bluuebunny/crossref_metadata_2025 huggingface dataset:
Rigorous treatment of charge exchange, ionization, and collisional processes in neutral-beam-injected mirrors
Authors: Demokan O. , Mirnov V.
Published: July 2002

The ion distribution function is analytically studied in mirror machines with perpendicular injection. A uniform model is considered by assuming a square-well configuration for the magnetic field. The existence of the mirrors and the consequent electrostatic potential are represented by related boundary conditions on the ion distribution function. The Vlasov–Boltzmann equation is written with the explicit expressions for the charge exchange, electron impact ionization, ion–electron collision processes and solved for the steady state. The justification for neglecting the ion–ion collisions is provided.
The free electron laser–peniotron hybrid: Physics and features
Authors: Gong J. M. , Boscolo I. , Liu S. G.
Published: July 2002

The free electron laser–peniotron hybrid is studied. It is shown by computer simulations that the free electron laser–peniotron hybrid, with the synchronous condition ω−(kw+k∥)v∥−ωc≊0, is a strong interaction, and has an efficiency as high as that of the peniotron. The interaction of the free electron laser–peniotron hybrid is compared with that of the free electron laser–cyclotron hybrid.
The linear theory of cyclotron resonance masers with trochoidal electron beams
Authors: Nusinovich G. S.
Published: July 2002

Cyclotron resonance masers are considered in which electrons propagate along trochoidal trajectories in crossed external electric and magnetic fields. A potential advantage of these devices is the small spread in electron axial velocities in the absence of space charge effects that facilitates operation at traveling waves. In this paper some general relations between parameters of these devices are analyzed and the effect of beam current density on axial velocity spread is studied. The linear theory of such devices operating at traveling waves is presented and the amplification of some specific modes in a rectangular waveguide is analyzed.
On the ballooning equation for toroidal drift type modes
Authors: Hirose A. , Smolyakov A. I.
Published: July 2002

The ballooning equation for drift type modes in tokamaks is shown to be of fourth order when the ion temperature gradient is finite. Fluid-like ion density perturbation is formulated for arbitrary ωDi (the ion magnetic drift frequency) and k∥vTi (the ion transit frequency). It recovers the gyro-kinetic counterpart with satisfactory accuracy.
Impact of radial transport on the quasilinear plateau formation due to electron cyclotron wave absorption
Authors: Peeters A. G. , Westerhof E.
Published: July 2002

Numerical simulations using a three-dimensional Fokker–Planck code show that for small tokamaks the transport of electrons across the magnetic surfaces at a level consistent with anomalous transport has a large influence on the formation of the quasilinear plateau during electron cyclotron resonant heating. The reduction of wave absorption due to the plateau formation is much smaller when the effects of radial transport are included. This is explained by the localized nature of the resonance in velocity space and the strong dependence of resonant energy on radial position. Impact of the effect on diagnostic signals is discussed.
Magnetic fluctuation driven cross-field particle transport in the reversed-field pinch
Authors: Scheffel Jan , Liu Donghui
Published: July 2002

Electrostatic and electromagnetic fluctuations generally cause cross-field particle transport in confined plasmas. Thus core localized turbulence must be kept at low levels for sufficient energy confinement in magnetic fusion plasmas. Reversed-field pinch (RFP) equilibria can, theoretically, be completely stable to ideal and resistive (tearing) magnetohydrodynamic (MHD) modes at zero beta. Unstable resistive interchange modes are, however, always present at experimentally relevant values of the poloidal beta βθ. An analytical quasilinear, ambipolar diffusion model is here used to model associated particle transport. The results indicate that core density fluctuations should not exceed a level of about 1% for plasmas of fusion interest. Parameters of experimentally relevant stationary states of the RFP were adjusted to minimize growth rates, using a fully resistive linearized MHD stability code. Density gradient effects are included through employing a parabolic density profile. The scaling of particle diffusion [D(r)∝λ2n0.5T/aB, where λ is the mode width] is such that the effects of particle transport are milder in present day RFP experiments than in future reactor-relevant plasmas.
Variational estimates of changes in neutral-plasma reaction rates
Authors: Stacey W. M.
Published: July 2002

A variational estimate of the change in a neutral-plasma reaction rate due to a change in plasma properties is presented. The effect of the change in neutral distribution which would result from a change in plasma properties is taken into account in the estimate, without the need for a recomputation of the neutral distribution. The general methodology is specialized to a neutral diffusion theory model and a numerical example is presented for a representative divertor problem. Application to reduce the computational time for coupled plasma-neutral calculations is discussed.
Volume recombination and opacity in Alcator C-Mod divertor plasmas
Authors: Terry J. L. , Lipschultz B. , Pigarov A. Yu. , Krasheninnikov S. I. , LaBombard B. , Lumma D. , Ohkawa H. , Pappas D. , Umansky M.
Published: July 2002

Volume recombination within the Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] divertor plasma is measured and found to be a significant fraction of the total ion sink under detached divertor conditions. The recombination occurs in regions where Te∼1 eV and ne∼1021 m−3. Measurements of the spatial distribution of the recombination are presented. The determinations of the recombination rates are made by measuring the D0 Balmer spectrum and by using a collisional radiative model describing the level populations, ionization, and recombination of D0. The concept of “recombinations per Balmer series photon” is developed to simplify the determinations. Measurements of the opacity of Lyβ emission are presented. It is observed that up to 50% of the Lyβ emission is trapped, indicating that Lyα is strongly trapped in some cases. The effects of Lyα,β trapping on the “recombinations per photon” curves are calculated and considered in the recombination rate determinations. Observations indicating the presence of molecular activated recombination are discussed.
Linear and nonlinear dust-acoustic waves in inhomogeneous dusty plasmas
Authors: Singh S. V. , Rao N. N.
Published: July 2002

The propagation of linear, as well as nonlinear, dust-acoustic waves in inhomogeneous dusty plasmas consisting of electrons, ions, and charged dust particles is investigated. It is shown that the amplitude of the dust-acoustic waves is affected by the presence of the dust density inhomogeneity. Amplitudes of the linear and nonlinear dust-acoustic waves decrease (increase) as the waves propagate in the direction of increasing (decreasing) density. The wave amplitude is inversely proportional to the square root of the dust particle’s density for the linear dust-acoustic waves. In the nonlinear case, to the lowest order and for the cold dust species, the wave amplitude is found to be directly proportional to nd0−1/4. Various special cases are explicitly considered, and comparison with the corresponding results for the usual two-component electron-ion plasmas is also carried out.
Experimental studies of plasma transport across a magnetic island in the Compact Auburn Torsatron
Authors: Gandy R. F. , Cooney J. , Forester D. , Knowlton S. , Watts C.
Published: July 2002

A set of experiments on the Compact Auburn Torsatron [Gandy et al., Fusion Technol. 18, 281 (1990)] has investigated plasma particle transport properties across a magnetic island. The size of the island was systematically varied and the resulting changes in plasma transport were determined. Measurements of plasma density, electron and ion temperature, and plasma rotation speed were performed. Using a simple diffusion model, these measurements were used to deduce the diffusion coefficients for ions and electrons. With a factor of 2 increase in island width, the ion diffusion coefficient remained nearly constant whereas the electron diffusion coefficient increased by a factor of 4.
A theoretical analysis on electrostatic lower-hybrid wave propagation in plasmas with magnetic ripple: Nonlinear oscillations, resonances, ray tracing, and spectral gap
Authors: Bizarro João P. S. , Ferreira Jorge S. , Nakach Roland
Published: July 2002

The analytical expression for the frequency of the unperturbed radial electrostatic lower-hybrid (LH) ray oscillations is derived, which constitutes the first analytically calculable result in nonlinear LH ray dynamics. For LH current drive (CD) conditions, and after comparing the frequency of the unperturbed LH ray motion with the frequency of the ripple perturbation, it is concluded that the electrostatic LH ray dynamics is generally regular in cylindrical plasmas with magnetic ripple. It is also found analytically that including the magnetic ripple in ray-tracing calculations does not lead to a final closure of the spectral-gap problem for LHCD in circular-poloidal-cross-section tokamaks having sufficiently low electron density, in addition to a high enough aspect ratio and safety factor, in which case electrostatic LH wave propagation turns out to be independent of the latter, and the unperturbed LH ray oscillations become basically linear. This is an important null result that helps to show that the conventional ray-tracing picture widely used in LHCD modeling (that is to say, a standardly coupled LH spectrum propagating according to geometrical optics in an established tokamak equilibrium) is not to be taken as final. The analysis presented, carried out within an explicitly Hamiltonian formalism and addressing the role of resonances between the frequency of the unperturbed LH ray motion and the frequencies of the perturbations due to magnetic ripple and toroidicity, is detailed and careful, with analytical results and conclusions being supported by numerical calculations.
Whistler solitons in plasma with anisotropic hot electron admixture
Authors: Khazanov G. V. , Krivorutsky E. N. , Gallagher D. L.
Published: July 2002

The longitudinal and transverse modulation instability of whistler waves in plasma, with a small admixture of hot anisotropic electrons, is discussed. If the hot particles temperature anisotropy is positive, it is found that, in such plasma, longitudinal perturbations can lead to soliton formation for frequencies forbidden in cold plasma. The soliton is enriched by hot particles. The frequency region unstable to transverse modulation in cold plasma in the presence of hot electrons is divided by stable domains. For both cases the role of hot electrons is more significant for whistlers with smaller frequencies.
Effect of poloidally asymmetric sheared flow on resistive ballooning turbulence
Authors: Garcia L. , Carreras B. A. , Lynch V. E.
Published: July 2002

The shear flow induced through the Reynolds stress tensor by turbulence with ballooning character is poloidally asymmetric. For circular cross section tokamak plasmas, its main component is the (m=1, n=0). The effect of such a sheared flow on both linear and nonlinear instability is analyzed. Its effect on the linear stability properties of resistive ballooning modes is compared with the effect of poloidally symmetric sheared flows. It is shown that asymmetry in the flow does not reduce its effectiveness in stabilizing the linear resistive ballooning modes. It is also effective in reducing the turbulence level and decreasing the turbulence induced diffusivities.
Acousto-electro-optic light modulation
Authors: Psaltis Demetri , Lee Hyuk , Sirat Gabriel
Published: July 2002

The acousto-electro-optic effect is analyzed and demonstrated experimentally. The application of the acousto-electro-optic effect to light modulation and deflection is discussed.
Tunneling currents and two-body effects in quantum well and superlattice structures
Authors: Coon D. D. , Liu H. C.
Published: July 2002

Direct current (dc) tunneling through a finite superlattice or quantum well structure is analyzed in an independent particle model. A correction is made to the Tsu–Esaki [Appl. Phys. Lett. 22, 562 (1973)] one-particle current expression. In addition, a two-body current term is found which can, in some cases, be of the same order of magnitude as the one-particle current terms of Tsu and Esaki.
Optical nonlinearity resulting from mobile carriers in semiconductor superlattices: Influence of higher minibands
Authors: de Sterke C. M. , Hall D. G.
Published: July 2002

We have investigated the temperature dependence of χ(3) optical nonlinearities associated with mobile carriers in a superlattice. Our computer calculations show that at temperatures near 300 K, the population of higher minibands can significantly increase χ(3) over that predicted by considering only the lowest miniband. The magnitude of this increase is strongly correlated with the layer configuration of the superlattice and its associated band structure.
Sensitive detection of NO2 using high-frequency heterodyne spectroscopy with a GaAlAs diode laser
Authors: Lenth W. , Gehrtz M.
Published: July 2002

Optical heterodyne spectroscopy has been performed by modulating the injection of a GaAlAs diode laser at 250 MHz. Sensitive and fast detection of NO2 was accomplished using phase-sensitive detection electronics. By proper adjustment of the local oscillator phase the heterodyne beat signal induced by NO2 absorption lines could be detected against zero background. A minimum NO2 absorption of 1×10−6 was measured with an effective bandwidth of 6 Hz. Increasing the detection bandwidth and scanning the diode laser very rapidly permitted detection of 5×10−4 absorption on a 100-ns time scale. The obtained results demonstrate that optical heterodyne spectroscopy with current modulated diode lasers offers the high sensitivity and fast time response required for the detection of gaseous species in pollution studies, combustion control, and industrial process monitoring.
Preparation and electrical properties of InPxOy gate insulators on InP
Authors: Chang H. L. , Meiners L. G. , Sa C. J.
Published: July 2002

A new insulating film, InPxOy, has been deposited in an indirect plasma-enhanced low-pressure chemical vapor deposition system for use as a gate dielectric layer on InP. In this system the oxygen is excited in an rf plasma chamber which is separated from the deposition chamber to avoid radiation damage to the InP surfaces. Triethylindium (TEI) and PH3 were used as sources for indium and phosphorus, respectively. A two-zone furnace was employed in which PH3 was decomposed in the high-temperature (800 °C) zone, whereas deposition was carried out in the low-temperature (300 °C) zone. The electrical properties of the deposited films are dependent, to a large extent, upon the ratio of TEI vapor to PH3 during deposition. The resistivities range from 1013 to 1015 Ω cm. Fast interface state densities as determined from capacitance-voltage (C-V) measurements of layers deposited on n-type InP substrates exhibit minima as low as 1010 cm−2 eV−1. The hysteresis in the high-frequency C-V curves was as low as 0.2 V, indicating that the densities of the slow states were reduced to a very low level due, probably, to the structural compatibility between the deposited layer and the InP substrates.
Layer intermixing in HgTe-CdTe superlattices
Authors: Arch David K. , Staudenmann J. L. , Faurie J. P.
Published: July 2002

High-temperature x-ray diffraction measurements on HgTe-CdTe superlattices grown by molecular beam epitaxy have been made to determine the extent of intermixing of the individual HgTe and CdTe layers. In situ interdiffusion measurements were carried out at 110, 162, and 185 °C and estimates of the interdiffusion coefficient were made. We find appreciable intermixing of the HgTe and CdTe layers at temperatures as low as 110 °C. Such results have serious implications for the use of this material in optoelectronic devices.
Single longitudinal mode operation of semiconductor laser arrays with étalon feedback
Authors: Hemmati H.
Published: July 2002

The multiple longitudinal mode output of high-power diode-laser arrays is converted into single mode with 97% efficiency by optical feedback from a thin (<200 μm thick) étalon external to the laser. The coupled cavities formed by addition of the étalon favor a single longitudinal mode. Single-mode operation is retained at 0.1 MHz pulsed rates. Both the near-field and the far-field patterns of the laser array remain nearly unchanged while the array operates in a single longitudinal mode.
Single-crystal x-ray diffraction study of the InGaAs-GaAsP/GaAs superlattice system
Authors: Jiang B-L. , Shimura F. , Rozgonyi G. A. , Hamaguchi N. , Bedair S. M.
Published: July 2002

Single-crystal x-ray rocking curve and transmission imaging topography techniques have been used for the characterization of InGaAs-GaAsP strained-layer superlattices (SLS’s), which are lattice matched to GaAs substrates. The thicknesses of the SLS’s and strains, 〈ε⊥〉 and 〈ε∥〉, were readily determined nondestructively by analyzing the rocking curves obtained with Cu Kβ1 radiation. These quantitative data were combined with the qualitative defect imaging results of x-ray topography to determine the critical intrinsic SLS thickness tISc (=PSL〈ε̄∥〉c) that dominates the generation of misfit dislocations. It was estimated for the InGaAs-GaAsP SLS on a GaAs substrate as 1.05×10−3 Å<tISc<1.56×10−3 Å.
Erratum: Low-temperature epitaxial growth of silicon by low-pressure chemical vapor deposition [Appl. Phys. Lett. 5
2, 1053 (1988)]
Authors: Meakin D. , Stobbs M. , Stoemenos J. , Economou N. A.
Published: July 2002

Low-pressure chemical deposition of silicon by the pyrolysis of pure silane at relatively low temperatures and pressures below 100 mTorr can lead to structurally well-defined films. Below 10 mTorr the films exhibit evidence of local epitaxial growth, which can be particularly well defined on Si(100) wafers chemically treated prior to deposition outside the deposition chamber. Even so, the interface was found to be highly strained, and high-resolution electron microscopy observations were used to analyze the defect structures in the epitaxial layer as initiated at the interface.
The glycosynapse
Authors: Hakomori Sen-itiroh
Published: July 2002

Physically distinguishable microdomains associated with various functional membrane proteins are one of the major current topics in cell biology. Glycosphingolipids present in such microdomains have been used as “markers;” however, the functional role of glycosyl epitopes in microdomains has received little attention. In this review, I have tried to summarize the evidence that glycosyl epitopes in microdomains mediate cell adhesion and signal transduction events that affect cellular phenotypes. Molecular assemblies that perform such functions are hereby termed “glycosynapse” in analogy to “immunological synapse,” the membrane assembly of immunocyte adhesion and signaling. Three types of glycosynapses are so far distinguishable: (i) Glycosphingolipids organized with cytoplasmic signal transducers and proteolipid tetraspanin with or without growth factor receptors; (ii) transmembrane mucin-type glycoproteins with clustered O-linked glycoepitopes for cell adhesion and associated signal transducers at lipid domain; and (iii) N-glycosylated transmembrane adhesion receptors complexed with tetraspanin and gangliosides, as typically seen with the integrin–tetraspanin–ganglioside complex. The possibility is discussed that glycosynapses give rise to a high degree of diversity and complexity of phenotypes.
Coupling asymmetry of heterotypic connexin 45/ connexin 43-EGFP gap junctions: Properties of fast and slow gating mechanisms
Authors: Bukauskas Feliksas F. , Bukauskiene Angele , Verselis Vytas K. , Bennett Michael V. L.
Published: July 2002

Although fast and slow gating mechanisms have been described in gap junctions (GJs), their relative contributions to dependence on transjunctional voltage,
V
j
, is still unclear. We used cell lines expressing wild-type connexin 45 (Cx45) and connexin 43 fused with enhanced green fluorescent protein (Cx43-EGFP) to examine mechanisms of gating in homo- and heterotypic GJs formed of these connexins. Macroscopically Cx45/Cx45 channels show high sensitivity to
V
j
. Cx45 channels demonstrate two types of gating: fast transitions between open and residual states and slow transitions between open and completely closed states. Single-channel conductance of the Cx45 channel is ≈32 pS for the open state and ≈4 pS for the residual state. Cx45/Cx43-EGFP heterotypic junctions exhibit very asymmetrical
V
j
gating with the maximum junctional conductance shifted to
V
j
positive on the Cx45 side. Conductance of single Cx45/Cx43-EGFP channels is ≈55 pS for the open state and ≈4 pS for the residual state, values consistent with the simple-series connection of Cx45 and Cx43-EGFP hemichannels. At
V
j
= 0, the slow gate of many Cx45 hemichannels is closed in both homotypic Cx45/Cx45 and heterotypic Cx45/Cx43-EGFP junctions. Fast and slow
V
j
gates of both Cx45 and Cx43 hemichannels close for relative negativity at their cytoplasmic end. Coupling mediated by Cx45/Cx43-EGFP junctions can exhibit asymmetry that can be strongly modulated by small changes in difference of holding potentials. Cx45/Cx43 junctions are likely to be found in brain and heart and may mediate rectifying electrical transmission or modulatable chemical communication.
Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study
Authors: Vuilleumier Patrik , Sagiv Noam , Hazeltine Eliot , Poldrack Russel A. , Swick Diane , Rafal Robert D. , Gabrieli John D. E.
Published: July 2002

To compare neural activity produced by visual events that escape or
reach conscious awareness, we used event-related MRI and evoked
potentials in a patient who had neglect and extinction after focal
right parietal damage, but intact visual fields. This neurological
disorder entails a loss of awareness for stimuli in the field
contralateral to a brain lesion when stimuli are simultaneously
presented on the ipsilateral side, even though early visual areas may
be intact, and single contralateral stimuli may still be perceived.
Functional MRI and event-related potential study were performed during
a task where faces or shapes appeared in the right, left, or both
fields. Unilateral stimuli produced normal responses in V1 and
extrastriate areas. In bilateral events, left faces that were not
perceived still activated right V1 and inferior temporal cortex and
evoked nonsignificantly reduced N1 potentials, with preserved
face-specific negative potentials at 170 ms. When left faces were
perceived, the same stimuli produced greater activity in a distributed
network of areas including right V1 and cuneus, bilateral fusiform
gyri, and left parietal cortex. Also, effective connectivity between
visual, parietal, and frontal areas increased during perception of
faces. These results suggest that activity can occur in V1 and ventral
temporal cortex without awareness, whereas coupling with dorsal
parietal and frontal areas may be critical for such activity to afford
conscious perception.
Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells
Authors: Teng Yang D. , Lavik Erin B. , Qu Xianlu , Park Kook I. , Ourednik Jitka , Zurakowski David , Langer Robert , Snyder Evan Y.
Published: July 2002

To better direct repair following spinal cord injury (SCI), we designed an implant modeled after the intact spinal cord consisting of a multicomponent polymer scaffold seeded with neural stem cells. Implantation of the scaffold–neural stem cells unit into an adult rat hemisection model of SCI promoted long-term improvement in function (persistent for 1 year in some animals) relative to a lesion-control group. At 70 days postinjury, animals implanted with scaffold-plus-cells exhibited coordinated, weight-bearing hindlimb stepping. Histology and immunocytochemical analysis suggested that this recovery might be attributable partly to a reduction in tissue loss from secondary injury processes as well as in diminished glial scarring. Tract tracing demonstrated corticospinal tract fibers passing through the injury epicenter to the caudal cord, a phenomenon not present in untreated groups. Together with evidence of enhanced local GAP-43 expression not seen in controls, these findings suggest a possible regeneration component. These results may suggest a new approach to SCI and, more broadly, may serve as a prototype for multidisciplinary strategies against complex neurological problems.
Interaction of RNA polymerase with forked DNA: Evidence for two kinetically significant intermediates on the pathway to the final complex
Authors: Tsujikawa Laura , Tsodikov Oleg V. , deHaseth Pieter L.
Published: July 2002

RNA polymerase forms competitor-resistant complexes with “forked DNA” templates that are double-stranded from the −35 promoter region through the first base pair of the −10 region, with an additional unpaired A at the 3′ end of the nontemplate strand. These types of substrates were introduced recently as model templates for the study of DNA–protein interactions occurring in the early stages of the formation of RNA polymerase–promoter open complexes. We have performed kinetic and equilibrium measurements of interactions of wild-type and mutant RNA polymerases bearing substitutions in the σ
70
initiation factor, with forked DNA of wild-type and mutant sequence. Our observations reveal that formation of a competitor-resistant complex between RNA polymerase and forked DNA, similar to the formation of open complexes at promoters, is a multistep process, and some of the sequentially formed intermediates along the two pathways share common properties. This work establishes, for the forked template, progression through these intermediates in the absence of downstream DNA and validates the use of forked DNA to determine the effects of changes in promoter or RNA polymerase sequence on the process of open complex formation.
Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival
Authors: Meucci Olimpia , Fatatis Alessandro , Simen Arthur A. , Miller Richard J.
Published: July 2002

Recentin vitroandin vivostudies have shown that the chemokine fractalkine is widely expressed in the brain and localized principally to neurons. Central nervous system expression of CX3CR1, the only known receptor for fractalkine, has been demonstrated exclusively on microglia and astrocytes. Thus, it has been proposed that fractalkine regulates cellular communication between neurons (that produce fractalkine) and microglia (that express its receptor). Here we show, for the first time, that hippocampal neurons also express CX3CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-κB, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120IIIB, an effect blocked by anti-CX3CR1 antibodies. Experiments with two different inhibitors of the phosphatidylinositol 3-kinase, a key enzyme in the activation of Akt, and with a phospholipid activator of Akt demonstrate that Akt activation is responsible for the neuroprotective effects of fractalkine. These data show that neuronal CX3CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia.
Glutamate antagonists limit tumor growth
Authors: Rzeski Wojciech , Turski Lechoslaw , Ikonomidou Chrysanthy
Published: July 2002

Neuronal progenitors and tumor cells possess propensity to
proliferate and to migrate. Glutamate regulates proliferation and
migration of neurons during development, but it is not known whether it
influences proliferation and migration of tumor cells. We demonstrate
that glutamate antagonists inhibit proliferation of human tumor cells.
Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells
were most sensitive to the antiproliferative effect of the
N
-methyl-
d
-aspartate antagonist dizocilpine,
whereas breast and lung carcinoma, colon adenocarcinoma, and
neuroblastoma cells responded most favorably to the
α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist
GYKI52466. The antiproliferative effect of glutamate antagonists was
Ca
2+
dependent and resulted from decreased cell division
and increased cell death. Morphological alterations induced by
glutamate antagonists in tumor cells consisted of reduced membrane
ruffling and pseudopodial protrusions. Furthermore, glutamate
antagonists decreased motility and invasive growth of tumor cells.
These findings suggest anticancer potential of glutamate antagonists.
Inhibition of
Escherichia coli
viability by external guide sequences complementary to two essential genes
Authors: McKinney Jeffrey , Guerrier-Takada Cecilia , Wesolowski Donna , Altman Sidney
Published: July 2002

Narrow spectrum antimicrobial activity has been designed to reduce
the expression of two essential genes, one coding for the protein
subunit of RNase P (C5 protein) and one for gyrase (gyrase A). In both
cases, external guide sequences (EGS) have been designed to complex
with either mRNA. Using the EGS technology, the level of microbial
viability is reduced to less than 10% of the wild-type strain. The
EGSs are additive when used together and depend on the number of
nucleotides paired when attacking gyrase A mRNA. In the case of gyrase
A, three nucleotides unpaired out of a 15-mer EGS still favor complete
inhibition by the EGS but five unpaired nucleotides do not.
NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension
Authors: Fiorucci Stefano , Antonelli Elisabetta , Morelli Olivia , Mencarelli Andrea , Casini Alessandro , Mello Tommaso , Palazzetti Barbara , Tallet Dominique , del Soldato Piero , Morelli Antonio
Published: July 2002

Portal hypertension resulting from increased intrahepatic resistance is a common complication of chronic liver diseases and a leading cause of death in patients with liver cirrhosis, a scarring process of the liver that includes components of both increased fibrogenesis and wound contraction. A reduced production of nitric oxide (NO) resulting from an impaired enzymatic function of endothelial NO synthase and an increased contraction of hepatic stellate cells (HSCs) have been demonstrated to contribute to high intrahepatic resistance in the cirrhotic liver. 2-(Acetyloxy) benzoic acid 3-(nitrooxymethyl) phenyl ester (NCX-1000) is a chemical entity obtained by adding an NO-releasing moiety to ursodeoxycholic acid (UDCA), a compound that is selectively metabolized by hepatocytes. In this study we have examined the effect of NCX-1000 and UDCA on liver fibrosis and portal hypertension induced by i.p. injection of carbon tetrachloride in rats. Our results demonstrated that although both treatments reduced liver collagen deposition, NCX-1000, but not UDCA, prevented ascite formation and reduced intrahepatic resistance in carbon tetrachloride-treated rats as measured by assessing portal perfusion pressure. In contrast to UDCA, NCX-1000 inhibited HSC contraction and exerted a relaxing effect similar to the NO donor
S
-nitroso-
N
-acetylpenicillamine. HSCs were able to metabolize NCX-1000 and release nitrite/nitrate in cell supernatants. In aggregate these data indicate that NCX-1000, releasing NO into the liver microcirculation, may provide a novel therapy for the treatment of patients with portal hypertension.
Transgenic rescue implicates β2-microglobulin as a diabetes susceptibility gene in nonobese diabetic (NOD) mice
Authors: Hamilton-Williams Emma E. , Serreze David V. , Charlton Brett , Johnson Ellis A. , Marron Michele P. , Müllbacher Arno , Slattery Robyn M.
Published: July 2002

Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from T-cell-mediated autoimmune destruction of insulin-producing pancreatic β cells. Linkage studies have shown that type 1 diabetes in NOD mice is a polygenic disease involving more than 15 chromosomal susceptibility regions. Despite extensive investigation, the identification of individual susceptibility genes either within or outside the major histocompatibility complex region has proven problematic because of the limitations of linkage analysis. In this paper, we provide evidence implicating a single diabetes susceptibility gene, which lies outside the major histocompatibility complex region. Using allelic reconstitution by transgenic rescue, we show that NOD mice expressing the β2microglobulin (β2M)aallele develop diabetes, whereas NOD mice expressing a murine β2Mbor human allele are protected. The murine β2Maallele differs from the β2Mballele only at a single amino acid. Mechanistic studies indicate that the absence of the NOD β2Maisoform on nonhematopoietic cells inhibits the development or activation of diabetogenic T cells.
ROP-1, an RNA quality-control pathway component, affectsCaenorhabditis elegansdauer formation
Authors: Labbé Jean-Claude , Burgess Jason , Rokeach Luis A. , Hekimi Siegfried
Published: July 2002

Caenorhabditis elegansdauer formation is an alternative larval developmental pathway that the worm can take when environmental conditions become detrimental. Animals can survive several months in this stress-resistant stage and can resume normal development when growth conditions improve. Although the worms integrate a variety of sensory information to commit to dauer formation, it is currently unknown whether they also monitor internal cellular damage. The Ro ribonucleoprotein complex, which was initially described as a human autoantigen, is composed of one major 60-kDa protein, Ro60, that binds to one of four small RNA molecules, designated Y RNAs. Ro60 has been shown to bind mutant 5S rRNA molecules inXenopusoocytes, suggesting a role for Ro60 in 5S rRNA biogenesis. Analysis of ribosomes from aC. elegans rop-1(−) strain, which is null for the expression of Ro60, demonstrated that they contain a high percentage of mutant 5S rRNA molecules, thereby strengthening the notion of a link between therop-1gene product and 5S rRNA quality control. The Ro particle was recently shown to be involved in the resistance ofDeinococcus radioduransto UV irradiation, suggesting a role for the Ro complex in stress resistance. We have studied the role ofrop-1in dauer formation. We present genetic and biochemical evidence thatrop-1interacts with dauer-formation genes and is involved in the regulation of the worms' entry into the dauer stage. Furthermore, we find that therop-1gene product undergoes a proteolytic processing step that is regulated by the dauer formation pathway via an aspartic proteinase. These results suggest that the Ro particle may function in an RNA quality-control checkpoint for dauer formation.
Crystal structure of thermostable DNA photolyase: Pyrimidine-dimer recognition mechanism
Authors: Komori Hirofumi , Masui Ryoji , Kuramitsu Seiki , Yokoyama Shigeyuki , Shibata Takehiko , Inoue Yorinao , Miki Kunio
Published: July 2002

DNA photolyase is a pyrimidine-dimer repair enzyme that uses visible light. Photolyase generally contains two chromophore cofactors. One is a catalytic cofactor directly contributing to the repair of a pyrimidine-dimer. The other is a light-harvesting cofactor, which absorbs visible light and transfers energy to the catalytic cofactor. Photolyases are classified according to their second cofactor into either a folate- or deazaflavin-type. The native structures of both types of photolyases have already been determined, but the mechanism of substrate recognition remains largely unclear because of the lack of structural information regarding the photolyase-substrate complex. Photolyase from
Thermus thermophilus
, the first thermostable class I photolyase found, is favorable for function analysis, but even the type of the second cofactor has not been identified. Here, we report the crystal structures of
T. thermophilus
photolyase in both forms of the native enzyme and the complex along with a part of its substrate, thymine. A structural comparison with other photolyases suggests that
T. thermophilus
photolyase has structural features allowing for thermostability and that its light-harvesting cofactor binding site bears a close resemblance to a deazaflavin-type photolyase. One thymine base is found at the hole, a putative substrate-binding site near the catalytic cofactor in the complex form. This structural data for the photolyase-thymine complex allow us to propose a detailed model for the pyrimidine-dimer recognition mechanism.
Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling.
Authors: Ravichandran K S , Igras V , Shoelson S E , Fesik S W , Burakoff S J
Published: July 2002

Stimulation via the T-cell growth factor interleukin 2 (IL-2) leads to tyrosine phosphorylation of Shc, the interaction of Shc with Grb2, and the Ras GTP/GDP exchange factor, mSOS. Shc also coprecipitates with the IL-2 receptor (IL-2R), and therefore, may link IL-2R to Ras activation. We have further characterized the Shc-IL-2R interaction and have made the following observations. (i) Among the two phosphotyrosine-interaction domains present in Shc, the phosphotyrosine-binding (PTB) domain, rather than its SH2 domain, interacts with the tyrosine-phosphorylated IL-2R beta chain. Moreover, the Shc-PTB domain binds a phosphopeptide derived from the IL-2R beta chain (corresponding to residues surrounding Y338, SCFTNQGpYFF) with high affinity. (ii) In vivo, mutant IL-2R beta chains lacking the acidic region of IL-2Rbeta (which contains Y338) fail to phosphorylate Shc. Furthermore, when wild type or mutant Shc proteins that lack the PTB domain were expressed in the IL-2-dependent CTLL-20 cell line, an intact Shc-PTB domain was required for Shc phosphorylation by the IL-2R, which provides further support for a Shc-PTB-IL-2R interaction in vivo. (iii) PTB and SH2 domains of Shc associate with different proteins in IL-2- and T-cell-receptor-stimulated lysates, suggesting that Shc, through the concurrent use of its two different phosphotyrosine-binding domains, could assemble multiple protein complexes. Taken together, our in vivo and in vitro observations suggest that the PTB domain of Shc interacts with Y338 of the IL-2R and provide evidence for a functional role for the Shc-PTB domain in IL-2 signaling.
Trans-activation by human immunodeficiency virus Tat protein requires the C-terminal domain of RNA polymerase II.
Authors: Okamoto H , Sheline C T , Corden J L , Jones K A , Peterlin B M
Published: July 2002

Human immunodeficiency virus (HIV)-encoded trans-activator (Tat) acts through the trans-activation response element RNA stem-loop to increase greatly the processivity of RNA polymerase II. Without Tat, transcription originating from the HIV promoter is attenuated. In this study, we demonstrate that transcriptional activation by Tat in vivo and in vitro requires the C-terminal domain (CTD) of RNA polymerase II. In contrast, the CTD is not required for basal transcription and for the formation of short, attenuated transcripts. Thus, trans-activation by Tat resembles enhancer-dependent activation of transcription. These results suggest that effects of Tat on the processivity of RNA polymerase II require proteins that are associated with the CTD and may result in the phosphorylation of the CTD.
Interaction of pigeon cytochromec-(43–58) peptide analogs with either T cell antigen receptor or I-Ab molecule
Authors: Itoh Yasushi , Kajino Kiichi , Ogasawara Kazumasa , Takahashi Akio , Namba Ken-ichi , Negishi Izumi , Matsuki Naoto , Iwabuchi Kazuya , Kakinuma Mitsuaki , Good Robert A. , Onoé Kazunori
Published: July 2002

We determined that a pigeon cytochromec-derived peptide, p43–58, possesses two anchor residues, 46 and 54, for binding with the I-Abmolecule that are compatible to the position 1 (P1) and position 9 (P9) of the core region in the major histocompatibility complex (MHC) class II binding peptides, respectively. In the present study to analyze each binding site between P1 and P9 of p43–58 to either I-Abor T cell antigen receptor (TCR), we investigated T cell responses to a series of peptides (P2K, P3K, P4K, P5K, P6K, P7K, and P8E) that sequentially substituted charged amino acid residues for the residues at P2 to P8 of p43–58. T cells from C57BL/10 (I-Ab) mice immunized with P4K or P6K did not mount appreciable proliferative responses to the immunogens, but those primed with other peptides (P2K, P3K, P5K, P7K, and P8E) showed substantial responses in an immunogen-specific manner. It was demonstrated by binding studies that P1 and P9 functioned as main anchors and P4 and P6 functioned as secondary anchors to I-Ab. Analyses of Vβ usage of T cell lines specific for these analogs suggested that P8 interacts with the complementarity-determining region 1 (CDR1)/CDR2 of the TCR β chain. Furthermore, sequencing of the TCR on T cell hybridomas specific for these analogs indicated that P5 interacts with the CDR3 of the TCR β chain. The present findings are consistent with the three-dimensional structure of the trimolecular complex that has been reported for TCR/peptide/MHC class I molecules.
Cell locomotion and focal adhesions are regulated by substrate flexibility
Authors: Pelham Robert J. , Wang Yu-li
Published: July 2002

Responses of cells to mechanical properties of the adhesion substrate were examined by culturing normal rat kidney epithelial and 3T3 fibroblastic cells on a collagen-coated polyacrylamide substrate that allows the flexibility to be varied while maintaining a constant chemical environment. Compared with cells on rigid substrates, those on flexible substrates showed reduced spreading and increased rates of motility or lamellipodial activity. Microinjection of fluorescent vinculin indicated that focal adhesions on flexible substrates were irregularly shaped and highly dynamic whereas those on firm substrates had a normal morphology and were much more stable. Cells on flexible substrates also contained a reduced amount of phosphotyrosine at adhesion sites. Treatment of these cells with phenylarsine oxide, a tyrosine phosphatase inhibitor, induced the formation of normal, stable focal adhesions similar to those on firm substrates. Conversely, treatment of cells on firm substrates with myosin inhibitors 2,3-butanedione monoxime or KT5926 caused the reduction of both vinculin and phosphotyrosine at adhesion sites. These results demonstrate the ability of cells to survey the mechanical properties of their surrounding environment and suggest the possible involvement of both protein tyrosine phosphorylation and myosin-generated cortical forces in this process. Such response to physical parameters likely represents an important mechanism of cellular interaction with the surrounding environment within a complex organism.
Role of calpain in skeletal-muscle protein degradation
Authors: Huang Jing , Forsberg Neil E.
Published: July 2002

Although protein degradation is enhanced in muscle-wasting conditions and limits the rate of muscle growth in domestic animals, the proteolytic system responsible for degrading myofibrillar proteins in skeletal muscle is not well defined. The goals of this study were to evaluate the roles of the calpains (calcium-activated cysteine proteases) in mediating muscle protein degradation and the extent to which these proteases participate in protein turnover in muscle. Two strategies to regulate intracellular calpain activities were developed: overexpression of dominant-negative m-calpain and overexpression of calpastatin inhibitory domain. To express these constructs, L8 myoblast cell lines were transfected with LacSwitch plasmids, which allowed for isopropyl β-
d
-thiogalactoside-dependent expression of the gene of interest. Inhibition of calpain stabilized fodrin, a well characterized calpain substrate. Under conditions of accelerated degradation (serum withdrawal), inhibition of m-calpain reduced protein degradation by 30%, whereas calpastatin inhibitory domain expression reduced degradation by 63%. Inhibition of calpain also stabilized nebulin. These observations indicate that calpains play key roles in the disassembly of sarcomeric proteins. Inhibition of calpain activity may have therapeutic value in treatment of muscle-wasting conditions and may enhance muscle growth in domestic animals.
Fire–diffuse–fire model of dynamics of intracellular calcium waves
Authors: Dawson Silvina Ponce , Keizer Joel , Pearson John E.
Published: July 2002

When Ca
2+
is released from internal stores in living cells, the resulting wave of increased concentration can travel without deformation (continuous propagation) or with burst-like behavior (saltatory propagation). We analyze the “fire–diffuse–fire” model in order to illuminate the differences between these two modes of propagation. We show that the Ca
2+
release wave in immature
Xenopus
oocytes and cardiac myocytes is saltatory, whereas the fertilization wave in the mature oocyte is continuous.
Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases
Authors: Park Byeong-Woo , O’Rourke Donald M. , Wang Qiang , Davis James G. , Post Andrew , Qian Xiaolan , Greene Mark I.
Published: July 2002

Conversion of a malignant phenotype into a more normal one can be accomplished either by down-regulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185
neu
. We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northern analysis, was expressed at higher levels in anti-p185
neu
-treated tumor cells but not in cells expressing internalization defective p185
neu
receptors. This cDNA fragment was identical in amino acid sequence to the recently cloned mouse Tat binding protein-1 (mTBP1), which has 98.4% homology to the HIV tat-binding protein-1 (TBP1). TBP1 mRNA levels were found to be elevated on inhibition of the oncogenic phenotype of transformed cells expressing erbB family receptors. TBP1 overexpression diminished cell proliferation, reduced the ability of the parental cells to form colonies
in vitro
, and almost completely inhibited transforming efficiency in athymic mice when stably expressed in human tumor cells containing erbB family receptors. Collectively, these results suggest that the attenuation of erbB receptor signaling seems to be associated with activation/induction or recovery of a functional tumor suppressor-like gene,
TBP1
. Disabling erbB tyrosine kinases by antibodies or by trans-inhibition represents an initial step in triggering a TBP1 pathway.
Biological clocks
Authors: Ishida Norio , Kaneko Maki , Allada Ravi
Published: July 2002

Circadian rhythms describe biological phenomena that
oscillate with an ≈24-hour cycle. These rhythms include blood
pressure, body temperature, hormone levels, the number of immune cells
in blood, and the sleep-wake cycle. In this paper, we will focus on
common genes between species that are responsible for determining the
circadian behavior, especially some transcription factors (i.e., switch
genes) that serve to regulate many circadian rhythm genes. The intent
of this summary is to introduce the common molecular mechanism of
biological clocks between flies and humans and then to describe the
research from three laboratories that was presented in the session.