bluuebunny/crossref_metadata_2025 huggingface dataset:
Monte Carlo operators for orbit-averaged Fokker–Planck equations
Authors: Eriksson L.-G. , Helander P.
Published: July 2002

Monte Carlo operators for the orbit-averaged Fokker–Planck equation describing collisions and wave–particle interaction are constructed. Special emphasis is put on ion-cyclotron-resonance heating of tokamaks, but the results are applicable to general quasilinear processes in arbitrary magnetic configurations in which particle motion is integrable. All effects of nonstandard orbit topology, such as large orbit widths, are fully taken into account. The Monte Carlo operators may be used for simulating, e.g., radio-frequency heating, wave-driven spatial diffusion, and alpha particle slowing down.
Langevin equation versus kinetic equation: Subdiffusive behavior of charged particles in a stochastic magnetic field
Authors: Balescu R. , Wang Hai-Da , Misguich J. H.
Published: July 2002

The running diffusion coefficient D(t) is evaluated for a system of charged particles undergoing the effect of a fluctuating magnetic field and of their mutual collisions. The latter coefficient can be expressed either in terms of the mean square displacement (MSD) of a test particle, or in terms of a correlation between a fluctuating distribution function and the magnetic field fluctuation. In the first case a stochastic differential equation of Langevin type for the position of a test particle must be solved; the second problem requires the determination of the distribution function from a kinetic equation. Using suitable simplifications, both problems are amenable to exact analytic solution. The conclusion is that the equivalence of the two approaches is by no means automatically guaranteed. A new type of object, the ‘‘hybrid kinetic equation’’ is constructed: it automatically ensures the equivalence with the Langevin results. The same conclusion holds for the generalized Fokker–Planck equation. The (Bhatnagar–Gross–Krook) (BGK) model for the collisions yields a completely wrong result. A linear approximation to the hybrid kinetic equation yields an inexact behavior, but represents an acceptable approximation in the strongly collisional limit.
Experimental study of two-dimensional electron vortex dynamics in an applied irrotational shear flow
Authors: Eggleston D. L.
Published: July 2002

An electron column in a modified Malmberg–Penning trap is used to study the behavior of a single two-dimensional vortex in an imposed irrotational shear flow. Phosphor screen images are presented, showing the dispersion of a vortex in a strong shear flow. The images show a variety of phenomena, including the fission of the original vortex, the emission, stretching, and entrainment of filamentary arms, and turbulent diffusion. The vortex lifetime is measured as a function of applied shear, with vortex strength independently adjustable. These data are compared to the predictions of a fluid theory, which correctly identifies the key dimensionless parameter (shear rate/vorticity) and its critical value. The experimental lifetime of a vortex in a strong shear is found to be the same as the dispersion time of a patch of zero vorticity. The lifetime of an unsheared vortex appears to be limited by a slow diffusion that gradually weakens the vortex.
Transition to turbulence in a crossed-field gap
Authors: Christenson P. J. , Lau Y. Y.
Published: July 2002

The transition from laminar to turbulent behavior of the electron sheath in a cross-field gap is examined for the regime B≳BH, where B is the external magnetic field and BH is the Hull cutoff value. An analytic expression is presented for the critical emitted current beyond which laminar solutions cease to exist. A one-dimensional particle code is used to corroborate the analytic theory. This code shows several interesting properties when the emitted current exceeds the critical value. Chief among them is the presence of a turbulent microsheath near the cathode surface. The electrostatic potential in the gap’s vacuum region is found to oscillate at a frequency that is quite insensitive to the emitted current and to the electrons’ emission velocity.
Rotating nonlinear magnetic islands in a tokamak plasma
Authors: Smolyakov A. I. , Hirose A. , Lazzaro E. , Re G. B. , Callen J. D.
Published: July 2002

The nonlinear dynamics of rotating low m (poloidal mode number) tearing modes in a tokamak with external resonant magnetic perturbations is examined. Nonlinear evolution equations for the island width and the toroidal rotation frequency are derived within the two-fluid magnetohydrodynamic model, taking into account the plasma rotation and neoclassical parallel viscosity. The nonlinear stability of magnetic islands interacting with a static external magnetic perturbation is considered, and the critical magnetic field for the appearance of a locked mode is determined. It is shown that the coupling of the perpendicular and longitudinal plasma flow due to the neoclassical plasma viscosity enhances the amplitude of the critical magnetic field compared to the value obtained in a slab approximation. The perpendicular plasma viscosity causes a finite phase shift between the applied external field and the magnetic island, and further increases the value of the critical magnetic field required to induce a magnetic island.
Analytical results on the breakdown of the convective amplifier model caused by space–time random fluctuations
Authors: Mounaix Philippe
Published: July 2002

The space and time behavior of backscattering instabilities is computed analytically in the strongly damped regime and in the presence of space–time random fluctuations. The fluctuations are described by a Gaussian process with exponentially decaying correlation function. The breakdown of the strongly damped model of the instability is obtained as a divergence of the average amplitude and intensity of the backscattered light [H. A. Rose and D. F. DuBois, Phys. Rev. Lett. 72, 2883 (1994)]. The length and time it takes for this divergence to occur is analytically computed.
Modeling ion interpenetration, stagnation, and thermalization in colliding plasmas
Authors: Jones Michael E. , Winske D. , Goldman S. R. , Kopp R. A. , Rogatchev V. G. , Bel’kov S. A. , Gasparyan P. D. , Dolgoleva G. V. , Zhidkov N. V. , Ivanov N. V. , Kochubej Yu. K. , Nasyrov G. F. , Pavlovskii V. A. , Smirnov V. V. , Romanov Yu. A.
Published: July 2002

Ion interpenetration, stagnation, and energization processes are studied in colliding laser-produced plasma configurations relevant to Trident [R. G. Watt, Rev. Sci. Instrum. 64, 1770 (1993)] experiments using four different numerical methods: one-dimensional Monte Carlo and Lagrangian multifluid codes, and one- and two-dimensional hybrid (particle ions, fluid electrons) and single-fluid Lagrangian codes. Results from the four methodologies are compared for plasmas generated with gold and deuterated polyethylene (CD2) targets. Overall, the various codes give similar results concerning the initial expansion of the plasmas and their collisional interaction, the degree of stagnation, stagnation time, and amount of ion thermalization for gold targets, while multispecies techniques indicate a much softer stagnation for CD2 plasmas than the single-fluid model. Variations in the results of the calculations due to somewhat different initializations and parameters, as well as to different physics in the codes, are discussed.
Beta limits for the N=1 mode in rotating-toroidal-resistive plasmas surrounded by a resistive wall
Authors: Betti R.
Published: July 2002

The stability analysis of a high-β toroidal tokamak plasma is carried out in the presence of toroidal flow, finite plasma resistivity, and a surrounding shell of finite electrical resistivity. The beta limits for the n=1 mode are set by the resistive-wall-tearing mode (RWTM), the ideal-wall-tearing mode (IWTM), and the ideal-plasma-resistive-wall mode (IPRWM). Slow plasma rotation suppresses the RWTM while the IPRWM is not directly affected by slow plasma flow. For small plasma resistivity, the IPRWM is stabilized by fast flow only. For large plasma resistivity, the IPRWM only exists in a plasma rotating faster than the typical tearing mode growth rate, and its instability threshold is a complicated function of the wall position and rotation frequency. Very fast rotation can destabilize the ideal kink through centrifugal effects. Furthermore, for b/a (wall radius/plasma radius) below a critical value, a stationary plasma is stable to the n=1 ideal kink and tearing mode for large values of β.
Forced magnetic field line reconnection in electron magnetohydrodynamics
Authors: Avinash K. , Bulanov S. V. , Esirkepov T. , Kaw P. , Pegoraro F. , Sasorov P. V. , Sen A.
Published: July 2002

The forced reconnection of magnetic field lines within the framework of electron magnetohydrodynamics (EMHD) has been investigated. A broad class of solutions that describe stationary reconnection have been found. The time evolution of the plasma and of the magnetic field when perturbations are imposed from the boundary of a high conductivity plasma slab are also studied. The initial magnetic field has a null surface. Following this discussion, the so-called Taylor’s problem for EMHD in which the perturbations cause a change in the topology of the magnetic field has been solved. The plasma and the magnetic field are seen to evolve with the time scale of the linear tearing mode. Their time evolution is described by exponential dependences. Analytic and numerical simulation results of the nonlinear regime of forced magnetic reconnection in EMHD are also presented. Finally, the above results are compared with a case where the reconnection is mediated by dissipative electron viscosity effects.
Magnetohydrodynamic stability in a levitated dipole
Authors: Garnier D. T. , Kesner J. , Mauel M. E.
Published: July 2002

Plasma confined by a magnetic dipole is stabilized, at low beta, by magnetic compressibility. The ideal magnetohydrodynamic (MHD) requirements for stability against interchange and high-n ballooning modes are derived at arbitrary beta for a fusion grade laboratory plasma confined by a levitated dipole. A high beta MHD equilibrium is found numerically with a pressure profile near marginal stability for interchange modes, a peak local beta of β∼10, and volume averaged beta of β̄∼0.5. This equilibrium is demonstrated to be ballooning stable on all field lines.
Neoclassical transport coefficients for general axisymmetric equilibria in the banana regime
Authors: Angioni C. , Sauter O.
Published: July 2002

Using the standard approach of neoclassical theory, a set of relatively simple kinetic equations has been obtained, suited for an implementation in a numerical code to compute a related set of distribution functions. The transport coefficients are then expressed by simple integrals of these functions and they can be easily computed numerically. The code CQL3D [R. W. Harvey and M. G. McCoy, in Proceedings of IAEA Technical Committee Meeting on Advances in Simulation and Modeling of Thermonuclear Plasmas, Montreal, 1992 (International Atomic Energy Agency, Vienna, 1993), pp. 489–526], which uses the full collision operator and considers the realistic axisymmetric configuration of the magnetic surfaces, has been modified to solve the bounce-averaged version of these equations. The coefficients have then been computed for a wide variety of equilibrium parameters, high-lighting interesting features of the influence of geometry at small aspect ratio. Differences with the most recent formulas for the ion neoclassical heat conductivity are pointed out. A set of formulas, which fit the code results, is obtained to easily evaluate all the neoclassical transport coefficients in the banana regime, at all aspect ratios, in general axisymmetric equilibria. This work extends to all the other transport coefficients, at least in the banana regime, the work of Sauter et al. [O. Sauter, C. Angioni, and Y. R. Lin-Liu, Phys. Plasmas 6, 2834 (1999)] which evaluates the neoclassical conductivity and all the bootstrap current coefficients. Formulas for arbitrary collisionality regime are proposed, obtained combining our results for the banana regime with the results of Hinton and Hazeltine [F. L. Hinton and R. D. Hazeltine, Rev. Mod. Phys. 48, 239 (1976)], adapted for small aspect ratio.
First observation of an extremely large-dipole infrared transition within the conduction band of a GaAs quantum well
Authors: West L. C. , Eglash S. J.
Published: July 2002

A new type of optical transition in GaAs quantum wells has been observed. The dipole occurs between two envelope states of the conduction-band electron wave function, and is called a quantum well envelope state transition (QWEST). The QWEST is observed by infrared absorption for two structures with 65-Å-thick- and 82-Å-thick wells. The transitions exhibit resonant energies of 152 and 121 meV respectively, full width at half-maximum linewidths as narrow as 10 meV at room temperature, and an oscillator strength of 12.2. The material is anticipated to have subpicosecond relaxation times and be ideal for low-power optical digital logic.
Nanometer lithography with the scanning tunneling microscope
Authors: Ringger M. , Hidber H. R. , Schlögl R. , Oelhafen P. , Güntherodt H.-J.
Published: July 2002

Nanometer structures have been produced with the scanning tunneling microscope. These structures have been identified by high resolution scanning electron microscopy. This effect seems to have a potential in high resolution microfabrication of semiconductor and superconductor devices.
Calculation of critical layer thickness versus lattice mismatch for GexSi1−x/Si strained-layer heterostructures
Authors: People R. , Bean J. C.
Published: July 2002

A calculation of the critical layer thickness hc for growth of GexSi1−x strained layers on Si substrates is presented for 0≤x≤1.0. The present results are obtained assuming misfit dislocation generation is determined solely by energy balance. This approach differs therefore from previous theories (e.g., Matthews et al.), in which the absence of mechanical equilibrium for grown-in threading dislocations determines the onset of the generation of interfacial misfit dislocations. It is assumed that interfacial misfit dislocations will be generated when the areal strain energy density of the film exceeds the energy density associated with the formation of a screw dislocation at a distance from the free surface equal to the film thickness h. For films thicker than this critical value, screw (and edge) dislocations will be generated at the film/substrate interface. Values obtained for the critical thickness versus lattice mismatch are in excellent agreement with measurements of hc for GexSi1−x strained layers on Si substrates.
1/f and random telegraph noise in silicon metal-oxide-semiconductor field-effect transistors
Authors: Uren M. J. , Day D. J. , Kirton M. J.
Published: July 2002

We demonstrate that deviations from 1/ f noise behavior found in submicron silicon metal-oxide-semiconductor field-effect transistors operating at room temperature are the direct result of the decomposition of the 1/ f spectrum into its constituent Lorentzian components. In the time domain, these devices produce random telegraph signals due to localized and discrete modulations of the channel resistance caused by individual carrier trapping events.
Guided-wave acousto-optic interaction in proton-exchanged Y-cut LiNbO3
Authors: Dawar A. L. , Al-Shukri S. M. , De La Rue R. M.
Published: July 2002

We report for the first time results for acousto-optic interaction in proton-exchange waveguides in Y-LiNbO3. The value of acousto-optic diffraction efficiency was as high as 72% for an electrical input power of 540 mW at 425 MHz.
On the relative importance of physical and chemical sputtering during ion-enhanced etching of silicon by XeF2
Authors: Houle F. A.
Published: July 2002

Product translational energy distributions have been used in previous studies as a diagnostic of surface reaction enhancement mechanisms under ion bombardment. Haring and co-workers [R. A. Haring, A. Haring, F. W. Saris, and A. E. de Vries, Appl. Phys. Lett. 41, 174 (1982)] have taken an E−2 dependence for SiFx species desorbing during ion-enhanced etching of silicon as evidence for the importance of physical sputtering. In this work, the translational energy distribution of SiF4 desorbing from the surface of silicon during spontaneous etching by XeF2 has been obtained from modulated beam measurements. The distribution deviates markedly from a thermal distribution at the surface temperature and exhibits an E−2 dependence at high energy. Observation of this energy dependence both with and without ions suggests that translational energy distributions may not provide a unique signature for chemical and physical sputtering.
p on n ion-implanted junctions in liquid phase epitaxy HgCdTe layers on CdTe substrates
Authors: Bubulac L. O. , Lo D. S. , Tennant W. E. , Edwall D. D. , Chen J. C. , Ratusnik J. , Robinson J. C. , Bostrup G.
Published: July 2002

The first demonstrated achievement of p on n-type activated junctions in HgCdTe material by arsenic ion implantation is reported. The junctions were formed by treating the implant as a finite diffusion source in the post-implant anneals. The materials employed for this study were n-type indium impurity-doped liquid phase epitaxy HgCdTe grown on CdTe. Arsenic was selected as the candidate acceptor impurity since it activated during post-implanted anneals in Hg vapor. The arsenic concentration profile determined by secondary ion mass spectroscopy showed that during post-implant anneal a complex diffusion mechanism redistributes the arsenic. The activation efficiency appears to be mechanism dependent. In the junction region the implant activation efficiency is about 50%. Junction depth can be controlled by varying arsenic diffusion and background carrier concentration. Junction depths determined by the electron beam induced current technique were consistent with the differential Hall electrical profiles. A p on n junction is shown with excellent rectification characteristics and high breakdown voltage (sharp at 2.5 V and 77 °C). This was obtained from a liquid phase epitaxy Hg1−xCdxTe, with a compositional factor of x=0.23.
Tribological and electrical properties of metal-containing hydrogenated carbon films
Authors: Dimigen H. , Hübsch H. , Memming R.
Published: July 2002

The formation of metal-containing amorphous hydrogenated carbon films (a-C:H) in a reactive sputtering process is reported. The layers were prepared at room temperature using various metals of different concentrations. According to tribological measurements the layers exhibit small friction values and an extremely low abrasive wear rate. The electrical conductivity depends on the metal concentration and could be varied over many orders of magnitude.
Mechanisms of buried oxide formation by ion implantation
Authors: White Alice E. , Short K. T. , Batstone J. L. , Jacobson D. C. , Poate J. M. , West K. W.
Published: July 2002

We have studied the process of buried oxide formation as a function of implantation and annealing conditions. Concentrating on substoichiometric implants (<1×1018 O/cm2), we varied the implantation energies from 100 keV to 1 MeV. Some apparent precipitation of SiO2 similar to that observed in Czochralski-grown silicon occurs on implantation. This means that formation of the buried oxide layer and perfection of the overlying crystalline Si layer depend more strongly on the substrate temperature during the implant than on the annealing temperature.
Observation of optical Stark effect in InGaAs/InP multiple quantum wells
Authors: Tai K. , Hegarty J. , Tsang W. T.
Published: July 2002

We report an experimental observation of a blue shift in the n=1 heavy-hole exciton line of In0.53Ga0.47As/InP multiple quantum wells resulting from a picosecond photoexcitation in the transparent spectral region. The temporal response of this shift follows the excitation and it is attributed to the optical Stark effect. The shift was measured to be 0.19 meV for an incident light with a photon energy 20 meV below the exciton peak and with a 10-MW/cm2 intensity.
Temperature dependence of electron mobility and peak velocity in compensated GaAs
Authors: Xu Jingming , Shur Michael
Published: July 2002

The temperature dependences of electron mobility and peak velocity in compensated GaAs have been calculated by using a Monte Carlo technique. It is found that both mobility and peak velocity are substantially reduced and less temperature dependent in compensated material because of an increased impurity scattering.
Selective deposition of diamond crystals by chemical vapor deposition using a tungsten-filament method
Authors: Hirabayashi K. , Taniguchi Y. , Takamatsu O. , Ikeda T. , Ikoma K. , Iwasaki-Kurihara N.
Published: July 2002

Selective deposition of polycrystalline and single-crystal diamonds has been achieved on a silicon wafer by chemical vapor deposition from CH4 and H2 gases using a hot-filament method. The nucleation of diamonds occurs selectively at the sites fabricated by successive roughening and patterned etching of wafers.
Chaos in learning a simple two-person game
Authors: Sato Yuzuru , Akiyama Eizo , Farmer J. Doyne
Published: July 2002

We investigate the problem of learning to play the game of rock–paper–scissors. Each player attempts to improve her/his average score by adjusting the frequency of the three possible responses, using reinforcement learning. For the zero sum game the learning process displays Hamiltonian chaos. Thus, the learning trajectory can be simple or complex, depending on initial conditions. We also investigate the non-zero sum case and show that it can give rise to chaotic transients. This is, to our knowledge, the first demonstration of Hamiltonian chaos in learning a basic two-person game, extending earlier findings of chaotic attractors in dissipative systems. As we argue here, chaos provides an important self-consistency condition for determining when players will learn to behave as though they were fully rational. That chaos can occur in learning a simple game indicates one should use caution in assuming real people will learn to play a game according to a Nash equilibrium strategy.
Identification of a
Plasmodium falciparum
intercellular adhesion molecule-1 binding domain: A parasite adhesion trait implicated in cerebral malaria
Authors: Smith Joseph D. , Craig Alister G. , Kriek Neline , Hudson-Taylor Diana , Kyes Sue , Fagen Toby , Pinches Robert , Baruch Dror I. , Newbold Chris I. , Miller Louis H.
Published: July 2002

Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cerebral malaria. The only parasite adhesion trait linked to cerebral sequestration is binding to intercellular adhesion molecule-1 (ICAM-1). In this report, we show that
Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from the A4tres parasite. Using heterologous expression in mammalian cells, the minimal ICAM-1 binding domain was a complex domain consisting of the second Duffy binding-like (DBL) domain and the C2 domain. Constructs that contained either domain alone did not bind ICAM-1. Based on phylogenetic criteria, there are five distinct PfEMP1 DBL types designated α, β, γ, δ, and ɛ. The DBL domain from the A4tres that binds ICAM-1 is DBLβ type. A PfEMP1 cloned from a distinct ICAM-1 binding variant, the A4 parasite, contains a DBLβ domain and a C2 domain in tandem arrangement similar to the A4tres PfEMP1. Anti-PfEMP1 antisera implicate the DBLβ domain from A4var PfEMP1 in ICAM-1 adhesion. The identification of a
P. falciparum
ICAM-1 binding domain may clarify mechanisms responsible for the pathogenesis of cerebral malaria and lead to interventions or vaccines that reduce malarial disease.
Crystal structure of the zymogen form of the group A
Streptococcus
virulence factor SpeB: An integrin-binding cysteine protease
Authors: Kagawa Todd F. , Cooney Jakki C. , Baker Heather M. , McSweeney Sean , Liu Mengyao , Gubba Siddeswar , Musser James M. , Baker Edward N.
Published: July 2002

Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors. We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen
Streptococcus pyogenes
and participates in invasive disease episodes, including necrotizing fasciitis. The structure, determined for the 40-kDa precursor form of SpeB at 1.6-Å resolution, reveals that the protein is a distant homologue of the papain superfamily that includes the mammalian cathepsins B, K, L, and S. Despite negligible sequence identity, the protease portion has the canonical papain fold, albeit with major loop insertions and deletions. The catalytic site differs from most other cysteine proteases in that it lacks the Asn residue of the Cys-His-Asn triad. The prosegment has a unique fold and inactivation mechanism that involves displacement of the catalytically essential His residue by a loop inserted into the active site. The structure also reveals the surface location of an integrin-binding Arg-Gly-Asp (RGD) motif that is a feature unique to SpeB among cysteine proteases and is linked to the pathogenesis of the most invasive strains of
S. pyogenes
.
Light affects cAMP signaling and cell movement activity in
Dictyostelium discoideum
Authors: Miura Kota , Siegert Florian
Published: July 2002

The multicellular, slug stage of the slime mould
Dictyostelium discoideum
lacks specific sensory cells and organs but can nevertheless respond in a very sensitive manner to external stimuli such as temperature and light. Within the migrating slug, the behavior of up to 100,000 individual amoebae is coordinated by cAMP mediated cell–cell signaling and chemotaxis. We report here the striking result that light directly modulates the cAMP cell–cell signaling system. Light-induced secretion of cAMP from the slug tips decreased the period length of optical density waves and speeded up cell movement. A local effect of light on cAMP release within the slug tip could modulate cell movement within the slug and thus control its phototactic turning and orientation toward a light source.
Clustering of connexin 43–enhanced green fluorescent protein gap junction channels and functional coupling in living cells
Authors: Bukauskas Feliksas F. , Jordan Karen , Bukauskiene Angele , Bennett Michael V. L. , Lampe Paul D. , Laird Dale W. , Verselis Vytas K.
Published: July 2002

Communication-incompetent cell lines were transfected with connexin
(Cx) 43 fused with enhanced green fluorescent protein (EGFP) to examine
the relation between Cx distribution determined by fluorescence
microscopy and electrical coupling measured at single-channel
resolution in living cell pairs. Cx43–EGFP channel properties were
like those of wild-type Cx43 except for reduced sensitivity to
transjunctional voltage. Cx43–EGFP clustered into plaques at locations
of cell–cell contact. Coupling was always absent in the absence of
plaques and even in the presence of small plaques. Plaques exceeding
several hundred channels always conferred coupling, but only a small
fraction of channels were functional. These data indicate that
clustering may be a requirement for opening of gap junction channels.
Phylogeny of genes for secretion NTPases: Identification of the widespread
tadA
subfamily and development of a diagnostic key for gene classification
Authors: Planet Paul J. , Kachlany Scott C. , DeSalle Rob , Figurski David H.
Published: July 2002

Macromolecular transport systems in bacteria currently are
classified by function and sequence comparisons into five basic types.
In this classification system, type II and type IV secretion systems
both possess members of a superfamily of genes for putative NTP
hydrolase (NTPase) proteins that are strikingly similar in structure,
function, and sequence. These include VirB11, TrbB, TraG, GspE, PilB,
PilT, and ComG1. The predicted protein product of
tadA
,
a recently discovered gene required for tenacious adherence of
Actinobacillus actinomycetemcomitans
, also has
significant sequence similarity to members of this superfamily and to
several unclassified and uncharacterized gene products of both Archaea
and Bacteria. To understand the relationship of
tadA
and
tadA
-like genes to those encoding the putative NTPases
of type II/IV secretion, we used a phylogenetic approach to obtain a
genealogy of 148 NTPase genes and reconstruct a scenario of gene
superfamily evolution. In this phylogeny, clear distinctions can be
made between type II and type IV families and their constituent
subfamilies. In addition, the subgroup containing
tadA
constitutes a novel and extremely widespread subfamily of the family
encompassing all putative NTPases of type IV secretion systems. We
report diagnostic amino acid residue positions for each major
monophyletic family and subfamily in the phylogenetic tree, and we
propose an easy method for precisely classifying and naming putative
NTPase genes based on phylogeny. This molecular key-based method can be
applied to other gene superfamilies and represents a valuable tool for
genome analysis.
Testicular FasL is expressed by sperm cells
Authors: D'Alessio Alessio , Riccioli Anna , Lauretti Paola , Padula Fabrizio , Muciaccia Barbara , De Cesaris Paola , Filippini Antonio , Nagata Shigekazu , Ziparo Elio
Published: July 2002

The testis is the main source of Fas ligand (FasL) mRNA in rodents; it is generally believed that this molecule, expressed on bordering somatic Sertoli cells, bestows an immune-privileged status in the testis by eliminating infiltrating inflammatory Fas-bearing leukocytes. Our results demonstrate that the attribution of testicular expression of FasL to Sertoli cells is erroneous and that FasL transcription instead occurs in meiotic and postmeiotic germ cells, whereas the protein is only displayed on mature spermatozoa. These findings point to a significant role of the Fas system in the biology of mammalian reproduction.
Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial
Authors: Gilewski Teresa , Ragupathi Govindaswami , Bhuta Sonal , Williams Lawrence J. , Musselli Cristina , Zhang Xu-Fang , Bencsath Kalman P. , Panageas Katherine S. , Chin Jeanette , Hudis Clifford A. , Norton Larry , Houghton Alan N. , Livingston Philip O. , Danishefsky Samuel J.
Published: July 2002

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.
Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors
Authors: Reyes T. M. , Lewis K. , Perrin M. H. , Kunitake K. S. , Vaughan J. , Arias C. A. , Hogenesch J. B. , Gulyas J. , Rivier J. , Vale W. W. , Sawchenko P. E.
Published: July 2002

Here we describe the cloning and initial characterization of a
previously unidentified CRF-related neuropeptide, urocortin II (Ucn
II). Searches of the public human genome database identified a region
with significant sequence homology to the CRF neuropeptide family. By
using homologous primers deduced from the human sequence, a mouse cDNA
was isolated from whole brain poly(A)
+
RNA that encodes a
predicted 38-aa peptide, structurally related to the other known
mammalian family members, CRF and Ucn. Ucn II binds selectively to the
type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1.
Transcripts encoding Ucn II are expressed in discrete regions of the
rodent central nervous system, including stress-related cell groups in
the hypothalamus (paraventricular and arcuate nuclei) and brainstem
(locus coeruleus). Central administration of 1–10 μg of peptide
elicits activational responses (Fos induction) preferentially within a
core circuitry subserving autonomic and neuroendocrine regulation, but
whose overall pattern does not broadly mimic the CRF-R2 distribution.
Behaviorally, central Ucn II attenuates nighttime feeding, with a time
course distinct from that seen in response to CRF. In contrast to CRF,
however, central Ucn II failed to increase gross motor activity. These
findings identify Ucn II as a new member of the CRF family of
neuropeptides, which is expressed centrally and binds selectively to
CRF-R2. Initial functional studies are consistent with Ucn II
involvement in central autonomic and appetitive control, but not in
generalized behavioral activation.
Mapping the intrinsic curvature and flexibility along the DNA chain
Authors: Zuccheri Giampaolo , Scipioni Anita , Cavaliere Valeria , Gargiulo Giuseppe , De Santis Pasquale , Samorì Bruno
Published: July 2002

The energy of DNA deformation plays a crucial and active role in
its packaging and its function in the cell. Considerable effort has
gone into developing methodologies capable of evaluating the local
sequence-directed curvature and flexibility of a DNA chain. These
studies thus far have focused on DNA constructs expressly tailored
either with anomalous flexibility or curvature tracts. Here we
demonstrate that these two structural properties can be mapped also
along the chain of a “natural” DNA with any sequence on the basis
of its scanning force microscope (SFM) images. To know the orientation
of the sequence of the investigated DNA molecules in their SFM images,
we prepared a palindromic dimer of the long DNA molecule under study.
The palindromic symmetry also acted as an internal gauge of the
statistical significance of the analysis carried out on the SFM images
of the dimer molecules. It was found that although the curvature
modulus is not efficient in separating static and dynamic contributions
to the curvature of the population of molecules, the curvature taken
with its direction (its sign in two dimensions) permits the direct
separation of the intrinsic curvature from the flexibility
contributions. The sequence-dependent flexibility seems to vary
monotonically with the chain's intrinsic curvature; the chain rigidity
was found to modulate as its local thermodynamic stability and does not
correlate with the dinucleotide chain rigidities evaluation made from
x-ray data by other authors.
Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development
Authors: Sekiguchi JoAnn , Ferguson David O. , Chen Hua Tang , Yang Eva Mary , Earle John , Frank Karen , Whitlow Scott , Gu Yansong , Xu Yang , Nussenzweig André , Alt Frederick W.
Published: July 2002

DNA ligase IV (Lig4) and the DNA-dependent protein kinase
(DNA-PK) function in nonhomologous end joining (NHEJ). However,
although Lig4 deficiency causes late embryonic lethality, deficiency in
DNA-PK subunits (Ku70, Ku80, and DNA-PKcs) does not. Here we
demonstrate that, similar to p53 deficiency,
ataxia-telangiectasia-mutated (ATM) gene deficiency rescues the
embryonic lethality and neuronal apoptosis, but not impaired
lymphocyte development, associated with Lig4 deficiency. However, in
contrast to p53 deficiency, ATM deficiency enhances deleterious effects
of Lig4 deficiency on growth potential of embryonic fibroblasts (MEFs)
and genomic instability in both MEFs and cultured progenitor
lymphocytes, demonstrating significant differences in the
interplay of p53 vs. ATM with respect to NHEJ. Finally, in dramatic
contrast to effects on Lig4 deficiency, ATM deficiency causes early
embryonic lethality in Ku- or DNA-PKcs-deficient mice, providing
evidence for an NHEJ-independent role for the DNA-PK holoenzyme.
An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels
Authors: Diamonti A. John , Guy Pamela M. , Ivanof Caryn , Wong Karen , Sweeney Colleen , Carraway Kermit L.
Published: July 2002

Despite numerous recent advances in our understanding of the molecular mechanisms underlying receptor tyrosine kinase down-regulation and degradation in response to growth factor binding, relatively little is known about ligand-independent receptor tyrosine kinase degradation mechanisms. In a screen for proteins that might regulate the trafficking or localization of the ErbB3 receptor, we have identified a tripartite or RBCC (RING, B-box, coiled–coil) protein that interacts with the cytoplasmic tail of the receptor in an activation-independent manner. We have named this protein Nrdp1 for neuregulin receptor degradation protein-1. Northern blotting reveals ubiquitous distribution of Nrdp1 in human adult tissues, but message is particularly prominent in heart, brain, and skeletal muscle. Nrdp1 interacts specifically with the neuregulin receptors ErbB3 and ErbB4 and not with epidermal growth factor receptor or ErbB2. When coexpressed in COS7 cells, Nrdp1 mediates the redistribution of ErbB3 from the cell surface to intracellular compartments and induces the suppression of ErbB3 and ErbB4 receptor levels but not epidermal growth factor receptor or ErbB2 levels. A putative dominant-negative form of Nrdp1 potentiates neuregulin-stimulated Erk1/2 activity in transfected MCF7 breast tumor cells. Our observations suggest that Nrdp1 may act to regulate steady-state cell surface neuregulin receptor levels, thereby influencing the efficiency of neuregulin signaling.
Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen
Authors: Cunningham Kristina , Lacy D. Borden , Mogridge Jeremy , Collier R. John
Published: July 2002

Assembly of anthrax toxin complexes at the mammalian cell surface involves competitive binding of the edema factor (EF) and lethal factor (LF) to heptameric oligomers and lower order intermediates of PA
63
, the activated carboxyl-terminal 63-kDa fragment of protective antigen (PA). We used sequence differences between PA
63
and homologous PA-like proteins to delineate a region within domain 1′ of PA that may represent the binding site for these ligands. Substitution of alanine for any of seven residues in or near this region (R178, K197, R200, P205, I207, I210, and K214) strongly inhibited ligand binding. Selected mutations from this set were introduced into two oligomerization-deficient PA mutants, and the mutants were used in various combinations to map the single ligand site within dimeric PA
63
. The site was found to span the interface between two adjacent subunits, explaining the dependence of ligand binding on PA oligomerization. The locations of residues comprising the site suggest that a single ligand molecule sterically occludes two adjacent sites, consistent with the finding that the PA
63
heptamer binds a maximum of three ligand molecules. These results elucidate the process by which the components of anthrax toxin, and perhaps other binary bacterial toxins, assemble into toxic complexes.
Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the
telomerase reverse transcriptase
promoter during differentiation of HL60 cells
Authors: Xu Dawei , Popov Nikita , Hou Mi , Wang Qian , Björkholm Magnus , Gruber Astrid , Menkel Annette R. , Henriksson Marie
Published: July 2002

Recent evidence suggests that the Myc and Mad1 proteins are
implicated in the regulation of the gene encoding the human telomerase
reverse transcriptase (hTERT), the catalytic subunit of telomerase. We
have analyzed the
in vivo
interaction between
endogenous c-Myc and Mad1 proteins and the
hTERT
promoter in HL60 cells with the use of the
chromatin immunoprecipitation assay. The E-boxes at the
hTERT
proximal promoter were occupied
in
vivo
by c-Myc in exponentially proliferating HL60 cells but not
in cells induced to differentiate by DMSO. In contrast, Mad1 protein
was induced and bound to the
hTERT
promoter in
differentiated HL60 cells. Concomitantly, the acetylation of the
histones at the promoter was significantly reduced. These data suggest
that the reciprocal E-box occupancy by c-Myc and Mad1 is responsible
for activation and repression of the
hTERT
gene in
proliferating and differentiated HL60 cells, respectively. Furthermore,
the histone deacetylase inhibitor trichostatin A inhibited
deacetylation of histones at the
hTERT
promoter and
attenuated the repression of
hTERT
transcription during
HL60 cell differentiation. In addition, trichostatin A treatment
activated
hTERT
transcription in resting human
lymphocytes and fibroblasts. Taken together, these results indicate
that acetylation/deacetylation of histones is operative in the
regulation of
hTERT
expression.
Dwarfism and early death in mice lacking C-type natriuretic peptide
Authors: Chusho Hideki , Tamura Naohisa , Ogawa Yoshihiro , Yasoda Akihiro , Suda Michio , Miyazawa Takashi , Nakamura Kenji , Nakao Kazuki , Kurihara Tatsuya , Komatsu Yasato , Itoh Hiroshi , Tanaka Kiyoshi , Saito Yoshihiko , Katsuki Motoya , Nakao Kazuwa
Published: July 2002

Longitudinal bone growth is determined by endochondral ossification
that occurs as chondrocytes in the cartilaginous growth plate undergo
proliferation, hypertrophy, cell death, and osteoblastic replacement.
The natriuretic peptide family consists of three structurally related
endogenous ligands, atrial, brain, and C-type natriuretic
peptides (ANP, BNP, and CNP), and is thought to be involved in a
variety of homeostatic processes. To investigate the physiological
significance of CNP
in vivo
, we generated mice with
targeted disruption of CNP (
Nppc
−/−
mice).
The
Nppc
−/−
mice show severe dwarfism as a
result of impaired endochondral ossification. They are all viable
perinatally, but less than half can survive during postnatal
development. The skeletal phenotypes are histologically similar to
those seen in patients with achondroplasia, the most common genetic
form of human dwarfism. Targeted expression of CNP in the growth plate
chondrocytes can rescue the skeletal defect of
Nppc
−/−
mice and allow their prolonged
survival. This study demonstrates that CNP acts locally as a positive
regulator of endochondral ossification
in vivo
and
suggests its pathophysiological and therapeutic implication in some
forms of skeletal dysplasia.
The combined absence of NF-κB1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells
Authors: Pohl Thomas , Gugasyan Raffi , Grumont Raelene J. , Strasser Andreas , Metcalf Donald , Tarlinton David , Sha William , Baltimore David , Gerondakis Steve
Published: July 2002

Transcription factors NF-κB1 and c-Rel, individually dispensable during embryogenesis, serve similar, yet distinct, roles in the function of mature hemopoietic cells. Redundancy among Rel/NF-κB family members prompted an examination of the combined roles of c-Rel and NF-κB1 by using mice that lack both proteins. Embryonic development and the maturation of hemopoietic progenitors were unaffected innfkb1−/−c-rel−/−mice. Peripheral T cell populations developed normally, but follicular, marginal zone, and CD5+peritoneal B cell populations all were reduced. In culture, a failure of mitogen-stimulatednfkb1−/−c-rel−/−B cells to proliferate was caused by a cell cycle defect in early G1that prevented growth.In vivo, defects in humoral immunity and splenic architecture seen innfkb1−/−andc-rel−/−mice were exacerbated in the double mutant mice. These findings demonstrate that in the B lineage overlapping roles for NF-κB1 and c-Rel appear to be restricted to regulating the activation and function of mature cells.
Comparative assessment of virulence of recombinant vaccinia viruses expressing IL-2 and IL-15 in immunodeficient mice
Authors: Perera Liyanage P. , Goldman Carolyn K. , Waldmann Thomas A.
Published: July 2002

IL-2 and -15 belong to the four α-helix bundle family of cytokines and display a spectrum of overlapping immune functions because of shared signal transducing receptor components of the IL-2 receptor complex. However, recent evidence suggests a nonredundant unique role for IL-15 in the establishment and perhaps maintenance of peripheral natural killer (NK) cell populationsin vivo. To explore the contribution of locally released IL-15 on peripheral NK-cell-mediated innate immune responses, we generated a recombinant vaccinia virus that expresses IL-15 and evaluated the course of vaccinial disease in athymic nude mice. Coexpression of IL-15 resulted in the attenuation of virulence of vaccinia virus, and mice inoculated with 105plaque-forming units or less resolved the infection successfully. In contrast, mice inoculated with a similar dose of the control vaccinia virus failed to eliminate the virus and died of generalized vaccinial disease. Enhanced expression of IL-12 and IFN-γ as well as induction of chemokines were evident in the mice inoculated with IL-15-expressing vaccinia virus in addition to an increase in NK cells in the spleen. However, in this model system, the degree of attenuation in viral virulence attained with coexpression of IL-15 was much less than that achieved with coexpression of IL-2, suggesting that the peripheral NK-cell-mediated events are more responsive to IL-2 than to IL-15.
A ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO)-like protein from
Chlorobium tepidum
that is involved with sulfur metabolism and the response to oxidative stress
Authors: Hanson Thomas E. , Tabita F. Robert
Published: July 2002

A gene encoding a product with substantial similarity to
ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) was
identified in the preliminary genome sequence of the green sulfur
bacterium
Chlorobium tepidum
. A highly similar gene was
subsequently isolated and sequenced from
Chlorobium
limicola
f.sp.
thiosulfatophilum
strain
Tassajara. Analysis of these amino acid sequences indicated that they
lacked several conserved RubisCO active site residues. The
Chlorobium
RubisCO-like proteins are most closely
related to deduced sequences in
Bacillus subtilis
and
Archaeoglobus fulgidus
, which also lack some typical
RubisCO active site residues. When the
C. tepidum
gene
encoding the RubisCO-like protein was disrupted, the resulting mutant
strain displayed a pleiotropic phenotype with defects in photopigment
content, photoautotrophic growth and carbon fixation rates, and sulfur
metabolism. Most important, the mutant strain showed substantially
enhanced accumulation of two oxidative stress proteins. These results
indicated that the
C. tepidum
RubisCO-like protein might
be involved in oxidative stress responses and/or sulfur metabolism.
This protein might be an evolutional link to
bona fide
RubisCO and could serve as an important tool to analyze how the RubisCO
active site developed.