bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytic theory for the selection of a symmetric Saffman–Taylor finger in a Hele–Shaw cell
Authors: Tanveer S.
Published: July 2002

An analytic theory is presented for the selection mechanism of a symmetric finger with a discrete set of possible width from a continuum of nonsymmetric Saffman–Taylor finger solutions of arbitrary width. Both linear and nonlinear analyses have been carried out and in almost all cases, it is shown analytically that nonsymmetric solutions do not exist for nonzero surface tension if the finger boundary is assumed to be smooth. In the other cases, numerical calculations appear to support the same conclusions. In the asymptotic range, the predicted set of countably infinite possible finger widths according to nonlinear analysis agree with the previous analytical results of Combescot et al. [Phys. Rev. Lett. 56, 2036 (1986)] for a finger assumed to be symmetric about the channel centerline. The predicted coefficient of the power law dependence of finger width on surface tension for the first few of these solutions, i.e., on the branches first calculated by Mclean–Saffman [J. Fluid Mech. 102, 455 (1980)], Romero (Ph.D. thesis, California Institute of Technology, 1982) and Vanden-Broeck [Phys. Fluids 26, 2033 (1983)], are in agreement with Tanveer’s [Phys. Fluids 30, 651 (1987)] estimate of this coefficient based on numerical calculations of bubbles. It is also shown that the nonlinear analysis has the same qualitative features as the linear analysis and, in the asymptotic range, the agreement is close.
Measurement of a potential barrier created by electron cyclotron resonance heating
Authors: Chang C. P. , Lieberman M. A. , Meuth H. , Lichtenberg A. J.
Published: July 2002

An electrostatic potential well and mirror-trapped hot electrons are created by high power (250 kW), short pulse (3 μsec) electron cyclotron resonance heating (ECRH) of a plasma in one magnetic mirror cell of a multiple mirror experiment. The creation and subsequent decay of the potential well is measured by an electron beam, time-of-flight diagnostic. Typically, the barrier rises to −40 V just after ECRH and decays within 100 μsec. A numerical model of the barrier evolution is developed, and the numerical results along with the experimental observations are presented. Both the numerical results and the experimental observations indicate a correlation between the degree of heating (diamagnetic loop voltage output) and the longevity of the barrier. It is shown that the decay of the barrier is determined mainly by the hot-electron escape rate and the hot-electron-neutral ionization rate, rather than by trapping of the passing ions.
Experimental studies of divertor stabilization in an axisymmetric tandem mirror
Authors: Casey J. A. , Lane B. G. , Irby J. H. , Brau K. L. , Golovato S. N. , Guss W. C. , Kesner J. , Post R. S. , Sevillano E. , Zielinski J.
Published: July 2002

A divertor coil set has been installed on the Tara tandem mirror [Nucl. Fusion 22, 549 (1982); Plasma Physics and Controlled Nuclear Fusion Research 1984 (IAEA, Vienna, 1985), Vol. 2, p. 285] for stabilization of m=1 flutelike modes. The effectiveness of divertor stabilization is discussed in experiments where m=1 modes are driven to instability by plug electron cyclotron heating (ECH) in an ion cyclotron heated (ICH) plasma. The instability onset is characterized by thresholds in ECH power, fueling rate, ICH power, and mapping radius of the divertor null. In general, the stability is enhanced by mapping the null radially inwards into the plasma. The interdependence of these parameters and their effect on equilibrium profiles and stability boundaries are discussed.
Does fully developed turbulence exist? Reynolds number independence versus asymptotic covariance
Authors: Barenblatt G. I. , Goldenfeld Nigel
Published: July 2002

By analogy with recent arguments concerning the mean velocity profile of wall-bounded turbulent shear flows, we suggest that there may exist corrections to the 2/3 law of Kolmogorov, which are proportional to (ln Re)−1 at large Re. Such corrections to K41 are the only ones permitted if one insists that the functional form of statistical averages at large Re be invariant under a natural redefinition of Re. The family of curves of the observed longitudinal structure function DLL(r,Re) for different values of Re is bounded by an envelope. In one generic scenario, close to the envelope, DLL(r,Re) is of the form assumed by Kolmogorov, with corrections of O[(ln Re)−2]. In an alternative generic scenario, both the Kolmogorov constant CK and corrections to Kolmogorov’s linear relation for the third-order structure function DLLL(r) are proportional to (ln Re)−1. Recent experimental data of Praskovsky and Oncley appear to show a definite dependence of CK on Re, which, if confirmed, would be consistent with the arguments given here.
Structures and structure functions in the inertial range of turbulence
Authors: Boratav Oluş N. , Pelz Richard B.
Published: July 2002

The deviations from the Kolmogorov 1941 laws of inertial range of turbulence are investigated using the results from the direct numerical simulations of an unforced flow starting from a high-symmetry initial condition by Kida [J. Phys. Soc. Jpn. 54, 2132 (1985)]. The resolution is 3003 points (12003 with symmetries, maximum wavenumber 400 after dealiasing), and the Taylor scale Reynolds number is in the order of 100. The scaling exponents of the pth order longitudinal and lateral structure function (for p between 2 and 16) are computed using different methods with particular focus on a recent method by Benzi and collaborators [Phys. Rev. E 48, R29 (1993); Europhys. Lett. 32, 709 (1995)]. Both longitudinal and lateral scaling exponents deviate considerably from Kolmogorov 1941 (K-41) scaling laws, the lateral deviating much more than the longitudinal. A systematic methodology (strain–enstrophy state) is developed to relate the K-41 deviations to different structures in the field. Enstrophy-dominated structures are found to contribute mainly to the deviations in lateral direction whereas the strain-dominated structures to longitudinal direction, albeit in an imbalanced proportion, the lateral deviations being much stronger. Structures whose enstrophy and strain are comparable in magnitude contribute to deviations in both directions. Results are compared to several intermittency models and experiments. Special focus is given to the recent She–Lévêque model [Phys. Rev. Lett. 72, 336 (1994)] whose predictions gave very good agreement if compared to the longitudinal exponents. The model is rewritten for a family of free parameters, giving predictions as good as the original one. The lateral scaling exponents disagree with both the She–Lévêque model and the experimental results (from longitudinal velocity measurements) suggesting that the dominant contribution to intermittency can only be detected from the lateral structure function measurements.
Convection velocities in a turbulent boundary layer
Authors: Krogstad P.-Å. , Kaspersen J. H. , Rimestad S.
Published: July 2002

The convection velocities of ejections, sweeps, and shear layers have been studied in a turbulent boundary layer at Reθ=1409 by means of two-point correlations. Except in the buffer layer, where the convection velocities are reasonably constant, considerable variations in Uc are observed, both with respect to the distance from the wall and the scale of the event. The largest-scale motions (of the order of the boundary layer thickness) are convected at velocities close to the local mean. However, the velocities drop significantly as the scales are reduced for all types of events studied. Hence, the concept of a unique structure convection velocity does not appear to be very useful, since it must depend on the state of evolution of the structure. The propagation velocity also appears to be different for different parts of the event. It is found that for all scales and positions, the convection velocity for ejections is distinctly lower than that for sweeps, suggesting that the mechanisms responsible for the two types of events are quite different.
Shape and stability of doubly connected axisymmetric free surfaces in a cylindrical container
Authors: Slobozhanin Lev A. , Alexander J. Iwan D. , Fedoseyev Alexandre I.
Published: July 2002

The equilibrium and stability of a liquid that partially fills a cylindrical container with planar ends are examined. It is assumed that the free surface is axisymmetric and does not cross the symmetry axis of the container. Particular attention is given to the case where gravity is parallel to the cylinder’s axis, and where the free surface has one contact line on the lateral cylindrical wall and the other on one of the planar ends. The equilibrium configuration of such a surface is determined by the wetting angle, α, the Bond number, B, and the relative volume, V, of the annular region bounded by the free surface and the solid container. Shapes of stable and critical surfaces have been analyzed, and the stability regions for arbitrary Bond numbers have been obtained in the α–V plane. The shape and stability problems for a zero gravity configuration with both contact lines on the lateral wall of the cylinder are also studied. In addition, the stability of a free surface with at least one contact line coinciding with the edge formed by the lateral wall and a planar end is discussed.
Tandem mirror experiments in GAMMA 10
Authors: Tamano T.
Published: July 2002

Confinement of ion cyclotron resonance heating (ICRH) plasmas in the GAMMA 10 tandem mirror [Phys. Rev. Lett. 55, 159 (1985)] has been investigated. Magnetohydrodynamic (MHD) stability is provided by the axisymmetrized minimum-B system. Ion confining and thermal barrier potentials are produced only by electron cyclotron resonance heating (ECRH). Ions are heated to several keV and hot ion modes, where Ti/Te≳(mi/me)1/3, are produced. Ion pressure in the central cell increases approximately linearly both with the power radiated from the antennas and with the magnetic field. A record ion temperature of about 10 keV is obtained at the maximum magnetic field (∼0.57 T). Thermonuclear fusion neutrons are detected in a deuterium/hydrogen mixture plasma for the first time in a tandem mirror. In typical GAMMA 10 operations, strong radial electric fields are naturally produced, and density fluctuations are suppressed. Axial confinement of the core plasma is consistent with the classical potential confinement, indicating radial confinement is better than axial confinement.
Influence of external inhomogeneous static fields on interaction between beam of charged particles and packet of electromagnetic waves
Authors: Fraiman G. M. , Kostyukov I. Yu.
Published: July 2002

The generalized form of Madey’s [Nuovo Cimento B 50, 64 (1979)] theorem is derived. The obtained results are used to analyze the influence of inhomogeneous electric and magnetic fields on an interaction between a beam of charged particles and a packet of electromagnetic waves. The presence of the external static fields can lead not only to the change in the damping rate of the wave packet but also to the reversal of the effect sign that is the pumping of the packet by the beam. The expression for the beam–waves energy transfer can be generalized to take into account ponderomotive forces. This interaction is illustrated by several examples: the interaction of the electron beam with Langmuir soliton, the interaction in the magnetic field with parabolic profile, and in the magnetic mirror with linear profile of the field.
Low-power fast wave antenna loading as a radio-frequency sheath diagnostic
Authors: D’Ippolito D. A. , Myra J. R.
Published: July 2002

Radio-frequency (RF) sheaths induced by the RF E∥ component are a ubiquitous feature of Ion Cyclotron Range of Frequency (ICRF) heating and current drive. An important consequence of RF sheaths is the power dissipation, Psh, caused by ions accelerated in the rectified sheath potential and flowing into material boundaries, such as the antenna structure and nearby limiters. It is shown that the RF sheath-power dissipation yields an antenna loading resistance RL larger than the usual fast wave (FW) loading at very low RF power PRF (typically below 100 kW), because Psh scales as ‖Erf‖, whereas the FW coupled power scales as ‖Erf‖2. The curve RL(PRF) has a maximum at PRF=0 and rapidly decreases with power until asymptoting at the usual FW loading. The ratio RL(0)/RL(∞) is a measure of the average RF sheath voltage on the antenna and nearby limiter surfaces. It is suggested that this technique could be used to measure the RF sheath properties of different antennas or operational regimes (e.g., different phasings) before attempting high-power operation. A generalized loading model is applied to interpret recent measurements on the DIII-D tokamak [Plasma Physics and Controlled Nuclear Fusion Research 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. I, p. 69] for a four-strap antenna with and without a Faraday screen. The possible use of this effect as a diagnostic for the scrape-off layer density is also discussed.
On the higher-order nonlinear corrections to the theory of plasma emission by a nonlinear beam instability
Authors: Yoon Peter H.
Published: July 2002

A recent alternative theory of electromagnetic radiation with frequency in the vicinity of plasma frequency and/or its harmonic, put forth by the present author, invokes a new type of nonlinear beam-plasma instability. The new theory was originally formulated by retaining the second-order nonlinear response of the plasma only. However, in a general nonlinear instability theory it is well known that the third-order correction can have a contribution of the same order of magnitude as the second-order nonlinearity. This article examines the validity of the original formulation of the nonlinear beam instability by reformulating the problem, keeping the full second- and third-order nonlinear responses of the plasma. In the final analysis, however, it is found that the third-order nonlinear correction can indeed be neglected, and that the original formulation of the problem is justified.
Role of electron clusters—Ectons—in the breakdown of solid dielectrics
Authors: Lisitsyn I. V. , Akiyama H. , Mesyats G. A.
Published: July 2002

A new approach is proposed for the description of early breakdown phenomena in solid dielectrics based on the appearance and action of the ectons—electron clusters in the contact point metal–solid dielectric–insulating liquid. An ecton is a result of the electric microexplosion of the electrode inhomogeneity at the triple point by the prebreakdown current described as the displacement current in a dynamic plasma-to-ground capacitor. Ecton appearance becomes possible due to the existence of partial flashover with plasma formation in these points. An ecton is a high-power source of charged particles and pulsed pressure. Injection of the charged particles into a solid dielectric and its local mechanical destruction by the pressure pulses result finally in the breakdown of the solid dielectric.
Sheared-flow generalization of the Harris sheet
Authors: Mahajan S. M. , Hazeltine R. D.
Published: July 2002

A novel, exact class of solutions to the Vlasov–Maxwell system, with self-generated magnetic fields and nonuniform plasma flows, are constructed. It is shown that a gyrotropic distribution function (independent of gyrophase) does not allow equilibrium shear flow; introduction of agyrotropy is essential for the maintenance of spatially nonuniform velocity fields. The new self-consistent sheared-flow solutions include the shearless Harris sheet [E. G. Harris, Nuovo Cimento 23, 117 (1962)] solution as a special case. These equilibria are likely to be relevant to a variety of astrophysical flows (most natural flows are sheared) and to a better understanding of the laboratory phenomena observed, for example, in the device MRX [Magnetic Reconnection Experiment, M. Yamada, H. Ji, S. Hsu, T. Carter, R. Kulsrud, N. Bretz, F. Jodes, Y. Ono, and F. Perkins, Phys. Plasmas 4, 1936 (1997)] designed to study magnetic reconnection.
Solid-state experiments at high pressure and strain rate
Authors: Kalantar D. H. , Remington B. A. , Colvin J. D. , Mikaelian K. O. , Weber S. V. , Wiley L. G. , Wark J. S. , Loveridge A. , Allen A. M. , Hauer A. A. , Meyers M. A.
Published: July 2002

Experiments have been developed using high powered laser facilities to study the response of materials in the solid state under extreme pressures and strain rates. Details of the target and drive development required for solid-state experiments and results from two separate experiments are presented. In the first, thin foils were compressed to a peak pressure of 180 GPa and accelerated. A pre-imposed modulation at the embedded Rayleigh–Taylor unstable interface was observed to grow. The growth rates were fluid-like at early time, but suppressed at later time. This result is suggestive of the theory of localized heating in shear bands, followed by conduction of the heat into the bulk material, allowing for recovery of the bulk material strength. In the second experiment, the response of Si was studied by dynamic x-ray diffraction. The crystal was observed to respond with uni-axial compression at a peak pressure 11.5–13.5 GPa.
Theory of ion holes associated with electron-acoustic vortices
Authors: Jovanović D. , Shukla P. K. , Schamel H.
Published: July 2002

The unified theory of ion holes and electron-acoustic vortices is presented. The ion Vlasov equation, coupled with the hydrodynamic equations for electrons via the Poisson equation is solved self-consistently and a novel type of nonlinear structures is found, which has the form of a quasi two-dimensional density rarefaction that is spatially localized by the nonlinearity resulting from the ion trapping in the negative potential. The perpendicular dynamics are determined by the trapping of the electron fluid in the form of vortices by the E⃗×B⃗ convection. The results are in good agreement with the cavities observed in the auroral region by the Freja satellite.
n-MoSe2/p-WSe2 heterojunctions
Authors: Späh R. , Lux-Steiner M. , Obergfell M. , Bucher E. , Wagner S.
Published: July 2002

The preparation of n-MoSe2/p-WSe2 heterojunctions by epitaxial growth of WSe2 (Eg=1.16 eV) on MoSe2 (Eg=1.06 eV) substrates is reported. The two semiconductors are nearly lattice matched along their hexagonal (001) base plane with Δa/a=0.25%. Diode capacitance-voltage measurements show that the band edges of MoSe2 and WSe2 are aligned within ∼0.1 eV. The diode forward current at room temperature is carried by recombination in the depletion region.
Femtosecond carrier dynamics in GaAs
Authors: Lin W. Z. , Fujimoto L. G. , Ippen E. P. , Logan R. A.
Published: July 2002

Femtosecond carrier dynamics in GaAs and Al0.3Ga0.7As are investigated using pump probe measurements of transient absorption saturation. Pulses of 35 fs duration are used both to excite carriers and to investigate their subsequent scattering out of their initial optically excited states. A two-component ultrafast relaxation is observed. In GaAs the initial rapid relaxation occurs on a time scale of 10–35 fs. Measurements performed in Al0.3Ga0.7As indicate that this initial process slows significantly to 130–170 fs for increasing band gap.
Formation of epitaxial layers of Ge on Si substrates by Ge implantation and oxidation
Authors: Fathy D. , Holland O. W. , White C. W.
Published: July 2002

Thin epitaxial layers of Ge-Si alloys have been formed on Si(100) substrates by steam oxidation of Ge-implanted samples. During the oxidation, the Ge is totally piled up ahead of the SiO2/Si interface. This segregation of Ge leads to the formation of a distinct, Ge-rich layer which is epitaxial with the underlying Si. The thickness of the Ge layer is dependent on the implantation dose. This layer and its two bounding interfaces with the oxide and Si are characterized as a function of the implantation dose and energy, using Rutherford backscattering and high-resolution transmission electron microscopy.
Magnetic resonance, digital image analysis, and permeability of porous media
Authors: Straley Christian , Matteson Abigail , Feng Sechao , Schwartz Lawrence M. , Kenyon William E. , Banavar Jayanth R.
Published: July 2002

The results of an experimental and theoretical study of consolidated, acid-cleaned fused glass beads are presented. Measurements of the spin-lattice lifetime, permeability, and capillary pressure curves in conjunction with digital analysis of scanning electron microscope images and theoretical modeling lead to a description of this porous material consistent with the fast diffusion picture of nuclear magnetic relaxation.
Life extension in
Drosophila
by feeding a drug
Authors: Kang Hyung-Lyun , Benzer Seymour , Min Kyung-Tai
Published: July 2002

We report that feeding
Drosophila
throughout adulthood with 4-phenylbutyrate (PBA) can significantly increase lifespan, without diminution of locomotor vigor, resistance to stress, or reproductive ability. Treatment for a limited period, either early or late in adult life, is also effective. Flies fed PBA show a global increase in histone acetylation as well as a dramatically altered pattern of gene expression, including induction or repression of numerous genes. The delay in aging may result from the altered physiological state.
Forced engagement of a RNA/protein complex by a chemical inducer of dimerization to modulate gene expression
Authors: Harvey Isabelle , Garneau Philippe , Pelletier Jerry
Published: July 2002

A general strategy is described for forcing the engagement of an RNA/protein complex by using small-molecule ligands. A bivalent molecule was created by linking a protein-binding ligand to an RNA-binding ligand. On presentation of the chemical inducer of dimerization to the RNA by the protein, cooperative binding ensued, resulting in higher-affinity complexes. When the chemical inducer of dimerization was used to target the protein to an mRNA template, the resulting RNA/protein complex was sufficiently stable to inhibit mRNA translation. This approach provides a logic to modulate gene expression by using small-molecule ligands to recruit protein surfaces to mRNAs.
Visualization of functionally activated circuitry in the brain
Authors: Wilson Yvette , Nag Nupur , Davern Pamela , Oldfield Brian J. , McKinley Michael J. , Greferath Ursula , Murphy Mark
Published: July 2002

We have used a transgenic approach to visualize functionally activated neurons and their projections. The transgenic mice contain a
tau-lacZ
fusion gene regulated by the promoter for c
-fos
, an immediate early gene that is rapidly induced in neurons after functional stimulation. Constitutive expression of β-galactosidase (β-gal), the
lacZ
product, was low and in accord with previous reports of c-
fos
expression. However, expression of β-gal in positive neurons was clearly in cell bodies, axons, and dendrites. Treatment of the mice with kainic acid, a strong inducer of c-
fos
expression, resulted in high induction of β-gal. β-gal was induced in the same defined populations of neurons in the brain as those that express c-
fos
after kainic acid induction. Furthermore, the pattern of β-gal expression within the neurons changed over time after kainic acid treatment. Early after kainate treatment, β-gal was found mainly in cell bodies; at later times, expression extended further along the neuronal processes. This expression pattern is consistent with induction and anterograde transport of the Fos-Tau-β-gal protein in the neurons. To test whether a functionally activated pathway could be visualized, transgenic mice were deprived of water, which activates nuclei involved in body fluid homeostasis. β-gal induction was traced in neurons and their processes in the lamina terminalis, in magnocellular neurons of the supraoptic and paraventricular nuclei, and in their projections to the posterior pituitary gland. This strategy allowed the mapping of an activated osmoregulatory pathway. This transgenic approach may have general application in the mapping of functionally activated circuitry in the brain.
Quorum-sensing regulators control virulence gene expression in
Vibrio cholerae
Authors: Zhu Jun , Miller Melissa B. , Vance Russell E. , Dziejman Michelle , Bassler Bonnie L. , Mekalanos John J.
Published: July 2002

The production of virulence factors including cholera toxin and the toxin-coregulated pilus in the human pathogen
Vibrio cholerae
is strongly influenced by environmental conditions. The well-characterized ToxR signal transduction cascade is responsible for sensing and integrating the environmental information and controlling the virulence regulon. We show here that, in addition to the known components of the ToxR signaling circuit, quorum-sensing regulators are involved in regulation of
V. cholerae
virulence. We focused on the regulators LuxO and HapR because homologues of these two proteins control quorum sensing in the closely related luminous marine bacterium
Vibrio harveyi
. Using an infant mouse model, we found that a
luxO
mutant is severely defective in colonization of the small intestine. Gene arrays were used to profile transcription in the
V. cholerae
wild type and the
luxO
mutant. These studies revealed that the ToxR regulon is repressed in the
luxO
mutant, and that this effect is mediated by another negative regulator, HapR. We show that LuxO represses
hapR
expression early in log-phase growth, and constitutive expression of
hapR
blocks ToxR-regulon expression. Additionally, LuxO and HapR regulate a variety of other cellular processes including motility, protease production, and biofilm formation. Together these data suggest a role for quorum sensing in modulating expression of blocks of virulence genes in a reciprocal fashion
in vivo
.
Analysis of gene expression during
myc
oncogene-induced lymphomagenesis in the bursa of Fabricius
Authors: Neiman Paul E. , Ruddell Alanna , Jasoni Christine , Loring Gil , Thomas Sandra Jo , Brandvold Kimberly A. , Lee Ruey-min , Burnside Joan , Delrow Jeffrey
Published: July 2002

The transcriptional effects of deregulated
myc
gene
overexpression are implicated in tumorigenesis in a spectrum of
experimental and naturally occurring neoplasms. In follicles of the
chicken bursa of Fabricius,
myc
induction of B-cell
neoplasia requires a target cell population present during early bursal
development and progresses through preneoplastic transformed follicles
to metastatic lymphomas. We developed a chicken immune system cDNA
microarray to analyze broad changes in gene expression that occur
during normal embryonic B-cell development and during
myc
-induced neoplastic transformation in the bursa. The
number of mRNAs showing at least 3-fold change was greater during
myc
-induced lymphomagenesis than during normal
development, and hierarchical cluster analysis of expression patterns
revealed that levels of several hundred mRNAs varied in concert with
levels of
myc
overexpression. A set of 41 mRNAs were
most consistently elevated in
myc
-overexpressing
preneoplastic and neoplastic cells, most involved in processes thought
to be subject to regulation by Myc. The mRNAs for another cluster of
genes were overexpressed in neoplasia independent of
myc
expression level, including a small subset with the expression
signature of embryonic bursal lymphocytes. Overexpression of
myc
, and some of the genes overexpressed with
myc
, may be important for generation of preneoplastic
transformed follicles. However, expression profiles of late metastatic
tumors showed a large variation in concert with
myc
expression levels, and some showed minimal
myc
overexpression. Therefore, high-level
myc
overexpression
may be more important in the early induction of these lymphomas than in
maintenance of late-stage metastases.
Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway
Authors: Baldassarre Gustavo , Fedele Monica , Battista Sabrina , Vecchione Andrea , Klein-Szanto Andres J. P. , Santoro Massimo , Waldmann Thomas A. , Azimi Nazli , Croce Carlo M. , Fusco Alfredo
Published: July 2002

Rearrangements of the high mobility group protein I-C (HMGI-C) gene, consisting in the loss of the carboxyl-terminal tail, have been frequently detected in benign human tumors of mesenchymal origin. We have previously demonstrated that transgenic (TG) mice carrying a truncated HMGI-C construct (HMGI-C/T) exhibit a giant phenotype together with a predominantly abdominal/pelvic lipomatosis. Here, we report that HMGI-C/T TG mice develop natural killer (NK)-T/NK cell lymphomas starting from 12 months of age. We found an increased expression of IL-2 and IL-15 proteins and their receptors in these lymphomas, and we demonstrate that HMGI-C/T protein positively regulates their expression
in vitro
. Therefore, the HMGI-C/T-mediated chronic stimulation of the IL-2/IL-15 pathway could be responsible for the onset of NK-T/NK cell lymphomas in HMGI-C/T TG mice.
Comparative morphology and paleobiology of Middle Pleistocene human remains from the Bau de l'Aubesier, Vaucluse, France
Authors: Lebel Serge , Trinkaus Erik , Faure Martine , Fernandez Philippe , Guérin Claude , Richter Daniel , Mercier Norbert , Valladas Helène , Wagner Günther A.
Published: July 2002

The discovery of later Middle Pleistocene human remains from the
Bau de l'Aubesier, France reinforces an evolutionary model of the
gradual accumulation of Neandertal-derived facial and dental features
during the Middle Pleistocene of the northwestern Old World. The
pronounced maxillary incisor beveling of Aubesier 4 helps to extend the
antiquity of nondietary use of the anterior dentition. The
interproximal “toothpick” groove on the Aubesier 10 molar
increases the sample for these lesions. The pathological loss of the
mandibular dentition of Aubesier 11 indicates advanced antemortem
masticatory impairment, at a level previously undocumented before the
Late Pleistocene. These remains support a view of later Middle
Pleistocene humans able to support debilitated individuals despite the
considerable use of their bodies to accomplish routine activities.
Leptin as a modulator of sweet taste sensitivities in mice
Authors: Kawai Kirio , Sugimoto Kumiko , Nakashima Kiyohito , Miura Hirohito , Ninomiya Yuzo
Published: July 2002

Leptin acts as a potent inhibitory factor against obesity by
regulating energy expenditure, food intake, and adiposity. The obese
diabetic
db
/
db
mouse, which has defects
in leptin receptor, displays enhanced neural responses and elevated
behavioral preference to sweet stimuli. Here, we show the effects of
leptin on the peripheral taste system. An administration of leptin into
lean mice suppressed responses of peripheral taste nerves (chorda
tympani and glossopharyngeal) to sweet substances (sucrose and
saccharin) without affecting responses to sour, salty, and bitter
substances. Whole-cell patch-clamp recordings of activities of taste
receptor cells isolated from circumvallate papillae (innervated by the
glossopharyngeal nerve) demonstrated that leptin activated outward
K
+
currents, which resulted in hyperpolarization of taste
cells. The
db
/
db
mouse with impaired
leptin receptors showed no such leptin suppression. Taste tissue
(circumvallate papilla) of lean mice expressed leptin-receptor mRNA and
some of the taste cells exhibited immunoreactivities to antibodies of
the leptin receptor. Taken together, these observations suggest that
the taste organ is a peripheral target for leptin, and that leptin may
be a sweet-sensing modulator (suppressor) that may take part in
regulation of food intake. Defects in this leptin suppression system in
db
/
db
mice may lead to their enhanced
peripheral neural responses and enhanced behavioral preferences for
sweet substances.
Retrovirus-mediated gene transfer of
MLL-ELL
transforms primary myeloid progenitors and causes acute myeloid leukemias in mice
Authors: Lavau Catherine , Luo Roger T. , Du Changchun , Thirman Michael J.
Published: July 2002

The
MLL-ELL
fusion gene results from the
translocation t(11;19)(q23;p13.1) that is associated with
de
novo
and therapy-related acute myeloid leukemia. To study its
transforming properties, we retrovirally transduced primary murine
hematopoietic progenitors and assessed their growth properties both
in vitro
and
in vivo
.
MLL-ELL
increased the proliferation of myeloid
colony-forming cells in methylcellulose cultures upon serial replating,
whereas overexpression of
ELL
alone had no effect. We
reconstituted lethally irradiated congenic mice with bone marrow
progenitors transduced with
MLL-ELL
or the control MIE
vector encoding the enhanced green fluorescent protein. When the
peripheral blood of the mice was analyzed 11–13 weeks
postreconstitution, we found that the engraftment of the
MLL-ELL-
transduced cells was superior to that of the MIE
controls. At this time point, the contribution of the donor cells was
normally distributed among the myeloid and nonmyeloid compartments.
Although all of the MIE animals (
n
= 10) remained
healthy for more than a year, all of the
MLL-ELL
mice
(
n
= 20) succumbed to monoclonal or pauciclonal
acute myeloid leukemias within 100–200 days. The leukemic cells were
readily transplantable to secondary recipients and could be established
as immortalized cell lines in liquid cultures. These studies
demonstrate the enhancing effect of
MLL-ELL
on the
proliferative potential of myeloid progenitors as well as its causal
role in the genesis of acute myeloid leukemias.
Interactions of protein antigens with antibodies.
Authors: Davies D R , Cohen G H
Published: July 2002

There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other protein-protein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogen-bond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding. For the most studied antigen, lysozyme, the epitopes for four antibodies occupy approximately 45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens.
Novel human DNA alkyltransferases obtained by random substitution and genetic selection in bacteria.
Authors: Christians F C , Loeb L A
Published: July 2002

DNA repair alkyltransferases protect organisms against the cytotoxic, mutagenic, and carcinogenic effects of alkylating agents by transferring alkyl adducts from DNA to an active cysteine on the protein, thereby restoring the native DNA structure. We used random sequence substitutions to gain structure-function information about the human O6-methylguanine-DNA methyltransferase (EC 2.1.1.63), as well as to create active mutants. Twelve codons surrounding but not including the active cysteine were replaced by a random nucleotide sequence, and the resulting random library was selected for the ability to provide alkyltransferase-deficient Escherichia coli with resistance to the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Few amino acid changes were tolerated in this evolutionarily conserved region of the protein. One mutation, a valine to phenylalanine change at codon 139 (V139F), was found in 70% of the selected mutants; in fact, this mutant was selected much more frequently than the wild type. V139F provided alkyltransferase-deficient bacteria with greater protection than the wild-type protein against both the cytotoxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine, increasing the D37 over 4-fold and reducing the mutagenesis rate 2.7-5.5-fold. This mutant human alkyltransferase, or others similarly created and selected, could be used to protect bone marrow cells from the cytotoxic side effects of alkylation-based chemotherapeutic regimens.
The level of mRNA encoding the amphotropic retrovirus receptor in mouse and human hematopoietic stem cells is low and correlates with the efficiency of retrovirus transduction.
Authors: Orlic D , Girard L J , Jordan C T , Anderson S M , Cline A P , Bodine D M
Published: July 2002

The low level of amphotropic retrovirus-mediated gene transfer into human hematopoietic stem cells (HSC) has been a major impediment to gene therapy for hematopoietic diseases. In the present study, we have examined amphotropic retrovirus receptor (amphoR) and ecotropic retrovirus receptor mRNA expression in highly purified populations of mouse and human HSC. Murine HSC with low to undetectable levels of amphoR mRNA and relatively high levels of ecotropic retrovirus receptor mRNA were studied. When these HSC were analyzed simultaneously for ecotropic and amphotropic retrovirus transduction, ecotropic provirus sequences were detected in 10 of 13 long-term repopulated animals, while amphotropic proviral sequences were detected in only one recipient. A second distinct population of murine HSC were isolated that express 3-fold higher levels of amphoR mRNA. When these HSC were analyzed simultaneously for ecotropic and amphotropic retrovirus transduction, 11 of 11 repopulated mice contained ecotropic provirus and 6 of 11 contained amphotropic provirus sequences, a significant increase in the amphotropic retrovirus transduction (P = 0.018). These results indicate that, among the heterogeneous populations of HSC present in adult mouse bone marrow, the subpopulation with the highest level of amphoR mRNA is more efficiently transduced by amphotropic retrovirus. In a related study, we found low levels of human amphoR mRNA in purified populations of human HSC (CD34+ CD38-) and higher levels in committed progenitor cells (CD34+ CD38+). We conclude that the amphoR mRNA level in HSC correlates with amphotropic retrovirus transduction efficiency.
Glutamate transport in
Rhodobacter sphaeroides
is mediated by a novel binding protein-dependent secondary transport system
Authors: Jacobs Mariken H. J. , van der Heide Tiemen , Driessen Arnold J. M. , Konings Wil N.
Published: July 2002

Growth of a glutamate transport-deficient mutant of
Rhodobacter sphaeroides
on glutamate as sole carbon and
nitrogen source can be restored by the addition of millimolar amounts
of Na
+
. Uptake of glutamate (
K
t
of 0.2 μM) by the mutant strictly requires Na
+
(
K
m
of 25 mM) and is inhibited by ionophores
that collapse the proton motive force (pmf). The activity is
osmotic-shock-sensitive and can be restored in spheroplasts by the
addition of osmotic shock fluid. Transport of glutamate is also
observed in membrane vesicles when Na
+
, a proton motive
force, and purified glutamate binding protein are present. Both
transport and binding is highly specific for glutamate. The
Na
+
-dependent glutamate transporter of
Rb.
sphaeroides
is an example of a secondary transport system that
requires a periplasmic binding protein and may define a new family of
bacterial transport proteins.
The tumorigenic potential and cell growth characteristics of p53-deficient cells are equivalent in the presence or absence of Mdm2
Authors: Jones Stephen N. , Sands Arthur T. , Hancock Amy R. , Vogel Hannes , Donehower Lawrence A. , Linke Steven P. , Wahl Geoffrey M. , Bradley Allan
Published: July 2002

The Mdm2 oncoprotein forms a complex with the p53 tumor suppressor
protein and inhibits p53-mediated regulation of heterologous gene
expression. Recently, Mdm2 has been found to bind several other
proteins that function to regulate cell cycle progression, including
the E2F-1/DP1 transcription factor complex and the retinoblastoma
tumor-suppressor protein. To determine whether Mdm2 plays a role in
cell cycle control or tumorigenesis that is distinct from its ability
to modulate p53 function, we have examined and compared both the
in vitro
growth characteristics of p53-deficient and
Mdm2/p53-deficient fibroblasts, and the rate and spectrum of tumor
formation in p53-deficient and Mdm2/p53-deficient mice. We find no
difference between p53-deficient fibroblasts and Mdm2/p53-deficient
fibroblasts either in their rate of proliferation in culture or in
their survival frequency when treated with various genotoxic agents.
Cell cycle studies indicate no difference in the ability of the two
cell populations to enter S phase when treated with DNA-damaging agents
or nucleotide antimetabolites, and p53-deficient fibroblasts and
Mdm2/p53-deficient fibroblasts exhibit the same rate of spontaneous
immortalization following long-term passage in culture. Finally,
p53-deficient mice and Mdm2/p53-deficient mice display the same
incidence and spectrum of spontaneous tumor formation
in
vivo
. These results demonstrate that deletion of Mdm2 has no
additional effect on cell proliferation, cell cycle control, or
tumorigenesis when p53 is absent.
Characterization of serum amyloid A protein mRNA expression and secondary amyloidosis in the domestic duck
Authors: Guo Ju-Tao , Aldrich Carol E. , Mason William S. , Pugh John C.
Published: July 2002

Secondary amyloidosis is a common disease of water fowl and is characterized by the deposition of extracellular fibrils of amyloid A (AA) protein in the liver and certain other organs. Neither the normal role of serum amyloid A (SAA), a major acute phase response protein, nor the causes of secondary amyloidosis are well understood. To investigate a possible genetic contribution to disease susceptibility, we cloned and sequenced SAA cDNA derived from livers of domestic ducks. This revealed that the three C-terminal amino acids of SAA are removed during conversion to insoluble AA fibrils. Analysis of SAA cDNA sequences from several animals identified a distinct genetic dimorphism that may be relevant to susceptibility to secondary amyloid disease. The duck genome contained a single copy of the SAA gene that was expressed in liver and lung tissue of ducklings, even in the absence of induction of acute phase response. Genetic analysis of heterozygotes indicated that only one SAA allele is expressed in livers of adult birds. Immunofluorescence staining of livers from adult ducks displaying early symptoms of amyloidosis revealed what appear to be amyloid deposits within hepatocytes that are expressing unusually high amounts of SAA protein. This observation suggests that intracellular deposition of AA may represent an early event during development of secondary amyloidosis in older birds.
Red blood cell adhesion on a solid/liquid interface
Authors: Lavalle Ph. , Stoltz J.-F. , Senger B. , Voegel J.-C. , Schaaf P.
Published: July 2002

Red blood cells (RBCs), previously fixed with glutaraldehyde,
adhere to glass slides coated with fibrinogen. The RBC deposition
process on the horizontal glass surface is investigated by analyzing
the relative surface covered by the RBCs, as well as the variance of
this surface coverage, as a function of the concentration of particles.
This study is performed by optical microscopy and image analysis. A
model, derived from the classical random sequential adsorption model,
has been developed to account for the experimental results. This model
highlights the strong influence of the hydrodynamic interactions during
the deposition process.
Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites.
Authors: Herzberg O , Chen C C , Kapadia G , McGuire M , Carroll L J , Noh S J , Dunaway-Mariano D
Published: July 2002

The crystal structure of pyruvate phosphate dikinase, a histidyl multiphosphotransfer enzyme that synthesizes adenosine triphosphate, reveals a three-domain molecule in which the phosphohistidine domain is flanked by the nucleotide and the phosphoenolpyruvate/pyruvate domains, with the two substrate binding sites approximately 45 angstroms apart. The modes of substrate binding have been deduced by analogy to D-Ala-D-Ala ligase and to pyruvate kinase. Coupling between the two remote active sites is facilitated by two conformational states of the phosphohistidine domain. While the crystal structure represents the state of interaction with the nucleotide, the second state is achieved by swiveling around two flexible peptide linkers. This dramatic conformational transition brings the phosphocarrier residue in close proximity to phosphoenolpyruvate/pyruvate. The swiveling-domain paradigm provides an effective mechanism for communication in complex multidomain/multiactive site proteins.
Progress toward chemical accuracy in the computer simulation of condensed phase reactions.
Authors: Bash P A , Ho L L , MacKerell A D , Levine D , Hallstrom P
Published: July 2002

We describe a procedure for the generation of chemically accurate computer-simulation models to study chemical reactions in the condensed phase. The process involves (i) the use of a coupled semiempirical quantum and classical molecular mechanics method to represent solutes and solvent, respectively; (ii) the optimization of semiempirical quantum mechanics (QM) parameters to produce a computationally efficient and chemically accurate QM model; (iii) the calibration of a quantum/classical microsolvation model using ab initio quantum theory; and (iv) the use of statistical mechanical principles and methods to simulate, on massively parallel computers, the thermodynamic properties of chemical reactions in aqueous solution. The utility of this process is demonstrated by the calculation of the enthalpy of reaction in vacuum and free energy change in aqueous solution for a proton transfer involving methanol, methoxide, imidazole, and imidazolium, which are functional groups involved with proton transfers in many biochemical systems. An optimized semiempirical QM model is produced, which results in the calculation of heats of formation of the above chemical species to within 1.0 kcal/mol (1 kcal = 4.18 kJ) of experimental values. The use of the calibrated QM and microsolvation QM/MM (molecular mechanics) models for the simulation of a proton transfer in aqueous solution gives a calculated free energy that is within 1.0 kcal/mol (12.2 calculated vs. 12.8 experimental) of a value estimated from experimental pKa values of the reacting species.
Dressed polyions, counterion condensation, and adsorption excess in polyelectrolyte solutions.
Authors: Mohanty U , Ninham B W , Oppenheim I
Published: July 2002

The phenomenon of Manning-Oosawa counterion condensation is given an explicit statistical mechanical and qualitative basis via a dressed polyelectrolyte formalism in connection with the topology of the electrostatic free-energy surface and is derived explicitly in terms of the adsorption excess of ions about the polyion via the nonlinear Poisson-Boltzmann equation. The approach is closely analogous to the theory of ion binding in micelles. Our results not only elucidate a Poisson-Boltzmann analysis, which shows that a fraction of the counterions lie within a finite volume around the polyion even if the volume of the system tends towards infinity, but also provide a direct link between Manning's theta-the number of condensed counterions for each polyion site-and a statistical thermodynamic quantity, namely, the adsorption excess per monomer.
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH
2
-terminal kinase
Authors: Tournier Cathy , Whitmarsh Alan J. , Cavanagh Julie , Barrett Tamera , Davis Roger J.
Published: July 2002

The c-Jun NH
2
-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by phosphorylation on Thr and Tyr. Here we report the molecular cloning of a new member of the mammalian MAP kinase kinase group (MKK7) that functions as an activator of JNK.
In vitro
protein kinase assays demonstrate that MKK7 phosphorylates and activates JNK, but not the p38 or extracellular signal-regulated kinase groups of MAP kinase. Expression of MKK7 in cultured cells causes activation of the JNK signal transduction pathway. MKK7 is therefore established to be a novel component of the JNK signal transduction pathway.