wheeler C J , Felgner P L , Tsai Y J , Marshall J , Sukhu L , Doh S G , Hartikka J , Nietupski J , Manthorpe M , Nichols M , Plewe M , Liang X , Norman J , Smith A , Cheng S H
Published: July 2002

Effective gene therapy for lung tissue requires the use of efficient vehicles to deliver the gene of interest into lung cells. When plasmid DNA encoding chloramphenicol acetyltransferase (CAT) was administered intranasally to BALB/c mice without carrier lipids, CAT activity was detected in mouse lung extracts. Plasmid DNA delivered with optimally formulated commercially available transfection reagents expressed up to 10-fold more CAT activity in lung than observed with naked DNA alone. Liposome formulations consisting of (+/-)-N-(3-aminopropyl)-N,N-dimethyl-2,3-bis (dodecyloxy)-1-propanaminium bromide (GAP-DLRIE) plus the neutral colipid dioleoylphosphatidylethanolamine (DOPE) enhanced CAT expression by more than 100-fold relative to plasmid DNA alone. A single administration of GAP-DLRIE liposome-CAT DNA complexes to mouse lung elicited peak expression at days 1-4 posttransfection, followed by a gradual return to baseline by day 21 postadministration. Readministration of GAP-DLRIE liposome CAT complexes at day 21 led to another transient peak of reporter gene expression. Histological examination of lungs treated with GAP-DLRIE complexed beta-galactosidase DNA revealed that alveolar epithelial cells were the primary locus of expression and that up to 1% of all alveoli contained epithelial cells expressing the transgene.
Blockade of T-cell costimulation prevents development of experimental chronic renal allograft rejection.
Authors: Azuma H , Chandraker A , Nadeau K , Hancock W W , Carpenter C B , Tilney N L , Sayegh M H
Published: July 2002

Blocking CD28-B7 T-cell costimulation by systemic administration of CTLA4Ig, a fusion protein which binds B7 molecules on the surface of antigen-presenting cells, prevents rejection and induces tolerance in experimental acute allograft rejection models. We tested the effect of CTLA4Ig therapy on the process of chronic renal allograft rejection using an established experimental transplantation model. F344 kidneys were transplanted orthotopically into bilaterally nephrectomized LEW recipients. Control animals received low dose cyclosporine for 10 days posttransplantation. Administration of a single injection of CTLA4Ig on day 2 posttransplant alone or in addition to the low dose cyclosporine protocol resulted in improvement of long-term graft survival as compared with controls. More importantly, control recipients which received cyclosporine only developed progressive proteinuria by 8-12 weeks, and morphological evidence of chronic rejection by 16-24 weeks, including widespread transplant arteriosclerosis and focal and segmental glomerulosclerosis, while animals treated with CTLA4Ig alone or in addition to cyclosporine did not. Competitive reverse transcriptase-PCR and immunohistological analysis of allografts at 8, 16, and 24 weeks showed attenuation of lymphocyte and macrophage infiltration and activation in the CTLA4Ig-treated animals, as compared with cyclosporine-alone treated controls. These data confirm that early blockade of the CD28-B7 T-cell costimulatory pathway prevents later development and evolution of chronic renal allograft rejection. Our results indicate that T-cell recognition of alloantigen is a central event in initiating the process of chronic rejection, and that strategies targeted at blocking T-cell costimulation may prove to be a valuable clinical approach to preventing development of the process.
A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.
Authors: Castagliuolo I , Leeman S E , Bartolak-Suki E , Nikulasson S , Qiu B , Carraway R E , Pothoulakis C
Published: July 2002

We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress.
Cotransport of water by the Na
+
/glucose cotransporter
Authors: Loo Donald D. F. , Zeuthen Thomas , Chandy Grischa , Wright Ernest M.
Published: July 2002

Water is transported across epithelial membranes in the absence of
any hydrostatic or osmotic gradients. A prime example is the small
intestine, where 10 liters of water are absorbed each day. Although
water absorption is secondary to active solute transport, the coupling
mechanism between solute and water flow is not understood. We have
tested the hypothesis that water transport is directly linked to solute
transport by cotransport proteins such as the brush border
Na
+
/glucose cotransporter. The Na
+
/glucose
cotransporter was expressed in
Xenopus
oocytes, and the
changes in cell volume were measured under sugar-transporting and
nontransporting conditions. We demonstrate that 260 water molecules are
directly coupled to each sugar molecule transported and estimate that
in the human intestine this accounts for 5 liters of water absorption
per day. Other animal and plant cotransporters such as the
Na
+
/Cl
−
/γ-aminobutyric acid,
Na
+
/iodide and H
+
/amino acid transporters
are also able to transport water and this suggests that cotransporters
play an important role in water homeostasis.