bluuebunny/crossref_metadata_2025 huggingface dataset:
Drift wave vortices and anomalous transport
Authors: Horton W.
Published: July 2002

Theory and computer simulations are used to describe the inelastic vortex–vortex and vortex–wave interactions that lead to the quasicoherent transport of plasma across a constant magnetic field in 2-D systems. Monopole and dipole drift wave vortices with radii r0 large compared with the ion inertial scale length ρs are shown to produce transport at the rate un ∫ dσ(b)≤nvvder0, where nv is the vortex line density and dσ(b) is the inelastic collision cross section for the impact parameter b. The transport during collisions and mergings is evaluated from the evolution of a passively convected scalar concentration of test particles.
A fully kinetic, self-consistent particle simulation model of the collisionless plasma–sheath region
Authors: Procassini R. J. , Birdsall C. K. , Morse E. C.
Published: July 2002

A fully kinetic particle-in-cell (PIC) model is used to self-consistently determine the steady-state potential profile in a collisionless plasma that contacts a floating, absorbing boundary. To balance the flow of particles to the wall, a distributed source region is used to inject particles into the one-dimensional system. The effect of the particle source distribution function on the source region and collector sheath potential drops, and particle velocity distributions is investigated. The ion source functions proposed by Emmert et al. [Phys. Fluids 23, 803 (1980)] and Bissell and Johnson [Phys. Fluids 30, 779 (1987)] (and various combinations of these) are used for the injection of both ions and electrons. The values of the potential drops obtained from the PIC simulations are compared to those from the theories of Emmert et al., Bissell and Johnson, and Scheuer and Emmert [Phys. Fluids 31, 3645 (1988)], all of which assume that the electron density is related to the plasma potential via the Boltzmann relation. The values of the source region and total potential drop are found to depend on the choice of the electron source function, as well as the ion source function. The question of an infinite electric field at the plasma–sheath interface, which arises in the analyses of Bissell and Johnson and Scheuer and Emmert, is also addressed.
Weakly nonlinear hydrodynamic instabilities in inertial fusion
Authors: Haan S. W.
Published: July 2002

For many cases of interest to inertial fusion, growth of Rayleigh–Taylor and other hydrodynamic instabilities is such that the perturbations remain linear or weakly nonlinear. The transition to nonlinearity is studied via a second-order solution for multimode classical Rayleigh–Taylor growth. The second-order solution shows how classical Rayleigh–Taylor systems forget initial amplitude information in the weakly nonlinear phase. Stabilized growth relevant to inertial fusion is qualitatively different, and initial amplitudes are not dominated by nonlinear effects. In all systems with a full spectrum of modes, nonlinear effects begin when mode amplitudes reach about 1/Lk2, for modes of wave number k and system size L.
Relativistic backward-wave oscillators: Theory and experiment
Authors: Levush B. , Antonsen T. , Bromborsky A. , Lou W. R. , Carmel Y.
Published: July 2002

Microwave sources based on backward-wave oscillators driven by relativistic electron beams are capable of producing high-power coherent radiation in cm and mm wavelength regime. Although there have been a number of experiments reported over the last decade on this topic, there are only a few publications providing a theoretical description of these devices. Thus, there is a need for theoretical models which can be compared in detail with the experimental data. This work is devoted to fill this need and applied to the University of Maryland backward-wave oscillator experiment. It is shown that the theoretical predictions for the threshold current to start the oscillations, the frequency characteristics, and the efficiency of the device compared favorably with the experimental data.
Karhunen–Loéve expansion of Burgers’ model of turbulence
Authors: Chambers D. H. , Adrian R. J. , Moin P. , Stewart D. S. , Sung H. J.
Published: July 2002

Characteristics of the Karhunen–Loéve expansion of a strongly inhomogeneous random process possessing small viscous length scales and a large outer scale have been investigated in relation to the application of the expansion to turbulent flow fields. Monte Carlo simulations of a randomly forced Burgers’ equation with zero velocity boundary conditions generate the random process numerically and the Karhunen–Loéve (KL) eigenfunctions and the eigenvalue spectra are computed for different Reynolds numbers. The eigenfunctions possess thin viscous boundary layers at the walls and are independent of Reynolds number in the core, where the random process is quasihomogeneous. The eigenfunctions and eigenvalues of the outer, large scale motions obey a principle of Reynolds number similarity. Eigenvalue spectra contain much of the energy in the first few modes, but they are as broad as ordinary trigonometric power spectra. The rate at which the expansion converges to within 90% of the total energy decreases with increasing Reynolds numbers and the expansion of the mean plus the fluctuation converges more rapidly than the expansion of the fluctuation alone.
Vortex deformation in elliptic-core jets from the perspective of linear instability analysis
Authors: Koshigoe Shozo , Tubis Arnold , Ho Chih-Ming
Published: July 2002

An attempt is made to identify the underlying mechanisms for the deformation of coherent structures that occurs in the initial state of axis switching of elliptic-core jets. The generalized shooting method is applied to jets with elliptic-core regions of constant flow. The analysis shows that there are three conditions on groups of eigenmodes of elliptic-core jets which are necessary for the deformation. They are (1) proper localizations without excessive overlapping; (2) sufficiently large phase-speed differences; and (3) comparable spatial amplification rates. The qualitative behaviors of elliptic-core jets in relation to these three conditions are studied with respect to independent and joint variations of core eccentricity, azimuthal distribution of momentum thickness, and compressibility.
The velocity field created by a shallow bump in a boundary layer
Authors: Gaster M. , Grosch C. E. , Jackson T. L.
Published: July 2002

The results of measurements of the disturbance velocity field generated in a boundary layer by a shallow three-dimensional bump oscillating at a very low frequency on the surface of a flat plate are reported. The disturbance was entirely confined to the boundary layer. Profiles of the mean velocity, the disturbance velocity at the fundamental frequency, and at the first harmonic are presented. These profiles were measured both upstream and downstream of the oscillating bump. About 100 boundary layer thicknesses downstream of the bump the intensity had a maximum near η=2, with a magnitude of about 0.2%. Measurements of the disturbance velocity were also made at various spanwise and downstream locations at a fixed distance from the boundary of one displacement thickness. The spanwise profiles of the disturbance field changed dramatically from the near-field region of the bump to the far downstream region. Finally, the spanwise spectrum of the disturbances at three locations downstream of the bump are presented. The spanwise spectrum of the disturbance showed a primary peak consistent with the motion and geometry of the driver. This peak decreased slowly with downstream distance. In addition, a small secondary peak in the spanwise spectrum was apparent near the bump. This peak increased rapidly with downstream distance.
Exit flows from highly porous media
Authors: Hall M. J. , Hiatt J. P.
Published: July 2002

This paper presents laser velocimetry measurements of the streamwise component of mean velocities and turbulence intensities measured downstream from the exit plane of porous ceramic foams through which air is flowed. The recent development and commercial availability of porous ceramic foams has lead to their application in many fields. Their uses have extended to combustion, high-temperature fluid filtering, biotechnology, and as support matrix for catalysts. These applications have created an interest in their pore scale fluid mechanics, both within the porous matrix and along surfaces open to flow. One emerging application is porous ceramic burners which combust liquid or gaseous fuels within the pore matrix or along the surface of the ceramic. The ceramic foams have pore sizes ranging from 4 to 12 pores per cm (ppcm) and porosities of 85%. Mean velocities between 0.3 and 1.5 m/s were examined. Radial distributions of mean velocities show a jet-like structure through the pores, with local mean velocities reaching maximum values over two times the area mean velocity. Negative mean velocities were often observed between pores, suggesting that recirculation zones are present above the web-like struts surrounding the pores. Levels of turbulence intensities normalized by the area mean velocity ranged from 0.05 to 0.6 for the various flow rates and pore sizes. Turbulence intensities were found to increase with increasing pore size for a given flow rate.
A method for calculating hydrodynamic interactions between two bodies in low Mach number free-molecular flows with application to the resistivity functions for two aligned cylinders
Authors: Gopinath Arvind , Koch Donald L.
Published: July 2002

Aerosol particles in flames or in the upper reaches of the atmosphere have, in many cases, dimensions comparable to or smaller than the local mean free path, λ. In order to predict the collision and coagulation rates between particles smaller than λ, accurate expressions for the torques and forces due to hydrodynamic interactions between the particles in the free-molecular regime are needed. In this article, we propose a general method to study the hydrodynamic interactions between two convex bodies moving in an extremely rarefied gas. The particle sizes and inter-particle separation are assumed to be smaller than the mean free path of the gas. Under conditions of small Mach number, the governing equations are quasi-steady and linear. The problem is reduced to solving two coupled integral equations for the molecular number densities at the particle surfaces. The induced forces and torques are then calculated by simple quadrature. Using this method, we study the hydrodynamic interactions between two infinitely long, right circular cylinders, of equal radii, a, separated by a center to center distance, aχ. In many cases, the qualitative nature of the forces and torques in the free-molecular regime are quite different from that in the corresponding continuum flow low Reynolds number problems.
Nonlinear dynamical behavior of thermionic low pressure discharges. II. Experimental
Authors: Klinger T. , Greiner F. , Rohde A. , Piel A.
Published: July 2002

Strongly nonlinear relaxation oscillations of discharge current and plasma potential are investigated in a magnetized thermionic plasma discharge. The quasi-one-dimensional electron motion allows a direct comparison with one-dimensional models and computer simulations. Two different stable discharge modes can be established, the low-current space charge limited and the high-current temperature limited mode. Time resolved probe measurements of the plasma potential distribution demonstrate that the current oscillations result from a strongly nonlinear instability of the potential structure in the weak current discharge mode. This confirms the model based on particle-in-cell simulations [F. Greiner et al., Phys. Plasmas 2, 1810 (1995)]. The oscillation process consists of three distinct phases. The sequence of events and the observed parameter dependencies of the oscillation frequency is in accordance with the model. The periodically driven system shows the characteristic behavior of nonlinear oscillators: quasiperiodicity, mode-locking, and period doubling sequences towards chaos. It is possible to link the complex dynamical behavior to the details of the trigger mechanism that are revealed by the simulation.
Capacitive, inductive and helicon-wave modes of operation of a helicon plasma source
Authors: Ellingboe A. R. , Boswell R. W.
Published: July 2002

Vector-rf-B-field measurements in the near-field of a helicon plasma source taken throughout the volume of the source are reported. Three distinct modes of operation of the helicon plasma source, capacitive, inductive, and helicon-wave, are identified by the structure of the plasma-wave-fields. Results are reported for a double-half-turn antenna, which is believed to be the first reporting for such an antenna structure in application to helicon-wave plasma sources. Comparison is made to a double-saddle-coil antenna which also demonstrates the distinct inductive and helicon-wave modes.
Dependence of tunneling current on structural variations of superlattice devices
Authors: Jogai B. , Wang K. L.
Published: July 2002

The tunneling current of a three-terminal, double-barrier superlattice device has been calculated by solving the Schrödinger equation. The results indicate that the negative resistance resulting from resonant tunneling can be adjusted by varying the bias voltages. Use of multiple barriers has been explored. In particular, we have examined the effect on the tunneling current of asymmetric wells and barrier heights. Deviations from perfect symmetry are seen to produce radical changes in the results. The detailed features of the I-V curve could be used to probe the superlattice structure.
Focused ion beam induced deposition of gold
Authors: Shedd G. M. , Lezec H. , Dubner A. D. , Melngailis J.
Published: July 2002

A finely focused ion beam is scanned over a surface on which a local gas ambient of dimethyl gold hexafluoro acetylacetonate is created by a directed miniature nozzle. The incident ions induce the selective deposition of gold along the path traced by the beam. The 15-keV Ga+ ion beam current is 100 pA and the beam diameter is 0.5 μm. Gold lines of 0.5 μm width and Gaussian profile are written. The film growth rate corresponds to five atoms deposited per incident ion. The focused ion beam deposited films contained 15% Ga, but less than 5% of other impurities, such as O or C. Deposition was also observed with broad ion beams of 750 eV Ar+ and 50 keV Si+. The resistivity of the films varied from 2×10−5 to 1.3×10−3 Ω cm.
Large volume, high density rf inductively coupled plasma
Authors: Boswell R. W. , Porteous R. K.
Published: July 2002

Magnetized argon plasma columns with peak densities of greater than 1018 m−3, lengths of 2 m, and full width half-maximum diameters of 0.3 m have been created at pressures of 40 mPa (3×10−4 Torr) with input powers of 1.5 kW of 7 MHz rf.
Fluid loading of a Lamb-wave sensor
Authors: White R. M. , Wenzel S. W.
Published: July 2002

We describe the fluid loading of Lamb waves propagating in a 3 mm×9 mm composite membrane consisting of low-stress silicon nitride deposited by low-pressure chemical vapor deposition (2.0 μm thick) supporting an aluminum ground plane (0.3 μm), a piezoelectric zinc oxide layer (0.7 μm), and a pair of 100-μm-period interdigital Al transducers (0.5 μm). When this device is operated in air, the phase velocity of the lowest antisymmetric mode is 474 m/s; it changes to 304 and 322 m/s, respectively, when the membrane is loaded on one side with de-ionized water and with methanol. The large fluid-loading effect, in excellent agreement with theory, and the stability of an oscillator made with this membrane (stability better than 1 part in 106) suggest the utility of the device as a sensitive densitometer and pressure sensor.
Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus
Authors: Chin Keh-Chuang , Cresswell Peter
Published: July 2002

Little is known about the mechanism by which IFNs inhibit human cytomegalovirus (HCMV) replication. Indeed, infection of fibroblasts with HCMV initiates the expression of a subset of type I IFN-inducible genes whose role in the infectious process is unclear. We describe here the identification of a cytoplasmic antiviral protein that is induced by IFNs, by HCMV infection, and by the HCMV envelope protein, glycoprotein B (gB). Stable expression of the protein in fibroblasts inhibits productive HCMV infection, down-regulating several HCMV structural proteins (gB, pp28, and pp65) known to be indispensable for viral assembly and maturation. We have named the protein viperin (forvirusinhibitoryprotein,endoplasmicreticulum-associated,interferon-inducible). HCMV infection causes the redistribution of the induced viperin from its normal endoplasmic reticulum association, first to the Golgi apparatus and then to cytoplasmic vacuoles containing gB and pp28. Expression before HCMV infection reduces viperin redistribution from the endoplasmic reticulum to the Golgi apparatus and prevents vacuolar localization, perhaps reflecting the mechanism used by HCMV to evade the antiviral function.
Integration of Shaker-type K
+
channel, KAT1, into the endoplasmic reticulum membrane: Synergistic insertion of voltage-sensing segments, S3–S4, and independent insertion of pore-forming segments, S5–P–S6
Authors: Sato Yoko , Sakaguchi Masao , Goshima Shinobu , Nakamura Tatsunosuke , Uozumi Nobuyuki
Published: July 2002

KAT1 is a member of the Shaker family of voltage-dependent
K
+
channels, which has six transmembrane segments (called
S1–S6), including an amphipathic S4 with several positively charged
residues and a hydrophobic pore-forming region (called P) between S5
and S6. In this study, we systematically evaluated the function
of individual and combined transmembrane segments of KAT1 to direct the
final topology in the endoplasmic reticulum membrane by
in
vitro
translation and translocation experiments. The assay with
single-transmembrane constructs showed that S1 possesses the type II
signal-anchor function, whereas S2 has the stop-transfer function. The
properties fit well with the results derived from combined insertion of
S1 and S2. S3 and S4 failed to integrate into the membrane by
themselves. The inserted glycosylation sequence at the S3–S4 loop
neither prevented the translocation of S3 and S4 nor impaired the
function of voltage-dependent K
+
transport regardless of
the changed length of the S3–S4 loop. S3 and S4 are likely to be
posttranslationally integrated into the membrane only when somewhat
specific interaction occurs between them. S5 had the ability of
translocation reinitiation, and S6 had a strong preference for
N
exo
/C
cyt
orientation. The pore region
resided outside because of its lack of its transmembrane-spanning
property. According to their own topogenic function, combined
constructs of S5–P–S6 conferred the membrane-pore-membrane topology.
This finding supports the notion that a set of S5–P–S6 can be
independently integrated into the membrane. The results in this study
provide the fundamental topogenesis mechanism of transmembrane segments
involving voltage sensor and pore region in KAT1.
Potent antiarthritic properties of a glucocorticoid derivative, NCX-1015, in an experimental model of arthritis
Authors: Paul-Clark Mark J. , Mancini Lucia , Del Soldato Piero , Flower Roderick J. , Perretti Mauro
Published: July 2002

Here, we describe the improved antiarthritic properties of a nitric oxide-releasing derivative of prednisolone that includes a sparing of the effects on bone. Glucocorticoids are widely used in the treatment of chronic inflammatory pathologies, but their use is often accompanied by side effects, including osteoporosis. Recently, a new steroid able to release low levels of nitric oxide showed potent inhibition of leukocyte trafficking and chemokine generation in models of acute inflammation. The objective of this study was to assess the anti-inflammatory activity of this nitric-oxide releasing glucocorticoid, nitro-prednisolone (NCX-1015), in parallel with the parent compound prednisolone and a control molecule lacking an NO group, (NCX-1016), in a model of rat collagen-induced arthritis. Dosing of rats with NCX-1015 (0.4–4 μmol/kg, i.p.) greatly reduced all parameters of inflammation. A significant but inferior anti-inflammatory effect also was obtained with prednisolone. Collagen-induced arthritic rats had elevated pyridinoline values (>60% over naïve rats), indicating bone and cartilage erosion; this increase was prevented by NCX-1015 but not by prednisolone or NCX-1016 treatment.In vitro, prednisolone (1 nM), but not NCX-1015, elevated bone resorbing activity of rat primary osteoclasts. In conclusion, NCX-1015 is a steroid derivative with a potential for the treatment of chronic inflammatory pathologies and that has milder side effects anticipated on the bone compartment.
Stochastic and mesoscopic models for tropical convection
Authors: Majda Andrew J. , Khouider Boualem
Published: July 2002

A new way to parametrize certain aspects of tropical convection through stochastic and mesoscopic models is developed here. The technical idea is to adapt tools from statistical physics and materials science to model important unresolved features of tropical convection. This new strategy consists of modeling the unresolved effects of convective inhibition in a coarse mesh mesoscopic parametrization through a “heat bath” model involving a stochastic spin flip model with very natural interaction rules for convective inhibition combined with a suitable external potential defined by the coarse mesh values. In turn, the values of the order parameter from this heat bath alter the vertical mass flux in regions of deep convection. Both stochastic and systematic deterministic mesoscopic parametrizations are developed here. The deterministic mesoscopic models derived in this fashion exhibit new phenomena such as multiple radiative equilibria in suitable parameter regimes. The simplest first numerical experiments reported here with the mesoscopic deterministic parametrization qualitatively reproduce several key features of the observational record regarding convectively coupled tropical waves. The systematic stochastic modeling strategy proposed here could also be very useful for capturing other features of tropical convection such as those involving cloud radiation feedbacks.
Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
Authors: Holtzman David M. , Bales Kelly R. , Tenkova Tanya , Fagan Anne M. , Parsadanian Maia , Sartorius Leah J. , Mackey Brian , Olney John , McKeel Daniel , Wozniak David , Paul Steven M.
Published: July 2002

Apolipoprotein E (apoE) alleles determine the age-adjusted relative
risk (ɛ4 > ɛ3) for Alzheimer's disease (AD). ApoE may affect
AD pathogenesis by promoting deposition of the amyloid-β (Aβ)
peptide and its conversion to a fibrillar form. To determine the effect
of apoE on Aβ deposition and AD pathology, we compared
APP
V717F
transgenic (TG) mice expressing mouse, human, or
no apoE (apoE
−/−
). A severe, plaque-associated neuritic
dystrophy developed in APP
V717F
TG mice expressing mouse or
human apoE. Though significant levels of Aβ deposition also occurred
in APP
V717F
TG, apoE
−/−
mice, neuritic
degeneration was virtually absent. Expression of apoE3 and apoE4 in
APP
V717F
TG, apoE
−/−
mice resulted in
fibrillar Aβ deposits and neuritic plaques by 15 months of age and
substantially (>10-fold) more fibrillar deposits were observed in
apoE4-expressing APP
V717F
TG mice. Our data demonstrate a
critical and isoform-specific role for apoE in neuritic plaque
formation, a pathological hallmark of AD.
Top-down morphogenesis of colorectal tumors
Authors: Shih Ie-Ming , Wang Tian-Li , Traverso Giovanni , Romans Kathy , Hamilton Stanley R. , Ben-Sasson Shmuel , Kinzler Kenneth W. , Vogelstein Bert
Published: July 2002

One of the fundamental tenets of oncology is that tumors arise from stem cells. In the colon, stem cells are thought to reside at the base of crypts. In the early stages of tumorigenesis, however, dysplastic cells are routinely found at the luminal surface of the crypts whereas the cells at the bases of these same crypts appear morphologically normal. To understand this discrepancy, we evaluated the molecular characteristics of cells isolated from the bases and orifices of the same crypts in small colorectal adenomas. We found that the dysplastic cells at the tops of the crypts often exhibited genetic alterations of adenomatous polyposis coli (APC) and neoplasia-associated patterns of gene expression. In contrast, cells located at the base of these same crypts did not contain such alterations and were not clonally related to the contiguous transformed cells above them. These results imply that development of adenomatous polyps proceeds through a top-down mechanism. Genetically altered cells in the superficial portions of the mucosae spread laterally and downward to form new crypts that first connect to preexisting normal crypts and eventually replace them.
Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease
Authors: Vila Miquel , Jackson-Lewis Vernice , Vukosavic Slobodanka , Djaldetti Ruth , Liberatore Gabriel , Offen Daniel , Korsmeyer Stanley J. , Przedborski Serge
Published: July 2002

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages
dopaminergic neurons in the substantia nigra pars compacta (SNpc) as
seen in Parkinson's disease. Here, we show that the pro-apoptotic
protein Bax is highly expressed in the SNpc and that its ablation
attenuates SNpc developmental neuronal apoptosis. In adult
mice, there is an up-regulation of Bax in the SNpc after MPTP
administration and a decrease in Bcl-2. These changes parallel
MPTP-induced dopaminergic neurodegeneration. We also show that mutant
mice lacking Bax are significantly more resistant to MPTP than their
wild-type littermates. This study demonstrates that Bax plays a
critical role in the MPTP neurotoxic process and suggests that
targeting Bax may provide protective benefit in the treatment of
Parkinson's disease.
A new evolutionary scenario for the
Mycobacterium tuberculosis
complex
Authors: Brosch R. , Gordon S. V. , Marmiesse M. , Brodin P. , Buchrieser C. , Eiglmeier K. , Garnier T. , Gutierrez C. , Hewinson G. , Kremer K. , Parsons L. M. , Pym A. S. , Samper S. , van Soolingen D. , Cole S. T.
Published: July 2002

The distribution of 20 variable regions resulting from insertion-deletion events in the genomes of the tubercle bacilli has been evaluated in a total of 100 strains of
Mycobacterium tuberculosis
,
Mycobacterium africanum
,
Mycobacterium canettii
,
Mycobacterium microti
, and
Mycobacterium bovis
. This approach showed that the majority of these polymorphisms did not occur independently in the different strains of the
M. tuberculosis
complex but, rather, resulted from ancient, irreversible genetic events in common progenitor strains. Based on the presence or absence of an
M. tuberculosis
specific deletion (TbD1),
M. tuberculosi
s strains can be divided into ancestral and “modern” strains, the latter comprising representatives of major epidemics like the Beijing, Haarlem, and African
M. tuberculosis
clusters. Furthermore, successive loss of DNA, reflected by region of difference 9 and other subsequent deletions, was identified for an evolutionary lineage represented by
M. africanum
,
M. microti
, and
M. bovis
that diverged from the progenitor of the present
M. tuberculosis
strains before TbD1 occurred. These findings contradict the often-presented hypothesis that
M. tuberculosis,
the etiological agent of human tuberculosis evolved from
M. bovis
, the agent of bovine disease.
M. canettii
and ancestral
M. tuberculosis
strains lack none of these deleted regions, and, therefore, seem to be direct descendants of tubercle bacilli that existed before the
M. africanum→M. bovis
lineage separated from the
M. tuberculosis
lineage. This observation suggests that the common ancestor of the tubercle bacilli resembled
M. tuberculosis
or
M. canettii
and could well have been a human pathogen already.
How many named species are valid?
Authors: Alroy John
Published: July 2002

Estimates of biodiversity in both living and fossil groups depend on raw counts of currently recognized named species, but many of these names eventually will prove to be synonyms or otherwise invalid. This difficult bias can be resolved with a simple “flux ratio” equation that compares historical rates of invalidation and revalidation. Flux ratio analysis of a taxonomic data set of unrivalled completeness for 4,861 North American fossil mammal species shows that 24–31% of currently accepted names eventually will prove invalid, so diversity estimates are inflated by 32–44%. The estimate is conservative compared with one obtained by using an older, more basic method. Although the degree of inflation varies through both historical and evolutionary time, it has a minor impact on previously published background origination and extinction rates. Several lines of evidence suggest that the same bias probably affects more poorly studied, hyperdiverse living groups such as fungi and insects. If so, then current estimates of total global diversity could be revised downwards to as low as 3.5–10.5 million species.
Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores
Authors: Sharma Geeta , Vijayaraghavan Sukumar
Published: July 2002

In this report we provide evidence that neuronal nicotinic
acetylcholine receptors (nAChRs) are present on hippocampal astrocytes
and their activation produces rapid currents and calcium transients.
Our data indicate that these responses obtained from astrocytes are
primarily mediated by an AChR subtype that is functionally blocked by
α-bungarotoxin (αBgt) and contains the α7 subunit (αBgt-AChRs).
Furthermore, their action is unusual in that they effectively increase
intracellular free calcium concentrations by activating calcium-induced
calcium release from intracellular stores, triggered by influx through
the receptor channels. These results reveal a mechanism by which
αBgt-AChRs on astrocytes can efficiently modulate calcium signaling
in the central nervous system in a manner distinct from that observed
with these receptors on neurons.
Rab geranylgeranyl transferase α mutation in the
gunmetal
mouse reduces Rab prenylation and platelet synthesis
Authors: Detter John C. , Zhang Qing , Mules Emilie H. , Novak Edward K. , Mishra Vishnu S. , Li Wei , McMurtrie Elzbieta B. , Tchernev Velizar T. , Wallace Margaret R. , Seabra Miguel C. , Swank Richard T. , Kingsmore Stephen F.
Published: July 2002

Few molecular events important to platelet biogenesis have been identified. Mice homozygous for the spontaneous, recessive mutation
gunmetal
(
gm
) have prolonged bleeding, thrombocytopenia, and reduced platelet α- and δ-granule contents. Here we show by positional cloning that
gm
results from a G→A substitution mutation in a splice acceptor site within the α-subunit of Rab geranylgeranyl transferase (
Rabggta
), an enzyme that attaches geranylgeranyl groups to Rab proteins. Most Rabggta mRNAs from
gm
tissues skipped exon 1 and lacked a start codon. Rabggta protein and Rab geranylgeranyl transferase (GGTase) activity were reduced 4-fold in
gm
platelets. Geranylgeranylation and membrane association of Rab27, a Rab GGTase substrate, were significantly decreased in
gm
platelets. These findings indicate that geranylgeranylation of Rab GTPases is critical for hemostasis. Rab GGTase inhibition may represent a new treatment for thrombocytosis and clotting disorders.
Factors regulating template switch
in vitro
by viral RNA-dependent RNA polymerases: Implications for RNA–RNA recombination
Authors: Kim M.-J. , Kao C.
Published: July 2002

Copy-choice RNA recombination occurs during viral RNA synthesis
when the viral transcription complex switches templates. We demonstrate
that RNA-dependent RNA polymerase from bovine viral diarrhea virus and
the replicases from three plant-infecting RNA viruses can produce
easily detectable recombination products
in vitr
o by
switching templates during elongative RNA synthesis. Template sequence
and/or structure, and NTP availability affected the frequency of
template switch by the transcription complex. Our results provide
biochemical support for copy-choice recombination and establish assays
for mechanistic analyses of intermolecular RNA recombination
in
vitro
.
Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40
in vitro
and
in vivo
Authors: Fassbender K. , Simons M. , Bergmann C. , Stroick M. , Lütjohann D. , Keller P. , Runz H. , Kühl S. , Bertsch T. , von Bergmann K. , Hennerici M. , Beyreuther K. , Hartmann T.
Published: July 2002

Recent epidemiological studies show a strong reduction in the
incidence of Alzheimer's disease in patients treated with
cholesterol-lowering statins. Moreover, elevated Aβ42 levels and the
ɛ4 allele of the lipid-carrier apolipoprotein E are regarded as risk
factors for sporadic and familial Alzheimer's disease. Here we
demonstrate that the widely used cholesterol-lowering drugs simvastatin
and lovastatin reduce intracellular and extracellular levels of Aβ42
and Aβ40 peptides in primary cultures of hippocampal neurons and
mixed cortical neurons. Likewise, guinea pigs treated with high doses
of simvastatin showed a strong and reversible reduction of cerebral
Aβ42 and Aβ40 levels in the cerebrospinal fluid and brain
homogenate. These results suggest that lipids are playing an important
role in the development of Alzheimer's disease. Lowered levels of
Aβ42 may provide the mechanism for the observed reduced incidence of
dementia in statin-treated patients and may open up avenues for
therapeutic interventions.
Galactolipid deficiency and abnormal chloroplast development in the
Arabidopsis MGD synthase 1
mutant
Authors: Jarvis Paul , Dörmann Peter , Peto Charles A. , Lutes Jason , Benning Christoph , Chory Joanne
Published: July 2002

The lipid monogalactosyl diacylglycerol (MGD) is a major structural component of photosynthetic membranes in chloroplasts. Its formation is catalyzed by the enzyme MGD synthase. In many plants, MGD derives from two different biosynthetic pathways: the prokaryotic pathway, which operates entirely within the plastid, and the eukaryotic pathway, which involves steps in the endoplasmic reticulum. Here, we describe the identification and characterization of an
Arabidopsis
mutant with a defective MGD synthase gene (
MGD1
). The mutant was identified in a screen of T-DNA lines for individuals with defects in chloroplast biogenesis. It has a yellow-green phenotype that correlates with a ≈50% deficiency in total chlorophyll per plant. A single T-DNA insertion is located adjacent to the transcription initiation site of the
MGD1
gene, and the abundance of
MGD1
mRNA is reduced by 75% compared with wild type. Correlation between steady-state
MGD1
transcript levels and MGD synthase activity (also reduced by 75% in
mgd1
) suggests that MGD1 is the most important MGD synthase in green tissues. The amount of MGD in mutant leaves is reduced by 42% compared with wild type. MGD from the mutant contains 23% less 16:3 fatty acid and 10% more 18:3 fatty acid. Because 16:3 is a characteristic feature of MGD from the prokaryotic pathway, it is possible that MGD1 operates with some preference in the prokaryotic pathway. Finally, the MGD-deficiency of
mgd1
is correlated with striking defects in chloroplast ultrastructure, strongly suggesting a unique role for MGD in the structural organization of plastidic membranes.
Bruchins: Insect-derived plant regulators that stimulate neoplasm formation
Authors: Doss Robert P. , Oliver James E. , Proebsting William M. , Potter Sandra W. , Kuy SreyReath , Clement Stephen L. , Williamson R. Thomas , Carney John R. , DeVilbiss E. David
Published: July 2002

Pea weevil (Bruchus pisorumL.) oviposition on pods of specific genetic lines of pea (Pisum sativumL.) stimulates cell division at the sites of egg attachment. As a result, tumor-like growths of undifferentiated cells (neoplasms) develop beneath the egg. These neoplasms impede larval entry into the pod. This unique form of induced resistance is conditioned by theNpallele and mediated by a recently discovered class of natural products that we have identified from both cowpea weevil (Callosobruchus maculatusF.) and pea weevil. These compounds, which we refer to as “bruchins,” are long-chain α,ω-diols, esterified at one or both oxygens with 3-hydroxypropanoic acid. Bruchins are potent plant regulators, with application of as little as 1 fmol (0.5 pg) causing neoplastic growth on pods of all of the pea lines tested. The bruchins are, to our knowledge, the first natural products discovered with the ability to induce neoplasm formation when applied to intact plants.
Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress
Authors: Brunson Kristen L. , Eghbal-Ahmadi Mariam , Bender Roland , Chen Yuncai , Baram Tallie Z.
Published: July 2002

Stress early in postnatal life may result in long-term memory deficits and selective loss of hippocampal neurons. The mechanisms involved are poorly understood, but they may involve molecules and processes in the immature limbic system that are activated by stressful challenges. We report that administration of corticotropin-releasing hormone (CRH), the key limbic stress modulator, to the brains of immature rats reproduced the consequences of early-life stress, reducing memory functions throughout life. These deficits were associated with progressive loss of hippocampal CA3 neurons and chronic up-regulation of hippocampal CRH expression. Importantly, they did not require the presence of stress levels of glucocorticoids. These findings indicate a critical role for CRH in the mechanisms underlying the long-term effects of early-life stress on hippocampal integrity and function.
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P
Authors: Schenck Annette , Bardoni Barbara , Moro Annamaria , Bagni Claudia , Mandel Jean-Louis
Published: July 2002

The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (
Cy
toplasmic
F
MRP
I
nteracting
P
roteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP–CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.
Conditional epidermal expression of TGFβ1 blocks neonatal lethality but causes a reversible hyperplasia and alopecia
Authors: Liu Xin , Alexander Valarie , Vijayachandra Kinnimulki , Bhogte Ervind , Diamond Ilysa , Glick Adam
Published: July 2002

To study the role of transforming growth factor type β1 (TGFβ1) in epidermal growth control and disease, we have generated a conditional expression system by using the bovine keratin 5 promoter to drive expression of the tetracycline-regulated transactivators tTA and rTA, and a constitutively active mutant of TGFβ1 linked to the tet
O
target sequence for the transactivator. This model allows for induction or suppression of exogenous TGFβ1 with oral doxycycline. Maximal expression of TGFβ1 during gestation caused embryonic lethality, whereas partial suppression allowed full-term development with neonatal lethality characterized by runting, epidermal hypoproliferation, and blocked hair follicle growth. With complete suppression, phenotypically normal double transgenic (DT) mice were born. Acute induction of TGFβ1 in the epidermis of adult mice inhibited basal and follicular keratinocyte proliferation and reentry of telogen hair follicles into anagen. However, chronic expression of TGFβ1 in adult DTs caused severe alopecia characterized by epidermal and follicular hyperproliferation, apoptosis, as well as dermal fibrosis and inflammation. Readministration of doxycycline to tTA DT mice caused hair regrowth within 14 days. The mRNA and protein for Smad7, an inhibitor of TGFβ signaling, were up-regulated in the epidermis and hair follicles of alopecic skin and rapidly induced in rTA mice in parallel with the TGFβ1 transgene, suggesting that the hyperproliferative phenotype may result in part from development of a sustained negative feedback loop. Thus, this conditional expression system provides an important model for understanding the role of TGFβ1 during development, in normal skin biology, and in disease.
Heart regeneration in adult MRL mice
Authors: Leferovich John M. , Bedelbaeva Khamilia , Samulewicz Stefan , Zhang Xiang-Ming , Zwas Donna , Lankford Edward B. , Heber-Katz Ellen
Published: July 2002

The reaction of cardiac tissue to acute injury involves interacting
cascades of cellular and molecular responses that encompass
inflammation, hormonal signaling, extracellular matrix remodeling, and
compensatory adaptation of myocytes. Myocardial regeneration is
observed in amphibians, whereas scar formation characterizes cardiac
ventricular wound healing in a variety of mammalian injury models. We
have previously shown that the MRL mouse strain has an extraordinary
capacity to heal surgical wounds, a complex trait that maps to at least
seven genetic loci. Here, we extend these studies to cardiac wounds and
demonstrate that a severe transmural, cryogenically induced infarction
of the right ventricle heals extensively within 60 days, with the
restoration of normal myocardium and function. Scarring is markedly
reduced in MRL mice compared with C57BL/6 mice, consistent with both
the reduced hydroxyproline levels seen after injury and an elevated
cardiomyocyte mitotic index of 10–20% for the MRL compared with
1–3% for the C57BL/6. The myocardial response to injury observed in
these mice resembles the regenerative process seen in amphibians.
ΔFosB: A sustained molecular switch for addiction
Authors: Nestler Eric J. , Barrot Michel , Self David W.
Published: July 2002

The longevity of some of the behavioral abnormalities that characterize drug addiction has suggested that regulation of neural gene expression may be involved in the process by which drugs of abuse cause a state of addiction. Increasing evidence suggests that the transcription factor ΔFosB represents one mechanism by which drugs of abuse produce relatively stable changes in the brain that contribute to the addiction phenotype. ΔFosB, a member of the Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum (brain regions important for addiction) after repeated administration of many kinds of drugs of abuse. Similar accumulation of ΔFosB occurs after compulsive running, which suggests that ΔFosB may accumulate in response to many types of compulsive behaviors. Importantly, ΔFosB persists in neurons for relatively long periods of time because of its extraordinary stability. Therefore, ΔFosB represents a molecular mechanism that could initiate and then sustain changes in gene expression that persist long after drug exposure ceases. Studies in inducible transgenic mice that overexpress either ΔFosB or a dominant negative inhibitor of the protein provide direct evidence that ΔFosB causes increased sensitivity to the behavioral effects of drugs of abuse and, possibly, increased drug seeking behavior. This work supports the view that ΔFosB functions as a type of sustained “molecular switch” that gradually converts acute drug responses into relatively stable adaptations that contribute to the long-term neural and behavioral plasticity that underlies addiction.
The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P
Authors: Lenz Oliver , ter Meulen Jan , Klenk Hans-Dieter , Seidah Nabil G. , Garten Wolfgang
Published: July 2002

The surface glycoprotein of the Lassa virus, a member of the
arenaviridae
family, is synthesized as a 76-kDa precursor (GP-C) that is posttranslationally cleaved into an N-terminal 44-kDa subunit and a C-terminal membrane-anchored 36-kDa subunit. Cleavage occurs at the C-terminal end of the unusual recognition motif R-R-L-L. We show here that GP-C is cleaved in the endoplasmic reticulum by the cellular subtilase SKI-1/S1P, an enzyme that has so far been observed to be involved in cholesterol metabolism. Furthermore, we present evidence that only cleaved glycoprotein is incorporated into virions and that this is necessary for the formation of infectious virus. To our knowledge, there have been no previous reports of this type of viral glycoprotein processing, one that may be an interesting target for antiviral therapy.
The North Atlantic Oscillation: Past, present, and future
Authors: Visbeck Martin H. , Hurrell James W. , Polvani Lorenzo , Cullen Heidi M.
Published: July 2002

The climate of the Atlantic sector exhibits considerable variability on a wide range of time scales. A substantial portion is associated with the North Atlantic Oscillation (NAO), a hemispheric meridional oscillation in atmospheric mass with centers of action near Iceland and over the subtropical Atlantic. NAO-related impacts on winter climate extend from Florida to Greenland and from northwestern Africa over Europe far into northern Asia. Over the last 3 decades, the phase of the NAO has been shifting from mostly negative to mostly positive index values. Much remains to be learned about the mechanisms that produce such low frequency changes in the North Atlantic climate, but it seems increasingly likely that human activities are playing a significant role.
Rapid activation of G
2
/M checkpoint after hypertonic stress in renal inner medullary epithelial (IME) cells is protective and requires p38 kinase
Authors: Dmitrieva Natalia I. , Bulavin Dmitry V. , Fornace Albert J. , Burg Maurice B.
Published: July 2002

Cells in the kidney medulla are subject to variable and
often extreme osmotic stress during concentration of the urine.
Previous studies showed that renal inner medullary epithelial (IME)
cells respond to hypertonicity by G
2
arrest. The purpose of
the present study was to investigate the mechanisms involved in
initiation and maintenance of G
2
arrest. Rapid initiation
of G
2
arrest after UV radiation is mediated by p38
kinase. Here we find that p38 kinase is responsible for rapid
initiation of the G
2
delay in IME cells after the
hypertonic stress created by adding NaCl. High NaCl, but not high urea,
rapidly initiates G
2
arrest. Inhibition of p38 kinase by
SB202190 (10 μM) blocks the rapid initiation of this checkpoint both
in an immortalized cell line (mIMCD3) and in second-passage IME cells
from mouse renal inner medulla. p38 inhibition does not affect exit
from G
2
arrest. The rapid initiation of G
2
arrest is followed by inhibition of cdc2 kinase, which is also
prevented by SB202190. To assess the possible protective role of
G
2
arrest, we measured DNA strand breaks as reflected by
immunostaining against phospho-histone H2AX, which becomes
phosphorylated on Ser-139 associated with DNA breaks. Abrogation of
rapid G
2
/M checkpoint activation by SB202190 increases
the histone H2AX phosphorylation in G
2
/M cells. We
propose that the rapid initiation of G
2
delay by p38 kinase
after hypertonicity protects the cells by decreasing the level of DNA
breaks caused by aberrant mitosis entry.