bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of swirl on jets and wakes: Linear instability of the Rankine vortex with axial flow
Authors: Loiseleux T. , Chomaz J. M. , Huerre P.
Published: July 2002

The effect of swirl on jets and wakes is investigated by analyzing the inviscid spatiotemporal instability of the Rankine vortex with superimposed plug flow axial velocity profile. The linear dispersion relation is derived analytically as a function of two nondimensional control parameters: the swirl ratio S and the external axial flow parameter a (a>−0.5 for jets, a<−0.5 for wakes). For each azimuthal wave number m, there exists a single unstable Kelvin–Helmholtz mode and an infinite number of neutrally stable inertial waveguide modes. Swirl decreases the temporal growth rate of the axisymmetric Kelvin–Helmholtz mode (m=0), which nonetheless remains unstable for all axial wave numbers. For helical modes (m≠0), small amounts of swirl lead to the widespread occurrence of direct resonances between the unstable Kelvin–Helmholtz mode and the inertial waveguide modes. Such interactions generate, in the low wave number range, neutrally stable wave number bands separated by bubbles of instability. As S increases above a critical value, all bubbles merge to give rise to unstable wave numbers throughout, but the growth rate envelope decreases continuously with increasing swirl. In the high wave number range, negative helical mode growth rates are enhanced for small swirl and decrease continuously for large swirl, while positive helical mode growth rates monotonically decrease with increasing swirl. For a given positive swirl, negative modes are more unstable than their positive counterparts, although their growth rates may not necessarily be larger than in the nonrotating case. The absolute/convective nature of the instability in swirling jets and wakes is determined in an a−S control parameter plane by numerical implementation of the Briggs–Bers criterion. In the absence of swirl, jets (a>−0.5) become absolutely unstable (AI) to the axisymmetric mode m=0 only for a sufficiently large external axial counterflow a<−0.15. AI is found to be significantly enhanced by swirl: for S>1.61, AI occurs, even for coflowing jets (a>0). As S is gradually increased, the transitional mode to AI successively becomes m=0, −1, −2, −3, etc. In the absence of swirl, wakes (a<−0.5) become absolutely unstable to the bending modes m=±1 only for sufficiently large counterflow 1+a>0.091. For S>0.47, AI occurs even for coflowing wakes (a<−1) and, as S increases, the transitional mode to AI successively becomes m=−1, −2, −3, etc. This instability analysis is found to provide a preliminary estimate of the critical Rossby number for the onset of vortex breakdown: for zero external axial flow jets (a=0), absolute/convective transition first takes place at a Rossby number Ro≡S−1∼0.62, which very favorably compares with available experimental and numerical threshold values for vortex breakdown onset.
Experimental analysis of intermittent coherent structures in the near field of a high Re turbulent jet flow
Authors: Camussi R. , Guj G.
Published: July 2002

Experimental data obtained in the near region of a turbulent jet flow (from x/D=0 up to x/D=19, where D is the jet diameter and x is the axial coordinate) are processed through wavelet decomposition. A wavelet based technique for coherent structures identification is applied to the longitudinal and transverse velocity data series obtained by X probe hot wire anemometry measurements. This methodology permits the evolution with x of the time signature of coherent structures to be analyzed. The statistics of the local turbulent energy magnitude is also discussed and the temporal dynamics is studied by the analysis of the time of appearance of the most energetic structures evolving with x/D.
Two-dimensional magnetic field evolution measurements and plasma flow speed estimates from the coaxial thruster experiment
Authors: Black D. C. , Mayo R. M. , Gerwin R. A. , Schoenberg K. F. , Scheuer J. T. , Hoyt R. P. , Henins I.
Published: July 2002

Local, time-dependent magnetic field measurements have been made in the Los Alamos coaxial thruster experiment (CTX) [C. W. Barnes et al., Phys. Fluids B 2, 1871 (1990); J. C. Fernández et al., Nucl. Fusion 28, 1555 (1988)] using a 24 coil magnetic probe array (eight spatial positions, three axis probes). The CTX is a magnetized, coaxial plasma gun presently being used to investigate the viability of high pulsed power plasma thrusters for advanced electric propulsion. Previous efforts on this device have indicated that high pulsed power plasma guns are attractive candidates for advanced propulsion that employ ideal magnetohydrodynamic (MHD) plasma stream flow through self-formed magnetic nozzles. Indirect evidence of magnetic nozzle formation was obtained from plasma gun performance and measurements of directed axial velocities up to vz∼107 cm/s. The purpose of this work is to make direct measurement of the time evolving magnetic field topology. The intent is to both identify that applied magnetic field distortion by the highly conductive plasma is occurring, and to provide insight into the details of discharge evolution. Data from a magnetic fluctuation probe array have been used to investigate the details of applied magnetic field deformation through the reconstruction of time-dependent flux profiles. Experimentally observed magnetic field line distortion has been compared to that predicted by a simple one-dimensional (1-D) model of the discharge channel. Such a comparison is utilized to estimate the axial plasma velocity in the thruster. Velocities determined in this manner are in approximate agreement with the predicted self-field magnetosonic speed and those measured by a time-of-flight spectrometer.
Various divertor biasing configurations and improved divertor performance with biasing on Tokamak de Varennes (TdeV)*
Authors: Décoste R. , Lachambre J.-L. , Abel G. , Boileau A. , Boucher C. , Côte A. , Fall T. , Gauvreau J.-L. , Gregory B. C. , Haddad E. , Janicki C. , Liu-Hinz C. , Mai H. H. , Martin F. , Michaud D. , Richard N. , Ross G. , Sarkissian A. , Stansfield B. L. , Terreault B. , Zuzak W.
Published: July 2002

Electrically insulated divertor plates are used on TdeV (Tokamak de Varennes) [18th EPS Conference on Controlled Fusion and Plasma Physics Berlin (European Physical Society, Petit-Lancy, 1991), Vol. 15C, Part I, pp. 1–141] to produce various biasing configurations, which can be decomposed into two basic modes. Plasma biasing, with a radial electric field Er in the scrape-off layer (SOL), is most promising for divertor applications. The Er field is produced with a particular divertor plate geometry, causing a nonambipolar radial current and a particle flow in the Er×BT direction, toward one of the divertors (the active divertor). The pressure and impurity retention in the active divertor are shown, in the Ohmic regime, to be strongly increased by biasing. He exhaust through this divertor is increased by a factor of almost 3 with modest biasing voltages and currents scalable to larger devices. Biasing also modifies the power repartition between the divertors, with the active divertor also receiving a larger fraction of the power.
Theory of magnetohydrodynamic instabilities excited by energetic particles in tokamaks*
Authors: Chen Liu
Published: July 2002

The resonant excitations of high-n magnetohydrodynamic instabilities by the energetic ions/alpha particles in tokamaks are theoretically analyzed. Here, n is the toroidal mode number. The magnetohydrodynamic eigenmodes, typically, consist of two-scale structures; one corresponds to the singular (‘‘inertial’’) region and the other the regular (ideal) region. Due to the finite-size orbits, the energetic particle contributions in the singular region are suppressed. Analytical dispersion relations can be derived via the asymptotic matching analysis. The dispersion relations have the generic form of the ‘‘fishbone’’ dispersion relation [Phys. Rev. Lett. 52, 1122 (1984)] and demonstrate, in particular, the existence of two types of modes; that is, the discrete gap mode and the energetic-particle continuum mode. Specific expressions are given for both the kinetic ballooning modes and the toroidal Alfvén modes.
Toroidal gyro-Landau fluid model turbulence simulations in a nonlinear ballooning mode representation with radial modes
Authors: Waltz R. E. , Kerbel G. D. , Milovich J.
Published: July 2002

The method of Hammett and Perkins [Phys. Rev. Lett. 64, 3019 (1990)] to model Landau damping has been recently applied to the moments of the gyrokinetic equation with curvature drift by Waltz, Dominguez, and Hammett [Phys. Fluids B 4, 3138 (1992)]. The higher moments are truncated in terms of the lower moments (density, parallel velocity, and parallel and perpendicular pressure) by modeling the deviation from a perturbed Maxwellian to fit the kinetic response function at all values of the kinetic parameters: k∥vth/ω, b=(k⊥ρ)2/2, and ωD/ω. Here the resulting gyro-Landau fluid equations are applied to the simulation of ion temperature gradient (ITG) mode turbulence in toroidal geometry using a novel three-dimensional (3-D) nonlinear ballooning mode representation. The representation is a Fourier transform of a field line following basis (ky′,kx′,z′) with periodicity in toroidal and poloidal angles. Particular emphasis is given to the role of nonlinearly generated n=0 (ky′ = 0, kx′ ≠ 0) ‘‘radial modes’’ in stabilizing the transport from the finite-n ITG ballooning modes. Detailing the parametric dependence of toroidal ITG turbulence is a key result.
Density measurements in the edge, divertor and X-point regions of Alcator C-Mod from Balmer series emission
Authors: Welch B. L. , Griem H. R. , Terry J. , Kurz C. , LaBombard B. , Lipschultz B. , Marmar E. , McCracken G.
Published: July 2002

The electron density in the edge, divertor and X-point regions of Alcator C-Mod [Proceedings of the IEEE 13th Symposium on Fusion Engineering (Institute of Electrical and Electronic Engineers, New York, 1990), Vol. 1, p. 13] has been measured using the Stark broadening of high-n (n=8 through 11) transitions of the Balmer series of deuterium. These measurements have been made during typical single null, diverted operation and during gas-puffing through capillaries located within the first wall and divertor. Electron densities up to 1.6×1021 m−3 have been measured in the X-point region and slightly lower densities (5−7×1020 m−3) have been measured in the divertor and edge regions. These results are factors of 2 to 5 larger than the density measurements from the CO2 laser interferometer system in the main chamber (3×1020 m−3) and comparable with probe measurements in the divertor. The ratios of the widths of adjacent lines within the Balmer series have been compared with ratios calculated for the Stark broadening of these lines. These transitions can be used to measure electron densities from 3×1019 to 2×1021 m−3 with a modest resolution spectrograph [(Δλinst=1 Å full width at half maximum)].
Rethermalization of a field-reversed configuration plasma in translation experiments
Authors: Himura Haruhiko , Okada Shigefumi , Sugimoto Satoshi , Goto Seiichi
Published: July 2002

A translation experiment of field-reversed configuration (FRC) plasma is performed on the FIX machine [Shiokawa and Goto, Phys. Fluids B 5, 534 (1993)]. The translated FRC bounces between magnetic mirror fields at both ends of a confinement region. The plasma loses some of its axial kinetic energy when it is reflected by the magnetic mirror field, and eventually settles down in the confinement region. In this reflection process, the plasma temperature rises significantly. Such plasma rethermalization has been observed in OCT-L1 experiments [Ito et al., Phys. Fluids 30, 168 (1987)], but rarely in FRX-C/T experiments [Rej et al., Phys. Fluids 29, 852 (1986)]. It is found that the rethermalization depends on the relation between the plasma temperature and the translation velocity. The rethermalization occurs only in the case where the translation velocity exceeds the sound velocity. This result implies the rethermalization is caused by a shock wave induced within the FRC when the plasma is reflected by the magnetic mirror field.
Studies of impurity mode and ion temperature gradient mode in toroidal plasmas
Authors: Dong J. Q. , Horton W.
Published: July 2002

The impurity mode and ηi mode driven by impurity ions with outwardly peaked density profiles, near the boundary of tokamak plasmas, and the ion temperature gradient, respectively, are studied in high-temperature toroidal plasmas. The gyrokinetic theory is applied and finite Larmor radius effects of both hydrogenic and impurity ions are included. It is found that the impurity mode is enhanced by the ion temperature gradient. In addition, the impurity ions with outwardly peaked density profiles are demonstrated to have destabilizing effects on the ηi mode. These two modes are strongly coupled to each other so that it is impossible to distinguish between them when both the driving mechanisms are strong enough to drive the corresponding mode unstable independently. The correlation of the results with nonlinear simulations and the experimental observations are discussed.
Coupling of ηi and trapped electron modes in plasmas with negative magnetic shear
Authors: Dong J. Q. , Mahajan S. M. , Horton W.
Published: July 2002

In toroidal collisionless plasmas, the ion temperature gradient (ITG or ηi) and the trapped electron (TE) modes are shown to be weakly (strongly) coupled when both the temperature gradients and the driving mechanism of the trapped electrons are moderate to strong (weak but finite). In the regime of strong coupling, there is a single hybrid mode, unstable for all ηi in plasmas with positive magnetic shear. For the weak coupling case, two independent unstable modes, one in the ion and the other in the electron diamagnetic direction, are found to coexist. In either situation, the negative magnetic shear exerts a strong stabilizing influence; the stabilizing effect is considerably enhanced by the presence of trapped particles. It is predicted that for a given set of plasma parameters, it will be much harder to simultaneously excite the two modes in a plasma with negative shear. The results of this study are significant for tokamak experiments.
Sheath criterion and boundary conditions for an electrostatic sheath
Authors: Chen X. P.
Published: July 2002

The effect of collisionality of ions on the formation of a positive sheath is investigated using a two-fluid model. It is the definition of the sheath edge that determines the sheath criterion. Bohm’s sheath criterion is based on the collisionless sheath and a quasineutral presheath. When collisions of ions in the sheath or finite space charge of presheath are taken into account, a sheath criterion can also be obtained based on the boundary conditions chosen at the sheath edge.
Penetration of a compressible magnetized plasma object into a low beta target plasma
Authors: Hwang D. Q. , Ryutova M. , McLean H.
Published: July 2002

The effects of the shape and compressibility of a perfectly conducting spheromaklike compact toroid (SCT) propagating into a low beta plasma have been studied. Simple tools that allow one to identify conditions for the optimum penetration of the SCT into the low beta target plasma have been developed. The main results obtained are (1) squeezed (prolate) SCT’s penetrate more easily; (2) including SCT compressibility reduces injection power requirement, and (3) there exists a broad parameter range where the SCT injection can maintain tokamak particle inventory while simultaneously reducing external auxiliary heating requirements.
Analysis of perturbed magnetic fields via construction of nearby integrable fields
Authors: Hudson S. R. , Dewar R. L.
Published: July 2002

For a given nonintegrable toroidal magnetic field, a nearby integrable magnetic field is constructed from quadratic-flux minimizing surfaces. A new mathematical definition and derivation of quadratic-flux minimizing surfaces, which directly exploits the analogy between toroidal magnetic fields and 112 degree of freedom Hamiltonian systems, is given. The width and phase of magnetic islands (calculated from the shear of the integrable field and the magnitude and phase of the perturbation harmonics) are in excellent agreement with detailed Poincaré plots.
Dust-acoustic waves in strongly coupled plasmas with variable dust charge
Authors: Xie B. S. , Yu M. Y.
Published: July 2002

A generalized theory of dust-acoustic waves in strongly coupled dusty plasmas containing variable-charge dusts or impurities is given. Relaxation processes associated with the strong coupling, as well as dust-charge variation, are taken into account. It is shown that the dispersion and damping properties of the waves are strongly affected by dust-dust correlation, dust charging and viscoelastic relaxations, and dust-neutral collisions. Multiple transitions between positive to negative dispersions are also found and discussed.
Antiphase boundaries in epitaxially grown β-SiC
Authors: Pirouz P. , Chorey C. M. , Powell J. A.
Published: July 2002

When the surface of β-SiC, grown epitaxially on (001) silicon by chemical vapor deposition, is chemically etched, boundaries appear which may be observed by optical or scanning electron microscopy. Examination by plan-view and cross-sectional transmission electron microscopy shows boundaries in the film which exhibit line or fringe contrast. Convergent beam electron diffraction has been used to show that these boundaries separate domains that are in an antiphase relationship to each other. A model is presented which discusses the formation of these domains from independent nucleation on a stepped substrate surface.
Exact determination of superlattice structures by small-angle x-ray diffraction method
Authors: Sugawara M. , Kondo M. , Yamazaki S. , Nakajima K.
Published: July 2002

The structure of In1−xGaxAsyP1−y/InP superlattices (x=0.27 and y=0.60) is investigated by small-angle x-ray diffraction method. The interference peaks due to the superlattice structure were clearly observed up to the 6th order. The period of the superlattice was determined from the angular positions of the peaks using the modified Bragg’s law. By analyzing the diffraction patterns of the first and the secondary peaks according to the optical multilayer theory, the thickness of each component (In1−xGaxAsyP1−y and InP) was uniquely determined within an error of ±1 Å. This method can be used to determine any type of superlattice structure.
Experimental confirmation of a sum rule for room-temperature electroabsorption in GaAs-AlGaAs multiple quantum well structures
Authors: Whitehead M. , Parry G. , Woodbridge K. , Dobson P. J. , Duggan G.
Published: July 2002

Measurements of the electric field dependence of room-temperature photocurrent in a GaAs-A10.4Ga0.6As multiple quantum well p-i-n diode have been carried out in the wavelength range 650–920 nm. Calculations of the field dependence of absorption from the photocurrent spectra show that the recently derived sum rule for electroabsorption in quantum wells holds to within 0.3%, for electric fields as high as 2×105 V/cm, provided that full account is taken of changes in absorption across the entire spectral region.
High throughput DNA sequencing with a microfabricated 96-lane capillary array electrophoresis bioprocessor
Authors: Paegel Brian M. , Emrich Charles A. , Wedemayer Gary J. , Scherer James R. , Mathies Richard A.
Published: July 2002

High throughput DNA sequencing has been performed by using a microfabricated 96-channel radial capillary array electrophoresis (μCAE) microchannel plate detected by a 4-color rotary confocal fluorescence scanner. The microchannel plate features a novel injector for uniform sieving matrix loading as well as high resolution, tapered turns that provide an effective separation length of 15.9 cm on a compact 150-mm diameter wafer. Expanded common buffer chambers for the cathode, anode, and waste reservoirs are used to simplify electrode addressing and to counteract buffering capacity depletion arising from the high electrophoretic current. DNA sequencing data from 95 successful lanes out of 96 lanes run in parallel were batch-processed with
basefinder
, producing an average read length of 430 bp (phred q ≥ 20). Phred quality values were found to exceed 40 (0.01% probability of incorrectly calling a base) for over 80% of the read length. The μCAE system demonstrated here produces sequencing data at a rate of 1.7 kbp/min, a 5-fold increase over current commercial capillary array electrophoresis technology. Additionally, this system permits lower reagent volumes and lower sample concentrations, and it presents numerous possibilities for integrated sample preparation and handling. The unique capabilities of μCAE technology should make it the next generation, high performance DNA sequencing platform.
A genomic approach to gene fusion technology
Authors: Van Dyk Tina K. , Wei Yan , Hanafey Michael K. , Dolan Maureen , Reeve Mary Jane G. , Rafalski J. Antoni , Rothman-Denes Lucia B. , LaRossa Robert A.
Published: July 2002

Gene expression profiling provides powerful analyses of
transcriptional responses to cellular perturbation. In contrast to DNA
array-based methods, reporter gene technology has been underused for
this application. Here we describe a genomewide, genome-registered
collection of
Escherichia coli
bioluminescent reporter
gene fusions. DNA sequences from plasmid-borne, random fusions of
E. coli
chromosomal DNA to a
Photorhabdus
luminescens luxCDABE
reporter allowed precise mapping of each
fusion. The utility of this collection covering about 30% of the
transcriptional units was tested by analyzing individual fusions
representative of heat shock, SOS, OxyR, SoxRS, and
cya/crp
stress-responsive regulons. Each fusion strain
responded as anticipated to environmental conditions known to activate
the corresponding regulatory circuit. Thus, the collection mirrors
E. coli
's transcriptional wiring diagram. This
genomewide collection of gene fusions provides an independent test of
results from other gene expression analyses. Accordingly, a DNA
microarray-based analysis of mitomycin C-treated
E. coli
indicated elevated expression of expected and unanticipated genes.
Selected
luxCDABE
fusions corresponding to these
up-regulated genes were used to confirm or contradict the DNA
microarray results. The power of partnering gene fusion and DNA
microarray technology to discover promoters and define operons was
demonstrated when data from both suggested that a cluster of 20 genes
encoding production of type I extracellular polysaccharide in
E.
coli
form a single operon.
Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells
Authors: Wu S. Vincent , Rozengurt Nora , Yang Moon , Young Steven H. , Sinnett-Smith James , Rozengurt Enrique
Published: July 2002

Although a role for the gastric and intestinal mucosa in molecular sensing has been known for decades, the initial molecular recognition events that sense the chemical composition of the luminal contents has remained elusive. Here we identified putative taste receptor gene transcripts in the gastrointestinal tract. Our results, using reverse transcriptase–PCR, demonstrate the presence of transcripts corresponding to multiple members of the T2R family of bitter taste receptors in the antral and fundic gastric mucosa as well as in the lining of the duodenum. In addition, cDNA clones of T2R receptors were detected in a rat gastric endocrine cell cDNA library, suggesting that these receptors are expressed, at least partly, in enteroendocrine cells. Accordingly, expression of multiple T2R receptors also was found in STC-1 cells, an enteroendocrine cell line. The expression of α subunits of G proteins implicated in intracellular taste signal transduction, namely Gα
gust
, and Gα
t
-
2
, also was demonstrated in the gastrointestinal mucosa as well as in STC-1 cells, as revealed by reverse transcriptase–PCR and DNA sequencing, immunohistochemistry, and Western blotting. Furthermore, addition of compounds widely used in bitter taste signaling (e.g., denatonium, phenylthiocarbamide, 6-n-propil-2-thiouracil, and cycloheximide) to STC-1 cells promoted a rapid increase in intracellular Ca
2+
concentration. These results demonstrate the expression of bitter taste receptors of the T2R family in the mouse and rat gastrointestinal tract.
Positive Darwinian selection drives the evolution of several female reproductive proteins in mammals
Authors: Swanson Willie J. , Yang Ziheng , Wolfner Mariana F. , Aquadro Charles F.
Published: July 2002

Rapid evolution driven by positive Darwinian selection is a
recurrent theme in male reproductive protein evolution. In contrast,
positive selection has never been demonstrated for female reproductive
proteins. Here, we perform phylogeny-based tests on three female
mammalian fertilization proteins and demonstrate positive selection
promoting their divergence. Two of these female fertilization proteins,
the zona pellucida glycoproteins ZP2 and ZP3, are part of the mammalian
egg coat. Several sites identified in ZP3 as likely to be under
positive selection are located in a region previously demonstrated to
be involved in species-specific sperm-egg interaction, suggesting the
selective pressure is related to male-female interaction. The results
provide long-sought evidence for two evolutionary hypotheses: sperm
competition and sexual conflict.
Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury
Authors: Kwon Brian K. , Liu Jie , Messerer Corrie , Kobayashi Nao R. , McGraw John , Oschipok Loren , Tetzlaff Wolfram
Published: July 2002

Scientific interest to find a treatment for spinal cord injuries has led to the development of numerous experimental strategies to promote axonal regeneration across the spinal cord injury site. Although these strategies have been developed in acute injury paradigms and hold promise for individuals with spinal cord injuries in the future, little is known about their applicability for the vast majority of paralyzed individuals whose injury occurred long ago and who are considered to have a chronic injury. Some studies have shown that the effectiveness of these approaches diminishes dramatically within weeks after injury. Here we investigated the regenerative capacity of rat rubrospinal neurons whose axons were cut in the cervical spinal cord 1 year before. Contrary to earlier reports, we found that rubrospinal neurons do not die after axotomy but, rather, they undergo massive atrophy that can be reversed by applying brain-derived neurotrophic factor to the cell bodies in the midbrain. This administration of neurotrophic factor to the cell body resulted in increased expression of growth-associated protein-43 and Tα1 tubulin, genes thought to be related to axonal regeneration. This treatment promoted the regeneration of these chronically injured rubrospinal axons into peripheral nerve transplants engrafted at the spinal cord injury site. This outcome is a demonstration of the regenerative capacity of spinal cord projection neurons a full year after axotomy.
Increasedin vivoapoptosis in cells lacking mitochondrial DNA gene expression
Authors: Wang Jianming , Silva José P. , Gustafsson Claes M. , Rustin Pierre , Larsson Nils-Göran
Published: July 2002

We have attempted to determine whether loss of mtDNA and respiratory chain function result in apoptosisin vivo. Apoptosis was studied in embryos with homozygous disruption of the mitochondrial transcription factor A gene (Tfam) and tissue-specificTfamknockout animals with severe respiratory chain deficiency in the heart. We found massive apoptosis inTfamknockout embryos at embryonic day (E) 9.5 and increased apoptosis in the heart of the tissue-specificTfamknockouts. Furthermore, mtDNA-less (ρ0) cell lines were susceptible to apoptosis induced by different stimuliin vitro. The data presented here providein vivoevidence that respiratory chain deficiency predisposes cells to apoptosis, contrary to previous assumptions based onin vitrostudies of cultured cells. These results suggest that increased apoptosis is a pathogenic event in human mtDNA mutation disorders. The finding that respiratory chain deficiency is associated with increasedin vivoapoptosis may have important therapeutic implications for human disease. Respiratory chain deficiency and cell loss and/or apoptosis have been associated with neurodegeneration, heart failure, diabetes mellitus, and aging. Furthermore, chemotherapy and radiation treatment of cancer are intended to induce apoptosis in tumor cells. It would therefore be of interest to determine whether manipulation of respiratory chain function can be used to inhibit or enhance apoptosis in these conditions.
Conflicting levels of selection in the accumulation of mitochondrial defects in
Saccharomyces
cerevisiae
Authors: Taylor Douglas R. , Zeyl Clifford , Cooke Erin
Published: July 2002

The somatic accumulation of defective mitochondria causes human degenerative syndromes, senescence in fungi, and male sterility in plants. These diverse phenomena may result from conflicts between natural selection at different levels of organization. Such conflicts are fundamental to the evolution of cooperating groups, from cells to populations. We present a model in which defective mitochondrial genomes accumulate because of a within-cell replication advantage when among-cell selection for efficient respiration is relaxed. We tested the model by using experimental populations of the yeast
Saccharomyces cerevisiae
. We constructed yeast strains that were heteroplasmic for mitochondrial mutations that destroy the ability to respire (the petite phenotype) and followed the accumulation of mitochondrial defects in cultures with different effective population sizes. As predicted by the model, the inability to respire evolved only in small populations of
S. cerevisiae
, where among-cell selection favoring cells that can respire was reduced relative to within-cell selection favoring parasitic mitochondria. In a control experiment, mitochondrial point mutations that confer resistance to chloramphenicol showed no tendency to change in frequency under any culture conditions. The accumulation of some mitochondrial defects is therefore an evolutionary process, involving multiple levels of selection. The relative intensities of within- and among-cell selection may also explain the tissue specificity of human mitochondrial defects.
A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: Anxiolytic profile in the rat
Authors: Jenck François , Wichmann Juergen , Dautzenberg Frank M. , Moreau Jean-Luc , Ouagazzal Abdel M. , Martin James R. , Lundstrom Kenneth , Cesura Andrea M. , Poli Sonia M. , Roever Stephan , Kolczewski Sabine , Adam Geo , Kilpatrick Gavin
Published: July 2002

The biochemical and behavioral effects of a nonpeptidic, selective, and brain-penetrant agonist at the ORL1 receptor are reported herein. This low molecular weight compound {(1
S
,3a
S
)-8- (2,3,3a,4,5,6-hexahydro-1
H
-phenalen-1-yl)-1-phenyl-1,3,8-triaza- spiro[4.5]decan-4-one} has high affinity for recombinant human ORL1 receptors and has 100-fold selectivity for ORL1 over other members of the opioid receptor family. It is a full agonist at these receptors and elicits dose-dependent anxiolytic-like effects in a set of validated models of distinct types of anxiety states in the rat (i.e., elevated plus-maze, fear-potentiated startle, and operant conflict). When given systemically, the compound has an efficacy and potency comparable to those of a benzodiazepine anxiolytic such as alprazolam or diazepam. However, this compound is differentiated from a classical benzodiazepine anxiolytic by a lack of efficient anti-panic-like activity, absence of anticonvulsant properties, and lack of effects on motor performance and cognitive function at anxiolytic doses (0.3 to 3 mg/kg i.p.). No significant change in intracranial self-stimulation performance and pain reactivity was observed in this dose range. Higher doses of this compound (≥10 mg/kg) induced disruption in rat behavior. These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphanin FQ/nociceptin in adaptive behavioral fear responses to stress.
Naturally variant autosomal and sex-linked loci determine the severity of iron overload in β2-microglobulin-deficient mice
Authors: Sproule Thomas J. , Jazwinska Elizabeth C. , Britton Robert S. , Bacon Bruce R. , Fleming Robert E. , Sly William S. , Roopenian Derry C.
Published: July 2002

Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class I heavy chain paralogue geneHFEhas been found to be a primary cause of HH. However, many individuals homozygous for the defective allele ofHFEdo not develop iron overload, raising the possibility that genetic variation in modifier loci contributes to the HH phenotype. Mice deficient in the product of the β2-microglobulin (β2M) class I light chain fail to express HFE and other MHC class I family proteins, and they have been found to manifest many characteristics of the HH phenotype. To determine whether natural genetic variation plays a role in controlling iron overload, we performed classical genetic analysis of the iron-loading phenotype in β2M-deficient mice in the context of different genetic backgrounds. Strain background was found to be a major determinant in iron loading. Sex played a role that was less than that of strain background but still significant. Resistance and susceptibility to iron overload segregated as complex genetic traits in F1and back-cross progeny. These results suggest the existence of naturally variant autosomal and Y chromosome-linked modifier loci that, in the context of mice genetically predisposed by virtue of a β2M deficiency, can profoundly influence the severity of iron loading. These results thus provide a genetic explanation for some of the variability of the HH phenotype.
Evolution of genome–phenome diversity under environmental stress
Authors: Nevo Eviatar
Published: July 2002

The genomic era revolutionized evolutionary biology. The enigma of genotypic-phenotypic diversity and biodiversity evolution of genes, genomes, phenomes, and biomes, reviewed here, was central in the research program of the Institute of Evolution, University of Haifa, since 1975. We explored the following questions. (i) How much of the genomic and phenomic diversity in nature is adaptive and processed by natural selection? (ii) What is the origin and evolution of adaptation and speciation processes under spatiotemporal variables and stressful macrogeographic and microgeographic environments? We advanced ecological genetics into ecological genomics and analyzed globally ecological, demographic, and life history variables in 1,200 diverse species across life, thousands of populations, and tens of thousands of individuals tested mostly for allozyme and partly for DNA diversity. Likewise, we tested thermal, chemical, climatic, and biotic stresses in several model organisms. Recently, we introduced genetic maps and quantitative trait loci to elucidate the genetic basis of adaptation and speciation. The genome–phenome holistic model was deciphered by the global regressive, progressive, and convergent evolution of subterranean mammals. Our results indicate abundant genotypic and phenotypic diversity in nature. The organization and evolution of molecular and organismal diversity in nature at global, regional, and local scales are nonrandom and structured; display regularities across life; and are positively correlated with, and partly predictable by, abiotic and biotic environmental heterogeneity and stress. Biodiversity evolution, even in small isolated populations, is primarily driven by natural selection, including diversifying, balancing, cyclical, and purifying selective regimes, interacting with, but ultimately overriding, the effects of mutation, migration, and stochasticity.
Adenosylcobalamin inhibits ribosome binding to
btuB
RNA
Authors: Nou Xiangwu , Kadner Robert J.
Published: July 2002

Expression of the
btuB
gene encoding the outer membrane cobalamin transporter in
Escherichia coli
is strongly reduced on growth with cobalamins. Previous studies have shown that this regulation occurs in response to adenosylcobalamin (Ado-Cbl) and operates primarily at the translational level. Changes in the level and stability of
btuB
RNA are consequences of the modulated translation initiation. To examine how Ado-Cbl affects translation, the binding of
E. coli
30S ribosomal subunits to
btuB
RNA was investigated by using a primer extension inhibition assay. Ribosome binding to
btuB
RNA was much less efficient than to other RNAs and was preferentially lost when the ribosomes were subjected to a high-salt wash. Ribosome binding to
btuB
RNA was inhibited by Ado-Cbl but not by cyanocobalamin, with half-maximal inhibition around 0.3 μM Ado-Cbl. Ribosome-binding activity was increased or decreased by mutations in the
btuB
leader region, which affected two predicted RNA hairpins and altered expression of
btuB-lacZ
reporters. Finally, the presence of Ado-Cbl elicited formation of a single primer extension-inhibition product with the same specificity and Cbl-concentration dependence as the inhibition of ribosome binding. These results indicate that
btuB
expression is controlled by the specific binding of Ado-Cbl to
btuB
RNA, which then affects access to its ribosome-binding sequence.
Acute systemic inflammation up-regulates secretory sphingomyelinase
in vivo
: A possible link between inflammatory cytokines and atherogenesis
Authors: Wong Ma-Li , Xie Boxun , Beatini Nan , Phu Phan , Marathe Sudhir , Johns Anthony , Gold Philip W. , Hirsch Emmet , Williams Kevin Jon , Licinio Julio , Tabas Ira
Published: July 2002

Inflammation plays a critical role in atherogenesis, yet the mediators linking inflammation to specific atherogenic processes remain to be elucidated. One such mediator may be secretory sphingomyelinase (S-SMase), a product of the acid sphingomyelinase gene. The secretion of S-SMase by cultured endothelial cells is induced by inflammatory cytokines, and
in vivo
data have implicated S-SMase in subendothelial lipoprotein aggregation, macrophage foam cell formation, and possibly other atherogenic processes. Thus, the goal of this study was to seek evidence for S-SMase regulation
in vivo
during a physiologically relevant inflammatory response. First, wild-type mice were injected with saline or lipopolysaccharide (LPS) as a model of acute systemic inflammation. Serum S-SMase activity 3 h postinjection was increased 2- to 2.5-fold by LPS (
P
< 0.01). To determine the role of IL-1 in the LPS response, we used IL-1 converting enzyme knockout mice, which exhibit deficient IL-1 bioactivity. The level of serum S-SMase activity in LPS-injected IL-1 converting enzyme knockout mice was ≈35% less than that in identically treated wild-type mice (
P
< 0.01). In LPS-injected IL-1-receptor antagonist knockout mice, which have an enhanced response to IL-1, serum S-SMase activity was increased 1.8-fold compared with LPS-injected wild-type mice (
P
< 0.01). Finally, when wild-type mice were injected directly with IL-1β, tumor necrosis factor α, or both, serum S-SMase activity increased 1.6-, 2.3-, and 2.9-fold, respectively (
P
< 0.01). These data show regulation of S-SMase activity
in vivo
and they raise the possibility that local stimulation of S-SMase may contribute to the effects of inflammatory cytokines in atherosclerosis.
A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver
Authors: Yamashita Hiromi , Takenoshita Makoto , Sakurai Masaharu , Bruick Richard K. , Henzel William J. , Shillinglaw Wendy , Arnot David , Uyeda Kosaku
Published: July 2002

Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity
in vitro
precisely correlates with promoter activity
in vivo
. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated
in vitro
by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.
Toll-related receptors and the control of antimicrobial peptide expression inDrosophila
Authors: Tauszig Servane , Jouanguy Emmanuelle , Hoffmann Jules A. , Imler Jean-Luc
Published: July 2002

Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides.Drosophilahas appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additionalToll-related genes (Toll-3toToll-8) inDrosophilain addition to18-wheeler. Two of these genes,Toll-3andToll-4, are expressed at a low level.Toll-6,-7, and-8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, likeTolland18w, they perform developmental functions. Finally,Toll-5is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.
Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy
Authors: Hlavacek William S. , Stilianakis Nikolaos I. , Notermans Daan W. , Danner Sven A. , Perelson Alan S.
Published: July 2002

Drug treatment of HIV type 1 (HIV-1) infection leads to a rapid initial decay of plasma virus followed by a slower second phase of decay. To investigate the role of HIV-1 retained on follicular dendritic cells (FDCs) in this process, we have developed and analyzed a mathematical model for HIV-1 dynamics in lymphoid tissue (LT) that includes FDCs. Analysis of clinical data using this model indicates that decay of HIV-1 during therapy may be influenced by release of FDC-associated virus. The biphasic character of viral decay can be explained by reversible multivalent binding of HIV-1 to receptors on FDCs, indicating that the second phase of decay is not necessarily caused by long-lived or latently infected cells. Furthermore, viral clearance and death of short-lived productively infected cells may be faster than previously estimated. The model, with reasonable parameter values, is consistent with kinetic measurements of viral RNA in plasma, viral RNA on FDCs, productively infected cells in LT, and CD4+T cells in LT during therapy.
Borrelia burgdorferi
periplasmic flagella have both skeletal and motility functions
Authors: Motaleb Mohammed Abdul , Corum Linda , Bono James L. , Elias Abdallah F. , Rosa Patricia , Samuels D. Scott , Charon Nyles W.
Published: July 2002

Bacterial shape usually is dictated by the peptidoglycan layer of
the cell wall. In this paper, we show that the morphology of the Lyme
disease spirochete
Borrelia burgdorferi
is the result of
a complex interaction between the cell cylinder and the internal
periplasmic flagella.
B. burgdorferi
has a bundle of
7–11 helically shaped periplasmic flagella attached at each end of the
cell cylinder and has a flat-wave cell morphology. Backward moving,
propagating waves enable these bacteria to swim in both low viscosity
media and highly viscous gel-like media. Using targeted mutagenesis, we
inactivated the gene encoding the major periplasmic flagellar filament
protein FlaB. The resulting
flaB
mutants not only were
nonmotile, but were rod-shaped. Western blot analysis indicated that
FlaB was no longer synthesized, and electron microscopy revealed that
the mutants were completely deficient in periplasmic flagella.
Wild-type cells poisoned with the protonophore carbonyl
cyanide-
m
-chlorophenylhydrazone retained their flat-wave
morphology, indicating that the periplasmic flagella do not need to be
energized for the cell to maintain this shape. Our results indicate
that the periplasmic flagella of
B. burgdorferi
have a
skeletal function. These organelles dynamically interact with the
rod-shaped cell cylinder to enable the cell to swim, and to confer in
part its flat-wave morphology.
Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumorin vivo
Authors: Cerwenka Adelheid , Baron Jody L. , Lanier Lewis L.
Published: July 2002

In 1986, Kärre and colleagues reported that natural killer (NK) cells rejected an MHC class I-deficient tumor cell line (RMA-S) but they did not reject the same cell line if it expressed MHC class I (RMA). Based on this observation, they proposed the concept that NK cells provide immune surveillance for “missing self,” e.g., they eliminate cells that have lost class I MHC antigens. This seminal observation predicted the existence of inhibitory NK cell receptors for MHC class I. Here, we present evidence that NK cells are able to reject tumors expressing MHC class I if the tumor expresses a ligand for NKG2D. Mock-transfected RMA cells resulted in tumor formation. In contrast, when RMA cells were transfected with the retinoic acid early inducible gene-1 γ or δ (RAE-1), ligands for the activating receptor NKG2D, the tumors were rejected. The tumor rejection was mediated by NK cells, and not by CD1-restricted NK1.1+T cells. No T cell-mediated immunological memory against the parental tumor was generated in the animals that had rejected the RAE-1 transfected tumors, which succumbed to rechallenge with the parental RMA tumor. Therefore, NK cells are able to reject a tumor expressing RAE-1 molecules, despite expression of self MHC class I on the tumor, demonstrating the potential for NK cells to participate in immunity against class I-bearing malignancies.