bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of generalized Poisson and Nambu–Poisson brackets
Authors: Ibáñez Raúl , de León Manuel , Marrero Juan C. , de Diego David Martı́n
Published: July 2002

A unified setting for generalized Poisson and Nambu–Poisson brackets is discussed. It is proved that a Nambu–Poisson bracket of even order is a generalized Poisson bracket. Characterizations of Poisson morphisms and generalized infinitesimal automorphisms are obtained as coisotropic and Lagrangian submanifolds of product and tangent manifolds, respectively.
Darboux and binary Darboux transformations for the nonautonomous discrete KP equation
Authors: Willox R. , Tokihiro T. , Satsuma J.
Published: July 2002

It is shown how Darboux and binary Darboux transformations for a nonautonomous discrete KP equation can be obtained from fermion analysis. This equation is obtained by considering a generalized Miwa transformation; it is also shown to be linked to the discrete KP equation by a special gauge transformation. The Darboux and binary Darboux transformations are used to discuss general classes of solutions in the form of Casorati- and Gramm-type determinants. N-soliton solutions are discussed as well.
Past and future of inverse problems
Authors: Sabatier Pierre C.
Published: July 2002

Inverse problems are those where a set of measured results is analyzed in order to get as much information as possible on a “model” which is proposed to represent a system in the real world. Exact inverse problems are related to most parts of mathematics. Applied inverse problems are the keys to other sciences. Hence the field, which is very wealthy, yields the best example of interdisciplinary research but it has nevertheless a strong individuality. The obtained results and explored directions of the 20th century are sketched in this review, with attempts to predict their evolution.
Dispersion, convection, and reaction in porous media
Authors: Mauri Roberto
Published: July 2002

The problem of transport of a reactive solute in a porous medium by convection and diffusion is studied for the case in which the solute particles undergo a first-order chemical reaction on the surface of the bed. Assuming that the geometry is periodic, the method of homogenization is applied, showing explicitly that the effective equation is given by a Kramers–Moyal expansion, i.e., a partial differential equation of infinite order in which the nth term is the product of the nth gradient of the mean concentration by an nth-order constant tensor. The effective values of reactivity, solute velocity, diffusivity, and of all the tensorial coefficients in the expansion are independent of the initial solute distribution and are expressed in terms of Peclet’s and Damkohler’s numbers, Pe=aV/D and Da=ak/D, respectively, where a is the cell size, V is the solvent mean velocity, D is the solute molecular diffusivity, and k is the surface reactivity, showing that they are independent of the initial solute distribution. Since the ratio between two successive terms in the effective equation equals the small ratio ε between the micro- and macrolength scales, truncating the expansion after the nth term allows us to find the effective concentration up to O(εn) terms.

The impact of this fact is exemplified, showing that in the case of a solute flowing in a pipe with small Damkohler number Da, the effective concentration can be determined up to O(Da) terms only if the effective equation includes the skewness term. When Pe and Da are either small or large, after determining a two-parameter expansion of the solution, it is shown that the ratios between the diffusion, convection, and reaction macroscopic characteristic time scales cannot always be inferred through a naive dimensional analysis at the microscale. For example, when Da≫1 we find that the effective reaction rate tends to a constant value, independent of Da. When Pe≫1, Taylor-like dispersion, proportional to Pe2, is obtained when the mean flow is perpendicular to any vector of the reciprocal lattice. If this condition is not satisfied, the result strongly depends on the magnitude of the volume fraction of the bed particles Φ. If Pe−3≪Φ≪1, then the main mechanism causing dispersion is convection alone and the effective diffusivity is proportional to Pe; on the contrary, when Φ≪Pe−3, the effective diffusivity tends to a constant value independent of Pe.
Stability of liquid bridges between equal disks in an axial gravity field
Authors: Slobozhanin Lev A. , Perales José M.
Published: July 2002

equal-diameter solid disks subjected to an axial gravity field of arbitrary intensity is analyzed for all possible liquid volumes. The boundary of the stability region for axisymmetric shapes (considering both axisymmetric and nonaxisymmetric perturbations) have been calculated. It is found that, for sufficiently small Bond numbers, three different unstable modes can appear. If the volume of liquid is decreased from that of an initially stable axisymmetric configuration the bridge either develops an axisymmetric instability (breaking in two drops as already known) or detaches its interface from the disk edges (if the length is smaller than a critical value depending on contact angle), whereas if the volume is increased the unstable mode consists of a nonaxisymmetric deformation. This kind of nonaxisymmetric deformation can also appear by decreasing the volume if the Bond number is large enough. A comparison with other previous partial theoretical analyses is presented, as well as with available experimental results.
The evolution of magnetic fields and plasmas in open field line configurations
Authors: Boozer Allen H.
Published: July 2002

The nonideal behavior of the magnetic field is shown to depend only on the loop voltage, ∮E■dl, in open magnetic configurations. The tying of the plasma to the magnetic field is shown to be a weaker invariant than are the flux and helicity invariants that follow from the ideal form for the field evolution. The surfaces of constant loop voltages are shown to form a set of natural, or invariant, flux surfaces. These invariant flux surfaces are the equivalent in open geometries of the magnetic surfaces of toroidal geometry.
Vacuum magnetic field structure of compact torii
Authors: Soběhart Jorge R.
Published: July 2002

A new class of axisymmetric vacuum field solutions of the Grad–Shafranov equation, which is suitable for describing the field external to a compact torus equilibrium, is presented. In particular, solutions that match straight field lines at infinity are studied.
Transition from toroidal to slab temperature gradient driven modes
Authors: Kim Jin-Yong , Horton Wendell
Published: July 2002

In the local approximation the electrostatic dispersion relation for the (ion or electron) temperature gradient driven modes is solved retaining the full guiding-center resonance condition ω=k∥v∥+k⋅vD (v2⊥,v2∥). Increase of the slab-to-toroidal ratio parameter k∥vT/k⊥vD is shown to directly increase the threshold value of the temperature-to-density gradient parameter ηc. Therefore, the local anomalous heat flux has a strong dependence on the safety factor q when k∥∼1/qR.
Jet stripping of molten metallic coatings
Authors: Ellen C. H. , Tu C. V.
Published: July 2002

The thickness of the coating on a strip produced by modern hot-dip galvanizing lines is controlled with air jets which generate a ‘‘barrier’’ to the molten coating material as it is drawn from its bath by the emerging strip. It is shown that an improved understanding of the process and more accurate predictions may be obtained by modifying the existing theory to include the jet-induced surface shear acting in conjunction with the jet stagnation pressure gradient effect.
Stability of displacement processes in porous media in radial flow geometries
Authors: Yortsos Y. C.
Published: July 2002

The linear stability of certain displacement processes in porous media for two-dimensional radial flows induced by a point source is examined. Both two-phase, immiscible displacement and single-phase miscible displacement in the presence of equilibrium adsorption are discussed. In agreement with Tan and Homsy [Phys. Fluids 30, 1239 (1987)], it is found that disturbances grow or decay algebraically in time. Via appropriate transformations the eigenvalue problems are shown to be identical to those in rectilinear flow geometries with suitably modified base states and parameters. Thus several stability features are inferred directly from the analysis in rectilinear geometries. The results indicate the existence of critical values for the capillary (NCa) or Peclet (Pe) number, above which the displacement is unstable for wavenumbers in a band of finite width. For large NCa or Pe the most dangerous and the highest cutoff modes scale linearly with NCa or Pe. The different scaling found by Tan and Homsy [Phys. Fluids 30, 1239 (1987)] follows directly as a singular limit of the miscible displacement problem in the absence of adsorption.
The nonlinear three-wave interaction with a finite spectral width
Authors: Martins A. M. , Mendonça J. T.
Published: July 2002

The nonlinear interaction of three waves propagating in an infinite plasma with a finite spectral bandwidth is studied. A Hamiltonian formulation of the interaction is used and, with the help of a projection operator method, generalized Langevin equations are derived for the wave field amplitudes. A simple form of the evolution equations, more complete than the usual fixed-phase equations, is obtained when the ballistic term and higher-order corrections of the memory effects in the Langevin equations are neglected. Approximate analytical solutions are derived using a multiple time scale method. These are compared with the results of numerical integration. A number of new qualitative features related to the finite spectral bandwidth are discussed in detail.
Stability of periodic arrays of vortices
Authors: Dauxois Thierry , Fauve Stephan , Tuckerman Laurette
Published: July 2002

The stability of periodic arrays of Mallier–Maslowe or Kelvin–Stuart vortices is discussed. We derive with the energy-Casimir stability method the nonlinear stability of this solution in the inviscid case as a function of the solution parameters and of the domain size. We exhibit the maximum size of the domain for which the vortex street is stable. By adapting a numerical time-stepping code, we calculate the linear stability of the Mallier–Maslowe solution in the presence of viscosity and compensating forcing. Finally, the results are discussed and compared to a recent experiment in fluids performed by Tabeling et al. [Europhy. Lett. 3, 459 (1987)]. Electromagnetically driven counter-rotating vortices are unstable above a critical electric current, and give way to co-rotating vortices. The importance of the friction at the bottom of the experimental apparatus is also discussed.
Flow transitions and combined free and forced convective heat transfer in rotating curved channels: The case of positive rotation
Authors: Wang Liqiu , Cheng K. C.
Published: July 2002

The simultaneous effects of curvature, rotation and heating/cooling in channel flow complicate the flow and heat transfer characteristics beyond those observed in the channels with simple curvature or rotation. The phenomena encountered are examined for steady, hydrodynamically and thermally fully developed flow in square channels. The governing equations are solved numerically by using a finite-volume method. Certain hitherto unknown flow patterns are found. And the results show both the nature of the flow transition and the effect of this transition on the distributions of temperature, friction factor and Nusselt number in a square channel.
An experimental study of deep water plunging breakers
Authors: Perlin Marc , He Jianhui , Bernal Luis P.
Published: July 2002

Plunging breaking waves are generated mechanically on the surface of essentially deep water in a two-dimensional wave tank by superposition of progressive waves with slowly decreasing frequency. The time evolution of the transient wave and the flow properties are measured using several experimental techniques, including nonintrusive surface elevation measurement, particle image velocimetry, and particle tracking velocimetry. The wave generation technique is such that the wave steepness is approximately constant across the amplitude spectrum. Major results include the appearance of a discontinuity in slope at the intersection of the lower surface of the plunging jet and the forward face of the wave that generates parasitic capillary waves; transverse irregularities occur along the upper surface of the falling, plunging jet while the leeward side of the wave remains very smooth and two dimensional; the velocity field is shown to decay rapidly with depth, even in this strongly nonlinear regime, and is similar to that expected from linear theory—the fluid is undisturbed for depths greater than one-half the wavelength; a focusing or convergence of particle velocities are shown to create the jet in the wave crest; vorticity levels determined from the measured, full-field velocity vectors show that the waves are essentially irrotational until incipient breaking occurs; and the magnitude of the largest water particle velocity is about 30% greater than the phase speed of the (equivalent) linear wave.
A round turbulent jet produced by an oscillating diaphragm
Authors: James R. D. , Jacobs J. W. , Glezer A.
Published: July 2002

A round turbulent water jet produced normal to, and at the center of a submerged, resonantly driven diaphragm is investigated experimentally. The jet which is formed without mass injection and is comprised entirely of radially entrained fluid, is present only when the excitation amplitude exceeds a given threshold. Above this excitation level, a small cluster of cavitation bubbles appears near the center of the diaphragm. The bubbles grow, apparently collapse, and then disappear during each oscillation cycle. It is conjectured that the jet is synthesized by time-periodic coalescence of vortex rings that are produced by secondary flow around the bubbles or by the collapse of the bubbles. It is remarkable that even though the jet results from a strong time-periodic excitation and its time-periodic features are detected throughout the present range of measurements, the time-averaged jet structure is similar to that of a conventional turbulent round jet in that the increase in its width and in the inverse of its centerline velocity are both linear functions of the distance from the actuator. In contrast to conventional jets, the present synthetic jets can be manipulated on relatively short time scales that are comparable to the excitation period.
Wake measurements for flow around a sphere in a viscoelastic fluid
Authors: Fabris Drazen , Muller Susan J. , Liepmann Dorian
Published: July 2002

The flow field around a sphere falling at its terminal velocity in a column of viscoelastic non-shear-thinning fluid is experimentally measured with digital particle image velocimetry. The working fluid is an extensively characterized, monodisperse, polystyrene based Boger fluid. The sphere radius relative to the radius of the column of fluid is small (a/rc=0.083). The Weissenberg number (λUt/a) ranges from 0.5 to 14 over which the sphere experiences a drag increase up to 8 times that of the Newtonian flow. The flow field is investigated in detail for We 0.5 to 2.5. A length and width scale is defined for the wake. Over this range of We the wake is found to grow linearly with We and become self-similar in a transverse cross-section of the axial component of the velocity. Streamlines along with extension and rotation rates along those streamlines are also determined.
Planform structure and heat transfer in turbulent free convection over horizontal surfaces
Authors: Theerthan S. Ananda , Arakeri Jaywant H.
Published: July 2002

This paper deals with turbulent free convection in a horizontal fluid layer above a heated surface. Experiments have been carried out on a heated surface to obtain and analyze the planform structure and the heat transfer under different conditions. Water is the working fluid and the range of flux Rayleigh numbers (Ra) covered is 3×107–2×1010. The different conditions correspond to Rayleigh-Bénard convection, convection with either the top water surface open to atmosphere or covered with an insulating plate, and with an imposed external flow on the heated boundary. Without the external flow the planform is one of randomly oriented line plumes. At large Rayleigh number Ra and small aspect ratio (AR), these line plumes seem to align along the diagonal, presumably due to a large scale flow. The side views show inclined dyelines, again indicating a large scale flow. When the external flow is imposed, the line plumes clearly align in the direction of external flow. The nondimensional average plume spacing, Raλ1/3, varies between 40 and 90. The heat transfer rate, for all the experiments conducted, represented as RaδT−1/3, where δT is the conduction layer thickness, varies only between 0.1–0.2, showing that in turbulent convection the heat transfer rates are similar under the different conditions.
A mechanism for beam-driven excitation of ion cyclotron harmonic waves in the Tokamak Fusion Test Reactor
Authors: Dendy R. O. , McClements K. G. , Lashmore-Davies C. N. , Majeski R. , Cauffman S.
Published: July 2002

A mechanism is proposed for the excitation of waves at harmonics of the injected ion cyclotron frequencies in neutral beam-heated discharges in the Tokamak Fusion Test Reactor (TFTR) [Proceedings of the 17th European Conference on Controlled Fusion and Plasma Heating (European Physical Society, Petit-Lancy, Switzerland, 1990), p. 1540]. Such waves are observed to originate from the outer midplane edge of the plasma. It is shown that ion cyclotron harmonic waves can be destabilized by a low concentration of sub-Alfvénic deuterium or tritium beam ions, provided these ions have a narrow distribution of speeds parallel to the magnetic field. Such a distribution is likely to occur in the edge plasma, close to the point of beam injection. The predicted instability gives rise to wave emission at propagation angles lying almost perpendicular to the field. In contrast to the magnetoacoustic cyclotron instability proposed as an excitation mechanism for fusion-product-driven ion cyclotron emission in the Joint European Torus (JET) [Phys. Plasmas 1, 1918 (1994)], the instability proposed here does not involve resonant fast Alfvén and ion Bernstein waves, and can be driven by sub-Alfvénic energetic ions. It is concluded that the observed emission from TFTR can be driven by beam ions.
Lower-hybrid wave collapse
Authors: Robinson P. A. , Melatos A. , Rozmus W.
Published: July 2002

The formation, collapse and arrest of lower-hybrid wave packets are investigated analytically. The three-dimensional structure of the wave packet is incorporated in the analysis and its polarization is studied for the first time. Nonlinear collapse thresholds are obtained via a Hamiltonian formulation and are used in calculating the probability distribution of collapsing wave packet structures as a function of their polarization. Transit-time interaction theory is then used to calculate the arrest scale at which collapse is halted as the waves are damped. It is found that collapse thresholds are lowest for circularly polarized packets, but that nearly linearly polarized ones predominate in collapse because of their greater numbers in the linear phase of the evolution. It is argued that subsonic collapse persists until very near arrest, in accord with recent numerical simulations. Time scale analysis shows that the parallel field structure has difficulty in attaining its self-similar form in the available collapse time, also in accord with simulations. Transit-time theory implies that electrons travelling roughly parallel to the ambient magnetic field can arrest collapse at a scale comparable to that previously estimated for ions; which process dominates depends on the electron and ion temperatures and packet geometry. The resulting arrest scales are found to be in accord with the simulations.
On the origin of the ion acoustic soliton
Authors: Sheridan T. E. , Yi S. , Lonngren K. E.
Published: July 2002

The excitation of ion acoustic solitons by a grid modulated near the ion plasma frequency is studied computationally in a plasma of kinetic ions and Boltzmann electrons. It is found that a large-amplitude, pulse-like, ion acoustic wave is launched from the grid and then amplified via inverse Landau damping. This wave is unstable and decays nonlinearly into an ion acoustic soliton and an ion acoustic wave packet. The model reproduces features observed in the experiment of Yi et al. [Phys. Plasmas 4, 2436 (1997)], confirming its essential correctness. The results are also consistent with Korteweg–de Vries theory.
Determination of the vacuum field resulting from the perturbation of a toroidally symmetric plasma
Authors: Atanasiu C. V. , Boozer A. H. , Zakharov L. E. , Subbotin A. A. , Miron G. I.
Published: July 2002

By using the concept of a surface current, the description and calculation of the stability of modes and the plasma response function are greatly simplified. A robustly accurate and effective method is presented to determine these surface currents, considering that the perturbation is given by toroidally coupled tearing modes. A new form of the normal component of the magnetic field perturbation (B̃n), excited by a tearing mode with toroidal coupling, has been derived in terms of the solution of a hypergeometric differential equation, which is also appropriate in the large toroidal mode number (N) limit. Examples of calculations are given for different plasma cross-sectional shapes, including separatrix configurations.
Guiding of laser pulses in plasma channels created by the ignitor-heater technique
Authors: Volfbeyn P. , Esarey E. , Leemans W. P.
Published: July 2002

Experimental and theoretical investigations of laser guiding in plasma channels are reported. Intense (<5×1017 W/cm2), short (75 fs) laser pulses have been injected and guided in channels produced using a novel ignitor-heater technique, which uses two laser pulses. The ignitor, an ultrashort (<100 fs) laser pulse, is brought to a line focus to ionize the gas jet. The heater pulse (160 ps long) is subsequently used to heat the existing spark via inverse Bremsstrahlung. The hydrodynamic shock expansion creates a channel. This technique allows the creation of slab or cylindrical channels in low atomic number gases, e.g., hydrogen. The channel profile was diagnosed with time resolved longitudinal interferometry. The effects of laser beam size and divergence mismatch at the channel entrance and leakage of the laser energy out of the channel are studied theoretically and experimentally in one and two transverse dimensions. An all-optical channel wake diagnostic based on Fourier domain interferometry is discussed, and a holographic-type inversion technique is proposed to increase the accuracy and reach of this method.
Gyrokinetic field theory
Authors: Sugama H.
Published: July 2002

The Lagrangian formulation of the gyrokinetic theory is generalized in order to describe the particles’ dynamics, as well as the self-consistent behavior of the electromagnetic fields. The gyrokinetic equation for the particle distribution function and the gyrokinetic Maxwell’s equations, for the electromagnetic fields, are both derived from the variational principle for the Lagrangian consisting of the parts of particles, fields, and their interaction. In this generalized Lagrangian formulation, the energy conservation property for the total nonlinear gyrokinetic system of equations is directly shown from Noether’s theorem. This formulation can be utilized in order to derive the nonlinear gyrokinetic system of equations and the rigorously conserved total energy for fluctuations with arbitrary frequencies. Simplified gyrokinetic systems of equations with the conserved energy are obtained from the Lagrangian with the small electron gyroradii, quasineutrality, and linear polarization–magnetization approximations.
Thin-film waveguide magneto-optic isolator
Authors: Wolfe R. , Hegarty J. , Dillon J. F. , Luther L. C. , Celler G. K. , Trimble L. E. , Dorsey C. S.
Published: July 2002

A thin-film waveguide Faraday rotator which provides nonreciprocal polarization rotation of ±45° for light of wavelength 1.45 μm with an extinction ratio of 500:1 has been demonstrated. This isolator structure makes use of laser annealing to reverse the sublattice magnetization and hence the sign of the Faraday effect in localized regions of a (Bi, Ga) yttrium iron garnet film. A novel geometrical pattern was designed for these regions to overcome the effects of the inherent thin-film birefringence.
Native hole trap in bulk GaAs and its association with the double-charge state of the arsenic antisite defect
Authors: Lagowski J. , Lin D. G. , Chen T.-P. , Skowronski M. , Gatos H. C.
Published: July 2002

We have identified a dominant hole trap in p-type bulk GaAs employing deep level transient and photocapacitance spectroscopies. The trap is present at a concentration up to about 4×1016 cm−3, and it has two charge states with energies 0.54±0.02 and 0.77±0.02 eV above the top of the valence band (at 77 K). From the upper level the trap can be photoexcited to a persistent metastable state just as the dominant midgap level, EL2. Impurity analysis and the photoionization characteristics rule out association of the trap with impurities Fe, Cu, or Mn. Taking into consideration theoretical results, it appears most likely that the two charge states of the trap are the single and double donor levels of the arsenic antisite AsGa defect.
Nondestructive depth profiling by spectroscopic ellipsometry
Authors: Vedam K. , McMarr P. J. , Narayan J.
Published: July 2002

It is shown that spectroscopic ellipsometry (SE) studies followed by the regression analysis of the SE data can yield information nondestructively and in a nonperturbing manner on the depth profile of multilayer structure; such as (i) quantitative information on the thickness and the dielectric function of each layer, (ii) the structure (whether crystalline or amorphous) as well as the degree of crystallinity of each layer, (iii) characterization of the oxide layer if present on the specimen, and (iv) microroughness of the surface, if present. Furthermore, it is shown that these results are in excellent agreement with the results obtained on the same specimens using cross-section transmission electron microscopy.
Electrostatic lenses with very small spherical aberration
Authors: Szilagyi M.
Published: July 2002

A class of electrostatic lenses with extremely low spherical aberration is proposed. The axial potential distribution of these lenses has an asymmetric bell-shaped form with a lower potential on the image side. A lens with Cso∞/fo=0.51 is presented as an example. The maximum required electrode voltage is only five times larger than the initial accelerating voltage. At 5 mrad acceptance half-angle, 51 mm focal length, and magnification M=−3.3 the radius of the spherical aberration disk is 6 nm.
Aberrant expression of homeobox gene
HOXA7
is associated with müllerian-like differentiation of epithelial ovarian tumors and the generation of a specific autologous antibody response
Authors: Naora Honami , Montz Fredrick J. , Chai Chee-Yin , Roden Richard B. S.
Published: July 2002

Autologous serum antibodies to molecules that are aberrantly
expressed in tumors represent potential biomarkers for early diagnosis
of cancer. In this study, we identified the homeobox gene
HOXA7
as encoding an antigen in epithelial tumors of the
ovary. These tumors are thought to arise from the simple epithelium
lining the ovarian surface, but they often resemble the specialized
epithelia derived from the müllerian ducts. Expression of HOXA7
was detected in ovarian tumors exhibiting müllerian-like features
and correlated with the generation of anti-HOXA7 antibodies by
patients. In contrast, it was observed that healthy women lack
anti-HOXA7 antibodies (
P
< 0.0001) and that HOXA7
expression is absent from normal ovarian surface epithelium.
Interestingly, HOXA7 expression was detected in the
müllerian-like epithelium lining inclusion cysts in normal
ovaries and in the müllerian duct-derived epithelium of normal
fallopian tubes. Furthermore, ectopic expression of
HOXA7
enhanced the epithelial phenotype of immortalized
ovarian surface epithelial cells, as indicated by the appearance of
cobblestone morphology, induction of E-cadherin expression, and
down-regulation of vimentin. These findings associate aberrant
HOXA7
expression with the müllerian-like
differentiation of epithelial ovarian tumors and suggest diagnostic
utility of serum antibodies to HOXA7.
Increased insulin sensitivity in mice lacking p85β subunit of phosphoinositide 3-kinase
Authors: Ueki Kohjiro , Yballe Claudine M. , Brachmann Saskia M. , Vicent David , Watt John M. , Kahn C. Ronald , Cantley Lewis C.
Published: July 2002

On the basis of
ex vivo
studies using
insulin-responsive cells, activation of a Class IA phosphoinositide
3-kinase (PI3K) seems to be required for a wide variety of cellular
responses downstream of insulin. The Class IA PI3K enzymes are
heterodimers of catalytic and regulatory subunits. In mammals,
insulin-responsive tissues express both the p85α and p85β isoforms
of the regulatory subunit. Surprisingly, recent studies have revealed
that disruption of the p85α gene in the mouse
(
p85
α
−/−
mice) results in hypoglycemia
with decreased plasma insulin, and the
p85
α
+/−
mice exhibit significantly
increased insulin sensitivity. These results suggest either that p85α
negatively regulates insulin signaling, or that p85β, which mediates
the major fraction of Class IA PI3K signaling in the absence of p85α,
is more efficient than p85α in mediating insulin responses. To
address this question, we have generated mice in which the p85β gene
is deleted (
p85
β
−/−
mice). As with the
p85
α
−/−
mice, the
p85
β
−/−
mice showed hypoinsulinemia,
hypoglycemia, and improved insulin sensitivity. At the molecular level,
PI3K activity associated with phosphotyrosine complexes was preserved
despite a 20–30% reduction in the total protein level of the
regulatory subunits. Moreover, insulin-induced activation of AKT was
significantly up-regulated in muscle from the
p85
β
−/−
mice. In addition,
insulin-dependent tyrosine phosphorylation of insulin receptor
substrate-2 was enhanced in the
p85
β
−/−
mice, a phenotype not observed in
the
p85
α
−/−
mice. These results indicate
that in addition to their roles in recruiting the catalytic subunit of
PI3K to the insulin receptor substrate proteins, both p85α and p85β
play negative roles in insulin signaling.
An NO derivative of ursodeoxycholic acid protects against Fas-mediated liver injury by inhibiting caspase activity
Authors: Fiorucci Stefano , Mencarelli Andrea , Palazzetti Barbara , Del Soldato Piero , Morelli Antonio , Ignarro Louis J.
Published: July 2002

Caspases are key mediators in liver inflammation and apoptosis. In the present study we provide evidence that a nitric oxide (NO) derivative of ursodeoxycholic acid (UDCA), NCX-1000 ([2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester]), protects against liver damage in murine models of autoimmune hepatitis induced by i.v. injection of Con A or a Fas agonistic antibody, Jo2. Con A administration causes CD4+T lymphocytes to accumulate in the liver and up-regulates FasL expression, resulting in FasL-mediated cytotoxicity. Cotreating mice with NCX-1000, but not with UDCA, protected against liver damage induced by Con A and Jo2, inhibited IL-1β, IL-18, and IFN-γ release and caspase 3, 8, and 9 activation. Studies on HepG2 cells demonstrated that NCX-1000, but not UDCA, directly prevented multiple caspase activation induced by Jo2. Incubating HepG2 cells with NCX-1000 resulted in intracellular NO formation and a DTT-reversible inhibition of proapoptotic caspases, suggesting that cysteine S-nitrosylation was the main mechanism responsible for caspase inhibition. Collectively, these data suggest that NCX-1000 protects against T helper 1-mediated liver injury by inhibiting both the proapoptotic and the proinflammatory branches of the caspase superfamily.
Increased pollen flow counteracts fragmentation in a tropical dry forest: An example from
Swietenia humilis
Zuccarini
Authors: White G. M. , Boshier D. H. , Powell W.
Published: July 2002

Habitat destruction and the resultant fragmentation of the remaining forest are a common phenomenon in the tropics. Most investigations emphasize the potential dangers of fragmentation in isolating patches of forest and exposing populations to loss of species diversity through founder effects, genetic drift, inbreeding, and restricted gene flow. However, a limited number of studies have shown that gene flow may be extensive in tropical trees, suggesting that it may occur between forest fragments and also “isolated” remnant trees. There is an urgent need to quantify pollen flow within and between forest fragments to test the veracity of such views and determine the genetic value of such fragments for
in situ
conservation. Microsatellite markers are used to genotype individuals of
Swietenia humilis
from a highly fragmented forest mosaic to directly quantify pollen-mediated gene flow. Distances of pollen flow more than 10 times greater than previously reported were detected. Our results show that some tropical angiosperm tree species may be much more adaptable and resilient to habitat destruction and fragmentation than previously considered. The description of many remnant trees as isolated or “living dead” may be more a conditioning of human perception than a true reflection of their potential conservation value.
An NMR approach to structural proteomics
Authors: Yee Adelinda , Chang Xiaoqing , Pineda-Lucena Antonio , Wu Bin , Semesi Anthony , Le Brian , Ramelot Theresa , Lee Gregory M. , Bhattacharyya Sudeepa , Gutierrez Pablo , Denisov Aleksej , Lee Chang-Hun , Cort John R. , Kozlov Guennadi , Liao Jack , Finak Grzegorz , Chen Limin , Wishart David , Lee Weontae , McIntosh Lawrence P. , Gehring Kalle , Kennedy Michael A. , Edwards Aled M. , Arrowsmith Cheryl H.
Published: July 2002

The influx of genomic sequence information has led to the concept of structural proteomics, the determination of protein structures on a genome-wide scale. Here we describe an approach to structural proteomics of small proteins using NMR spectroscopy. Over 500 small proteins from several organisms were cloned, expressed, purified, and evaluated by NMR. Although there was variability among proteomes, overall 20% of these proteins were found to be readily amenable to NMR structure determination. NMR sample preparation was centralized in one facility, and a distributive approach was used for NMR data collection and analysis. Twelve structures are reported here as part of this approach, which allowed us to infer putative functions for several conserved hypothetical proteins.
An unliganded thyroid hormone receptor causes severe neurological dysfunction
Authors: Hashimoto Koshi , Curty Flavio H. , Borges Patricia P. , Lee Charlotte E. , Abel E. Dale , Elmquist Joel K. , Cohen Ronald N. , Wondisford Fredric E.
Published: July 2002

Congenital hypothyroidism and the thyroid hormone (T
3
)
resistance syndrome are associated with severe central nervous system
(CNS) dysfunction. Because thyroid hormones are thought to act
principally by binding to their nuclear receptors (TRs), it is
unexplained why TR knock-out animals are reported to have normal CNS
structure and function. To investigate this discrepancy further, a
T
3
binding mutation was introduced into the mouse TR-β
locus by homologous recombination. Because of this T
3
binding defect, the mutant TR constitutively interacts with corepressor
proteins and mimics the hypothyroid state, regardless of the
circulating thyroid hormone concentrations. Severe abnormalities in
cerebellar development and function and abnormal hippocampal gene
expression and learning were found. These findings demonstrate the
specific and deleterious action of unliganded TR in the brain and
suggest the importance of corepressors bound to TR in the pathogenesis
of hypothyroidism.
Human CD1d–glycolipid tetramers generated byin vitrooxidative refolding chromatography
Authors: Karadimitris Anastasios , Gadola Stephan , Altamirano Myriam , Brown Dave , Woolfson Adrian , Klenerman Paul , Chen Ji-Li , Koezuka Yasuhiko , Roberts Irene A. G. , Price David A. , Dusheiko Geoff , Milstein César , Fersht Alan , Luzzatto Lucio , Cerundolo Vincenzo
Published: July 2002

CD1 molecules are specialized in presenting lipids to T lymphocytes, but identification and isolation of CD1-restricted lipidspecific T cells has been hampered by the lack of reliable and sensitive techniques. We here report the construction of CD1d–glycolipid tetramers from fully denatured human CD1d molecules by using the technique of oxidative refolding chromatography. We demonstrate that chaperone- and foldase-assisted refolding of denatured CD1d molecules and β2-microglobulin in the presence of synthetic lipids is a rapid method for the generation of functional and specific CD1d tetramers, which unlike previously published protocols ensures isolation of CD1d tetramers loaded with a single lipid species. The use of human CD1d–α-galactosylceramide tetramers forex vivostaining of peripheral blood lymphocytes and intrahepatic T cells from patients with viral liver cirrhosis allowed for the first time simultaneous analysis of frequency and specificity of natural killer T cells in human clinical samples. Application of this protocol to other members of the CD1 family will provide powerful tools to investigate lipid-specific T cell immune responses in health and in disease.
Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function
Authors: Wu Xiaosheng , Kasper Lawryn H. , Mantcheva Ralitsa T. , Mantchev George T. , Springett Margaret J. , van Deursen Jan M. A.
Published: July 2002

The NUP98 gene encodes precursor proteins that generate two
nucleoplasmically oriented nucleoporins, NUP98 and NUP96. By using gene
targeting, we have selectively disrupted the murine NUP98 protein,
leaving intact the expression and localization of NUP96. We show that
NUP98 is essential for mouse gastrulation, a developmental stage that
is associated with rapid cell proliferation, but dispensable for basal
cell growth. NUP98−/− cells had an intact nuclear envelope with a
normal number of embedded nuclear pore complexes. Typically,
NUP98-deficient cells contained on average approximately 5-fold more
cytoplasmic annulate lamellae than control cells. We found that a set
of cytoplasmically oriented nucleoporins, including NUP358, NUP214,
NUP88, and p62, assembled inefficiently into nuclear pores of
NUP98−/− cells. Instead, these nucleoporins were prominently
associated with the annulate lamellae. By contrast, a group of
nucleoplasmically oriented nucleoporins, including NUP153, NUP50,
NUP96, and NUP93, had no affinity for annulate lamellae and assembled
normally into nuclear pores. Mutant pores were significantly impaired
in transport receptor-mediated docking of proteins with a nuclear
localization signal or M9 import signal and showed weak nuclear import
of such substrates. In contrast, the ability of mutant pores to import
ribosomal protein L23a and spliceosome protein U1A appeared intact.
These observations show that NUP98 disruption selectively impairs
discrete protein import pathways and support the idea that transport of
distinct import complexes through the nuclear pore complex is mediated
by specific subsets of nucleoporins.
Computational mapping identifies the binding sites of organic solvents on proteins
Authors: Dennis Sheldon , Kortvelyesi Tamas , Vajda Sandor
Published: July 2002

Computational mapping places molecular probes—small molecules or functional groups—on a protein surface to identify the most favorable binding positions. Although x-ray crystallography and NMR show that organic solvents bind to a limited number of sites on a protein, current mapping methods result in hundreds of energy minima and do not reveal why some sites bind molecules with different sizes and polarities. We describe a mapping algorithm that explains the origin of this phenomenon. The algorithm has been applied to hen egg-white lysozyme and to thermolysin, interacting with eight and four different ligands, respectively. In both cases the search finds the consensus site to which all molecules bind, whereas other positions that bind only certain ligands are not necessarily found. The consensus sites are pockets of the active site, lined with partially exposed hydrophobic residues and with a number of polar residues toward the edge. These sites can accommodate each ligand in a number of rotational states, some with a hydrogen bond to one of the nearby donor/acceptor groups. Specific substrates and/or inhibitors of hen egg-white lysozyme and thermolysin interact with the same side chains identified by the mapping, but form several hydrogen bonds and bind in unique orientations.
Protein unfolding: Rigidity lost
Authors: Rader A. J. , Hespenheide Brandon M. , Kuhn Leslie A. , Thorpe M. F.
Published: July 2002

We relate the unfolding of a protein to its loss of structural stability or rigidity. Rigidity and flexibility are well defined concepts in mathematics and physics, with a body of theorems and algorithms that have been applied successfully to materials, allowing the constraints in a network to be related to its deformability. Here we simulate the weakening or dilution of the noncovalent bonds during protein unfolding, and identify the emergence of flexible regions as unfolding proceeds. The transition state is determined from the inflection point in the change in the number of independent bond-rotational degrees of freedom (floppy modes) of the protein as its mean atomic coordination decreases. The first derivative of the fraction of floppy modes as a function of mean coordination is similar to the fraction-folded curve for a protein as a function of denaturant concentration or temperature. The second derivative, a specific heat-like quantity, shows a peak around a mean coordination of 〈r〉 = 2.41 for the 26 diverse proteins we have studied. As the protein denatures, it loses rigidity at the transition state, proceeds to a state where just the initial folding core remains stable, then becomes entirely denatured or flexible. This universal behavior for proteins of diverse architecture, including monomers and oligomers, is analogous to the rigid to floppy phase transition in network glasses. This approach provides a unifying view of the phase transitions of proteins and glasses, and identifies the mean coordination as the relevant structural variable, or reaction coordinate, along the unfolding pathway.
Phosphate backbone neutralization increases duplex DNA flexibility: A model for protein binding
Authors: Okonogi Tamara M. , Alley Stephen C. , Harwood Eric A. , Hopkins Paul B. , Robinson Bruce H.
Published: July 2002

An important component of protein–DNA recognition is the charge neutralization of DNA backbone phosphates and subsequent protein-induced DNA bending. Replacement of phosphates by neutral methylphosphonates has previously been shown to be a model for protein-induced bending. In addition to bending, the neutralization process may change the inherent flexibility of the DNA—a feature never before tested. We have developed a method to measure the differential flexibility of duplex DNA when methylphosphonate substitutions are made and find that the local flexibility is increased up to 40%. These results imply that backbone-neutralization-dependent DNA flexibility augments DNA-binding motifs in protein–DNA recognition processes.
Genetic analysis of the archaeon
Methanosarcina barkeri
Fusaro reveals a central role for Ech hydrogenase and ferredoxin in methanogenesis and carbon fixation
Authors: Meuer Jörn , Kuettner H. Craig , Zhang Jun Kai , Hedderich Reiner , Metcalf William W.
Published: July 2002

Ech hydrogenase (Ech) from the methanogenic archaeon
Methanosarcina barkeri
catalyzes the reversible reduction of ferredoxin by H
2
and is a member of a distinct group of membrane-bound [NiFe] hydrogenases with sequence similarity to energy-conserving NADH:quinone oxidoreductase (complex I). To elucidate the physiological role(s) of Ech a mutant lacking this enzyme was constructed. The mutant was unable to grow on methanol/H
2
/CO
2
, H
2
/CO
2
, or acetate as carbon and energy sources but showed wild-type growth rates with methanol as sole substrate. Addition of pyruvate to the growth medium restored growth on methanol/H
2
/CO
2
but not on H
2
/CO
2
or acetate. Results obtained from growth experiments, cell suspension experiments, and enzyme activity measurements in cell extracts provide compelling evidence for essential functions of Ech and a 2[4Fe-4S] ferredoxin in the metabolism of
M. barkeri
. The following conclusions were made. (
i
) In acetoclastic methanogenesis, Ech catalyzes H
2
formation from reduced ferredoxin, generated by the oxidation of the carbonyl group of acetate to CO
2
. (
ii
) Under autotrophic growth conditions, the enzyme catalyzes the energetically unfavorable reduction of ferredoxin by H
2
, most probably driven by reversed electron transport, and the reduced ferredoxin thus generated functions as low potential electron donor for the synthesis of pyruvate in an anabolic pathway. (
iii
) Reduced ferredoxin in addition provides the reducing equivalents for the first step of methanogenesis from H
2
/CO
2
, the reduction of CO
2
to formylmethanofuran. Thus,
in vivo
genetic analysis has led to the identification of the electron donor of this key initial step of methanogenesis.
Radial and longitudinal diffusion of myoglobin in single living heart and skeletal muscle cells
Authors: Papadopoulos Simon , Endeward Volker , Revesz-Walker Brigitta , Jürgens Klaus D. , Gros Gerolf
Published: July 2002

We have used a fluorescence recovery after photobleaching
(FRAP) technique to measure radial diffusion of myoglobin and other
proteins in single skeletal and cardiac muscle cells. We compare the
radial diffusivities,
D
r
(i.e., diffusion
perpendicular to the long fiber axis), with longitudinal ones,
D
l
(i.e., parallel to the long fiber axis),
both measured by the same technique, for myoglobin (17 kDa),
lactalbumin (14 kDa), and ovalbumin (45 kDa). At 22°C,
D
l
for myoglobin is 1.2 ×
10
−7
cm
2
/s in soleus fibers
and 1.1 × 10
−7
cm
2
/s
in cardiomyocytes.
D
l
for lactalbumin is
similar in both cell types.
D
r
for myoglobin
is 1.2 × 10
−7
cm
2
/s in
soleus fibers and 1.1 × 10
−7
cm
2
/s in cardiomyocytes and, again,
similar for lactalbumin.
D
l
and
D
r
for ovalbumin are 0.5 ×
10
−7
cm
2
/s. In the case of
myoglobin, both
D
l
and
D
r
at 37°C are about 80% higher than at
22°C. We conclude that intracellular diffusivity of myoglobin and
other proteins (
i
) is very low in striated muscle cells,
≈1/10 of the value in dilute protein solution, (
ii
)
is not markedly different in longitudinal and radial direction, and
(
iii
) is identical in heart and skeletal muscle. A Krogh
cylinder model calculation holding for steady-state tissue oxygenation
predicts that, based on these myoglobin diffusivities,
myoglobin-facilitated oxygen diffusion contributes 4% to the overall
intracellular oxygen transport of maximally exercising skeletal muscle
and less than 2% to that of heart under conditions of high work load.