bluuebunny/crossref_metadata_2025 huggingface dataset:
On pressure and velocity boundary conditions for the lattice Boltzmann BGK model
Authors: Zou Qisu , He Xiaoyi
Published: July 2002

Pressure (density) and velocity boundary conditions are studied for 2-D and 3-D lattice Boltzmann BGK models (LBGK) and a new method to specify these conditions is proposed. These conditions are constructed in consistency with the wall boundary condition, based on the idea of bounceback of the non-equilibrium distribution. When these conditions are used together with the incompressible LBGK model [J. Stat. Phys. 81, 35 (1995)] the simulation results recover the analytical solution of the plane Poiseuille flow driven by a pressure (density) difference. The half-way wall bounceback boundary condition is also used with the pressure (density) inlet/outlet conditions proposed in this paper and in Phys. Fluids 8, 2527 (1996) to study 2-D Poiseuille flow and 3-D square duct flow. The numerical results are approximately second-order accurate. The magnitude of the error of the half-way wall bounceback boundary condition is comparable with that of other published boundary conditions and it has better stability behavior.
A dynamic model for subgrid-scale variance and dissipation rate of a conserved scalar
Authors: Pierce Charles D. , Moin Parviz
Published: July 2002

The dynamic procedure is applied to the problem of modeling the subgrid-scale variance and dissipation rate of a conserved scalar in large eddy simulations of turbulent reacting flows. A simple scaling relation for the subgrid-scale variance is proposed, and the coefficient of the scaling law is obtained using the dynamic procedure. The variance dissipation rate is modeled by assuming equilibrium with the local variance production rate, which is obtained using a dynamic model. Example model predictions are obtained using actual large eddy simulation data, and the subgrid variance predicted by the dynamic model is compared to results obtained using a scale similarity model. Generalization of the approach to multiple scalars and nonconserved scalars is briefly discussed.
Simulation of three-dimensional flow around a square cylinder at moderate Reynolds numbers
Authors: Sohankar Ahmad , Norberg C. , Davidson L.
Published: July 2002

Direct numerical simulations of two-dimensional (2D) and 3-D unsteady flow around a square cylinder for moderate Reynolds numbers (Re=150–500) are performed, employing an implicit fractional step method finite-volume code with second-order accuracy in space and time. The simulations, which are carried out with a blockage ratio of 5.6%, indicate a transition from 2-D to 3-D shedding flow between Re=150 and Re=200. Both spanwise instability modes, A and B, are present in the wake transitional process, similar to the flow around a circular cylinder. However, seemingly in contrast to a circular cylinder, the transitional flow around a square cylinder exhibits a phenomenon of distinct low-frequency force pulsations (Re=200–300). For 3-D simulations, the Strouhal number and the mean drag coefficient are in general agreement with existing experiments. Between Re=300 and 500, an increase in the spanwise coupling of fluctuating forces is indicated. The influence of the spanwise aspect ratio using periodic boundary conditions, a finer grid, and a finer time step is also investigated.
A mechanistic model for shock initiation of solid explosives
Authors: Massoni J. , Saurel R. , Baudin G. , Demol G.
Published: July 2002

This paper is devoted to the building of a model for the ignition and growth of a detonation in pressed solid explosives. The ignition model describes the various phenomena occurring at the microscopic scale during viscoplastic pore collapse. The growth stage is represented by a model combining inner combustion inside the pores and outer combustion on the surface of the grains. These microscopic models are incorporated into a macroscopic one. The macroscopic model reproduces waves propagation and takes into account the various couplings between the microscopic and macroscopic scales. Pores and grain size distributions are also considered. The governing equations are solved using a shock tracking high resolution scheme, in order to avoid numerical smearing of the shock front. The role of microscopic topology of the explosive is investigated. Results are validated on pressure gauge records and shock to detonation transition distance (Pop-plots).
Nonlinear dynamics of irradiated thin volatile liquid films
Authors: Oron Alexander
Published: July 2002

The dynamics of irradiated volatile thin liquid films is studied in the framework of long-wave theory. Strongly nonlinear evolution equations describing the spatio-temporal dynamics of the film in both the optically thin and thick cases are derived. Various kinds of time-dependent base states are found and their linear stability is considered using the quasi-steady method. The results of the numerical study of the governing evolution equations support the results of the linear analysis. It is found that irradiation can partially suppress the growth of the interfacial disturbance. The nonlinear effects accelerate the film rupture with respect to the disappearance time of the corresponding base state. The film rupture time is found to decrease with the intensity of irradiation.
Pore-scale simulation of dispersion
Authors: Maier Robert S. , Kroll Daniel M. , Bernard Robert S. , Howington Stacy E. , Peters John F. , Davis H. Ted
Published: July 2002

Tracer dispersion has been simulated in three-dimensional models of regular and random sphere packings for a range of Peclet numbers. A random-walk particle-tracking (PT) method was used to simulate tracer movement within pore-scale flow fields computed with the lattice-Boltzmann (LB) method. The simulation results illustrate the time evolution of dispersion, and they corroborate a number of theoretical and empirical results for the scaling of asymptotic longitudinal and transverse dispersion with Peclet number. Comparisons with nuclear magnetic resonance (NMR) spectroscopy experiments show agreement on transient, as well as asymptotic, dispersion rates. These results support both NMR findings that longitudinal dispersion rates are significantly lower than reported in earlier experimental literature, as well as the fact that asymptotic rates are observed in relatively short times by techniques that employ a uniform initial distribution of tracers, like NMR.
Nonlocal electron transport in spherical plasmas
Authors: Bychenkov V. Yu. , Matte J. P. , Johnston T. W.
Published: July 2002

The influence of spherical geometry on nonlocal radial electron heat transport has been studied using perturbation analysis . The nonlocal expression for the radial heat flux is obtained in the limit of large ion charge. The deviation of the spherical nonlocal heat transport from the planar theory has been investigated and it has been found that the space curvature can significantly modify the heat flux compared to the planar result when the delocalization length (that associated with the faster electrons which dominate energy transport) is comparable to the radius.
Dust-acoustic waves in a magnetized dusty plasma
Authors: Salimullah M. , Salahuddin M.
Published: July 2002

The modification and damping of the dust-acoustic wave in a uniformly magnetized dusty plasma have been investigated using the Vlasov-kinetic model for the plasma with dust particles as a third component having average constant charge and mass. It is noticed that for the strong finite Larmor radius (FLR) effect, the frequency and damping of the mode depend significantly on the magnetic field and they are independent of the magnetic field for the case of weak FLR effect. For exact transverse propagation (k‖=0), the dust-acoustic mode ceases to exist, however, a new mode known as the “dust-lower-hybrid” mode comes into play in the hot magnetized dusty plasma.
Direct-drive laser fusion: Status and prospects
Authors: Bodner Stephen E. , Colombant Denis G. , Gardner John H. , Lehmberg Robert H. , Obenschain Stephen P. , Phillips Lee , Schmitt Andrew J. , Sethian John D. , McCrory Robert L. , Seka Wolf , Verdon Charles P. , Knauer James P. , Afeyan Bedros B. , Powell Howard T.
Published: July 2002

Techniques have been developed to improve the uniformity of the laser focal profile, to reduce the ablative Rayleigh–Taylor instability, and to suppress the various laser–plasma instabilities. There are now three direct-drive ignition target designs that utilize these techniques. An evaluation of these designs is still ongoing. Some of them may achieve the gains above 100 that are necessary for a fusion reactor. Two laser systems have been proposed that may meet all of the requirements for a fusion reactor.
Improved Ohmic confinement induced by multipulse turbulent heating in the Hefei Tokamak-6M
Authors: Xu Yuhong , Yu Chang-Xuan , Luo J. R. , Mao J. S. , Liu B. H. , Li J. G. , Liang Y. F. , Jie Y. X. , Wu Z. W.
Published: July 2002

The improved Ohmic confinement phase (H-mode) has been observed during the turbulent heating (TH) pulse on the Hefei Tokamak-6M (HT-6M) [World Survey of Activities in Controlled Fusion Research, Nuclear Fusion Special Supplement (International Atomic Energy Agency, Vienna, 1991), p. 190]. The electron temperature and density profiles become steeper, and a more negative radial electric field Er well is developed across the normal Ohmic phase (L-mode) to H-mode transition, at the plasma edge. The edge toroidal and poloidal velocities υφ and υθ and the main ion pressure gradient ∇Pi are substantially enhanced after the TH pulse. It is found that across the transition, υθ, υφ and ∇Pi all play significant roles for regulating the Er profile, and the negative well shape of Er in the H-mode is dominantly maintained by the poloidal rotation. The time evolution indicates that prior to the transition υθ plays a key role in inducing the rapid variations of the Er and its shear. The density fluctuation suppression is independent of the sign of the Er shear(Er′) and Er curvature (Er″) and consistent with the theoretical models of Shaing et al. and Zhang and Mahajan, while the Er″ sign has an appreciable effect on the suppression of the plasma potential fluctuations. This fact reveals that the dependence of these two fluctuation suppressions on the Er shear are different, suggesting that the existing L→H transition theories which consider only a single fluctuating field should be improved.
Effect of magnetic and electrostatic fluctuations on the runaway electron dynamics in tokamak plasmas
Authors: Martín-Solís J. R. , Sánchez R. , Esposito B.
Published: July 2002

A test particle description of the runaway dynamics [J.R. Martín-Solís et al., Phys. Plasmas 5, 2370 (1998)] is extended to investigate the behavior of runaway electrons in the presence of fluctuations of electric and magnetic fields. The interaction with the fluctuations is accounted for via a friction force with an effective “collision” frequency determined by the fluctuation induced radial diffusion coefficient. It is shown that both the runaway generation process and the maximum runaway energy can be noticeably affected by magnetic fluctuations. The test particle model is then used to discuss a proposed runaway control scheme via induced magnetic turbulence, with particular emphasis to situations like major disruptions, where a large number of runaway electrons and high runaway energies are expected. It is found that the efficiency of such scheme can in some cases be jeopardized by drift orbit effects as well as by the coexistence of stochastic magnetic regions with good magnetic surfaces.
Tests of causality: Experimental evidence that sheared E×B flow alters turbulence and transport in tokamaks
Authors: Burrell Keith H.
Published: July 2002

A prime goal in physics research is the development of theories which have the universality needed to explain a wide range of observations. Developed over the past decade, the model of turbulence decorrelation and stabilization by sheared E×B flow has the universality needed to explain the turbulence reduction and confinement improvement seen in the edge and core of a wide range of magnetic confinement devices. Because the E×B shear, turbulence, and transport are all intimately intertwined in multiple feedback loops, devising experiments to test whether E×B shear causes a change in turbulence and transport has been a major challenge for experimentalists. Over the past five years, there have been at least four clear demonstrations of causality performed in tokamak plasmas, both at the plasma edge on Doublet III-D (DIII-D) [Plasma Physics and Controlled Fusion Research 1985 (International Atomic Energy Agency, Vienna, 1986) Vol. I, p.159] and Tokamak Experiment for Technologically Oriented Research (TEXTOR) [Plasma Physics and Controlled Nuclear Fusion Research 1990 (International Atomic Energy Agency, Vienna, 1991) Vol. I, p. 473] and further into the plasma core on DIII-D and Tokamak Fusion Test Reactor [Phys. Plasmas 5, 1577 (1998)]. This paper discusses these tests in detail; the results agree with the expectations from the E×B shear model. This paper also discusses similarities between flow shear effects in plasmas and in neutral fluids and provides examples of flow shear reduction of turbulence in neutral fluids under the proper conditions.
Electron temperature gradient driven turbulence
Authors: Jenko F. , Dorland W. , Kotschenreuther M. , Rogers B. N.
Published: July 2002

Collisionless electron-temperature-gradient-driven (ETG) turbulence in toroidal geometry is studied via nonlinear numerical simulations. To this aim, two massively parallel, fully gyrokinetic Vlasov codes are used, both including electromagnetic effects. Somewhat surprisingly, and unlike in the analogous case of ion-temperature-gradient-driven (ITG) turbulence, we find that the turbulent electron heat flux is significantly underpredicted by simple mixing length estimates in a certain parameter regime (ŝ∼1, low α). This observation is directly linked to the presence of radially highly elongated vortices (“streamers”) which lead to very effective cross-field transport. The simulations therefore indicate that ETG turbulence is likely to be relevant to magnetic confinement fusion experiments.
Quantum capacitance devices
Authors: Luryi Serge
Published: July 2002

Two-dimensional electron gas (2DEG) in a quantum well or inversion layer, unlike an ordinary grounded metallic plane, does not completely screen an applied transverse electric field. Owing to its Fermi degeneracy energy, a 2DEG manifests itself as a capacitor in series, whose capacitance per unit area equals CQ=me2/πℏ2, where m is the effective electron mass in the direction transverse to the quantum well. Partial penetration of an external field through a highly conducting 2DEG allows the implementation of several novel high-speed devices, including a three-terminal resonant-tunneling transistor and a gate-controlled thermionic emission transistor.
A single
Hox3
gene with composite
bicoid
and
zerknüllt
expression characteristics in non-Cyclorrhaphan flies
Authors: Stauber Michael , Prell Alexander , Schmidt-Ott Urs
Published: July 2002

The members of the evolutionarily conserved Hox-gene
complex, termed Hox genes, are required for specifying segmental
identity during embryogenesis in various animal phyla. The
Hox3
genes of winged insects have lost this ancestral
function and are required for the development of extraembryonic
epithelia, which do not contribute to any larval structure. Higher
flies (Cyclorrhapha) such as
Drosophila melanogaster
contain
Hox3
genes of two types, the
zerknüllt
type and the
bicoid
type.
The
zerknüllt
gene is expressed zygotically on the
dorsal side of the embryo and is required for establishing
extraembryonic tissue. Its sister gene
bicoid
is
expressed maternally and the transcripts are localized at the anterior
pole of the mature egg. BICOID protein, which emerges from this
localized source during early development, is required for embryonic
patterning. All known direct
bicoid
homologues are
confined to Cyclorrhaphan flies. Here, we describe
Hox3
genes of the non-Cyclorrhaphan flies
Empis livida
(Empididae),
Haematopota pluvialis
(Tabanidae), and
Clogmia albipunctata
(Psychodidae). The gene sequences
are more similar to
zerknüllt
homologues than to
bicoid
homologues, but they share expression
characteristics of both genes. We propose that an ancestral
Hox3
gene had been duplicated in the stem lineage of
Cyclorrhaphan flies. During evolution, one of the gene copies lost
maternal expression and evolved as
zerknüllt
,
whereas the second copy lost zygotic expression and evolved as
bicoid
. Our finding correlates well with a partial
reduction of
zerknüllt
-dependent extraembryonic
tissue during Dipteran evolution.
Self-assembly properties of a model RING domain
Authors: Kentsis Alex , Gordon Ronald E. , Borden Katherine L. B.
Published: July 2002

RING domains act in a variety of essential cellular processes but have no general function ascribed to them. Here, we observe that purified arenaviral protein Z, constituted almost entirely by its RING domain, self-assembles
in vitro
into spherical structures that resemble functional bodies formed by Z in infected cells. By using a variety of biophysical methods we provide a thermodynamic and kinetic framework for the RING-dependent self-assembly of Z. Assembly appears coupled to substantial conformational reorganization and changes in zinc coordination of site II of the RING. Thus, the rate-limiting nature of conformational reorganization observed in the folding of monomeric proteins can also apply to the assembly of macromolecular scaffolds. These studies describe a unique mechanism of nonfibrillar homogeneous self-assembly and suggest a general function of RINGs in the formation of macromolecular scaffolds that are positioned to integrate biochemical processes in cells.
Effect of a fatty acid synthase inhibitor on food intake and expression of hypothalamic neuropeptides
Authors: Shimokawa Teruhiko , Kumar Monica V. , Lane M. Daniel
Published: July 2002

The fatty acid synthase inhibitor, C75, acts centrally to
reduce food intake and body weight in mice. Here we report the effects
of C75 on the expression of key orexigenic [neuropeptide Y (NPY),
agouti-related protein (AgRP), and melanin-concentrating hormone] and
anorexigenic [pro-opiomelanocortin (POMC) and
cocaine-amphetamine-related transcript (CART)] neuropeptide
messages in the hypothalami of lean and obese
(
ob
/
ob
) mice. In lean mice, C75 rapidly
and almost completely blocked food intake and prevented fasting-induced
up-regulation of hypothalamic AgRP and NPY mRNAs, as well as
down-regulation of CART and POMC mRNAs. Thus, in lean mice C75 seems to
interrupt the fasting-induced signals that activate expression of NPY
and AgRP and suppression of POMC and CART. In obese mice, C75 rapidly
suppressed food intake, reduced body weight, and normalized
obesity-associated hyperglycemia and hyperinsulinemia. Like its effect
in lean mice, C75 prevented the fasting-induced increase of
hypothalamic NPY and AgRP mRNAs in obese mice, but had no effect on the
expression of POMC and CART mRNAs. The suppressive effect of C75 on
food intake in lean mice seems to be mediated both by NPY/AgRP and
POMC/CART neurons, whereas in obese mice the effect seems to be
mediated primarily by NPY/AgRP neurons. In both lean and obese mice,
C75 markedly increased expression of melaninconcentrating hormone
and its receptor in the hypothalamus.
Mariner
-like transposases are widespread and diverse in flowering plants
Authors: Feschotte Cédric , Wessler Susan R.
Published: July 2002

Complete and partial sequences of
mariner
-like elements (MLEs) have been reported for
hundreds of species of animals, but only two have been identified in
plants. On the basis of these two plant MLEs and several related
sequences identified by database searches, plant-specific degenerate
primers were derived and used to amplify a conserved region of MLE
transposase genes from a variety of plant genomes. Positive products
were obtained for 6 dicots and 31 monocots of 54 plant species tested.
Phylogenetic analysis of 68 distinct MLE transposase sequences from 25
grass species is consistent with vertical transmission and rapid
diversification of multiple lineages of transposases. Surprisingly, the
evolution of MLEs in grasses was accompanied by repeated and
independent acquisition of introns in a localized region of the
transposase gene.
Synergy in a medicinal plant: Antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor
Authors: Stermitz Frank R. , Lorenz Peter , Tawara Jeanne N. , Zenewicz Lauren A. , Lewis Kim
Published: July 2002

Multidrug resistance pumps (MDRs) protect microbial cells from both synthetic and natural antimicrobials. Amphipathic cations are preferred substrates of MDRs. Berberine alkaloids, which are cationic antimicrobials produced by a variety of plants, are readily extruded by MDRs. Several
Berberis
medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump of a human pathogen
Staphylococcus aureus
. The inhibitor was identified as 5′-methoxyhydnocarpin (5′-MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5′-MHC is an amphipathic weak acid and is distinctly different from the cationic substrates of NorA. 5′-MHC had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA substrates against
S. aureus
. MDR-dependent efflux of ethidium bromide and berberine from
S. aureus
cells was completely inhibited by 5′-MHC. The level of accumulation of berberine in the cells was increased strongly in the presence of 5′-MHC, indicating that this plant compound effectively disabled the bacterial resistance mechanism against the berberine antimicrobial.
Gene expression analysis in schizophrenia: Reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22
Authors: Mimmack Michael L. , Ryan Margaret , Baba Hajime , Navarro-Ruiz Juani , Iritani Shuji , Faull Richard L. M. , McKenna Peter J. , Jones Peter B. , Arai Heii , Starkey Michael , Emson Piers C. , Bahn Sabine
Published: July 2002

We screened a custom-made candidate gene cDNA array comprising 300 genes. Genes chosen have either been implicated in schizophrenia, make conceptual sense in the light of the current understanding of the disease, or are located on high-susceptibility chromosome locations. The array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control brains revealed robust up-regulation of apolipoprotein L1 (apo L1) by 2.6-fold. The finding was cross-validated in a blinded quantitative PCR study using prefrontal cortex tissue from the Stanley Foundation brain collection, Bethesda, MD. This collection consists of 15 schizophrenia, 15 bipolar disorder, 15 major depression, and 15 control individuals, all 60 brains being well-matched on conventional parameters, with antipsychotic drug exposure in the schizophrenia and bipolar disorder groups. Significant up-regulation of apo L1 gene expression in schizophrenia was confirmed. Using quantitative PCR, expression profiles of other members of the apo L family (apo L2–L6) were investigated, showing that apo L2 and L4 were highly significantly up-regulated in schizophrenia. Results were then confirmed in an independent set of 20 schizophrenia and 20 control brains from Japan and New Zealand. Apo L proteins belong to the group of high density lipoproteins, with all six apo L genes located in close proximity to each other on chromosome 22q12, a confirmed high-susceptibility locus for schizophrenia and close to the region associated with velocardiofacial syndrome that includes symptoms of schizophrenia.
Resistance to
Ralstonia solanacearum
in
Arabidopsis thaliana
is conferred by the recessive
RRS1-R
gene, a member of a novel family of resistance genes
Authors: Deslandes Laurent , Olivier Jocelyne , Theulières Frédéric , Hirsch Judith , Feng Dong Xin , Bittner-Eddy Peter , Beynon Jim , Marco Yves
Published: July 2002

The identification of two
Arabidopsis thaliana
genes involved in determining recessive resistance to several strains of the causal agent of bacterial wilt,
Ralstonia solanacearum
, is reported. Dominant (
RRS1-S
) and recessive (
RRS1-R
) alleles from susceptible and resistant accessions encode highly similar predicted proteins differing in length and which present a novel structure combining domains found in plant Toll-IL-1 receptor–nucleotide binding site–leucin-rich repeat resistance proteins and a WRKY motif characteristic of some plant transcriptional factors. Although genetically defined as a recessive allele,
RRS1-R
behaves as a dominant resistance gene in transgenic plants. Sequence analysis of the
RRS1
genes present in two homozygous intragenic recombinant lines indicates that several domains of RRS1-R are essential for its resistance function. Additionally,
RRS1-R
-mediated resistance is partially salicylic acid- and NDR1-dependent, suggesting the existence of similar signaling pathways to those controlled by resistance genes in specific resistance.
Structure of adenylylsulfate reductase from the hyperthermophilic
Archaeoglobus fulgidus
at 1.6-Å resolution
Authors: Fritz Günter , Roth Annette , Schiffer Alexander , Büchert Thomas , Bourenkov Gleb , Bartunik Hans D. , Huber Harald , Stetter Karl O. , Kroneck Peter M. H. , Ermler Ulrich
Published: July 2002

The iron-sulfur flavoenzyme adenylylsulfate (adenosine 5′-phosphosulfate, APS) reductase catalyzes reversibly the reduction of APS to sulfite and AMP. The structures of APS reductase from the hyperthermophilic
Archaeoglobus fulgidus
in the two-electron reduced state and with sulfite bound to FAD are reported at 1.6- and 2.5-Å resolution, respectively. The FAD-sulfite adduct was detected after soaking the crystals with APS. This finding and the architecture of the active site strongly suggest that catalysis involves a nucleophilic attack of the N5 atom of reduced FAD on the sulfur atom of APS. In view of the high degree of similarity between APS reductase and fumarate reductase especially with regard to the FAD-binding α-subunit, it is proposed that both subunits originate from a common ancestor resembling archaeal APS reductase. The two electrons required for APS reduction are transferred via two [4Fe-4S] clusters from the surface of the protein to FAD. The exceptionally large difference in reduction potential of these clusters (−60 and −500 mV) can be explained by interactions of the clusters with the protein matrix.
Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups
Authors: Dinkova-Kostova Albena T. , Massiah Michael A. , Bozak Richard E. , Hicks Ronald J. , Talalay Paul
Published: July 2002

Induction of phase 2 enzymes and elevations of glutathione
are major and sufficient strategies for protecting mammals and their
cells against the toxic and carcinogenic effects of electrophiles and
reactive forms of oxygen. Inducers belong to nine chemical classes and
have few common properties except for their ability to modify
sulfhydryl groups by oxidation, reduction, or alkylation. Much evidence
suggests that the cellular “sensor” molecule that recognizes the
inducers and signals the enhanced transcription of phase 2 genes does
so by virtue of unique and highly reactive sulfhydryl functions that
recognize and covalently react with the inducers. Benzylidene-alkanones
and -cycloalkanones are Michael reaction acceptors whose inducer
potency is profoundly increased by the presence of
ortho-
(but not other) hydroxyl substituent(s) on the
aromatic ring(s). This enhancement correlates with more rapid
reactivity of the
ortho
-hydroxylated derivatives with
model sulfhydryl compounds. Proton NMR spectroscopy provides no
evidence for increased electrophilicity of the β-vinyl carbons (the
presumed site of nucleophilic attack) on the hydroxylated inducers.
Surprisingly, these
ortho
-hydroxyl groups display a
propensity for extensive intermolecular hydrogen bond formation, which
may raise the reactivity and facilitate addition of mercaptans, thereby
raising inducer potencies.
The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines
Authors: Leoni Flavio , Zaliani Andrea , Bertolini Giorgio , Porro Giulia , Pagani Paolo , Pozzi Pietro , Donà Giancarlo , Fossati Gianluca , Sozzani Silvano , Azam Tania , Bufler Philip , Fantuzzi Giamila , Goncharov Igor , Kim Soo-Hyun , Pomerantz Benjamin J. , Reznikov Leonid L. , Siegmund Britta , Dinarello Charles A. , Mascagni Paolo
Published: July 2002

Suberoylanilide hydroxamic acid (SAHA) is a hydroxamic acid-containing hybrid polar molecule; SAHA specifically binds to and inhibits the activity of histone deacetylase. Although SAHA, like other inhibitors of histone deacetylase, exhibits antitumor effects by increasing expression of genes regulating tumor survival, we found that SAHA reduces the production of proinflammatory cytokines
in vivo
and
in vitro
. A single oral administration of SAHA to mice dose-dependently reduced circulating TNF-α, IL-1-β, IL-6, and IFN-γ induced by lipopolysaccharide (LPS). Administration of SAHA also reduced hepatic cellular injury in mice following i.v. injection of Con A. SAHA inhibited nitric oxide release in mouse macrophages stimulated by the combination of TNF-α plus IFN-γ. Human peripheral blood mononuclear cells stimulated with LPS in the presence of SAHA released less TNF-α, IL-1-β, IL-12, and IFN-γ (50% reduction at 100–200 nM). The production of IFN-γ stimulated by IL-18 plus IL-12 was also inhibited by SAHA (85% at 200 nM). However, SAHA did not affect LPS-induced synthesis of the IL-1-β precursor, the IL-1 receptor antagonist, or the chemokine IL-8. In addition, IFN-γ induced by anti-CD3 was not suppressed by SAHA. Steady-state mRNA levels for LPS-induced TNF-α and IFN-γ in peripheral blood mononuclear cells were markedly decreased, whereas IL-8 and IL-1-β mRNA levels were unaffected. Because SAHA exhibits antiinflammatory properties
in vivo
and
in vitro
, inhibitors of histone deacetylase may stimulate the expression of genes that control the synthesis of cytokines and nitric oxide or hyperacetylate other targets.
Sexual selection driving diversification in jumping spiders
Authors: Masta Susan E. , Maddison Wayne P.
Published: July 2002

Theory predicts that speciation rates should be accelerated in organisms undergoing sexual selection. In systems involving female choice, sexual selection acts directly on traits that may be important in prezygotic reproductive isolation, potentially fostering rapid divergence of such traits among allopatric populations. Despite the appeal of this concept, it has proven difficult to document. We provide genetic, behavioral, and simulation data illustrating that the striking and possibly recent divergence in traits of male behavior and morphology among populations of the jumping spider
Habronattus pugillis
can be attributed to sexual selection. We have found evidence for varying degrees of lower female response and offspring viability among some between-population crosses, consistent with the early stages of speciation. We have developed a gene-tree-based method for comparing phenotypic and genetic data sets to infer selection, and have found robust statistical evidence that directional selection has acted on male traits, by confirming that their rate of fixation exceeds that of neutral mitochondrial genes. Because these traits are apparent targets of female choice, the results indicate that sexual selection is driving divergence of phenotypes potentially crucial to the speciation process.
Algal blooms reduce the uptake of toxic methylmercury in freshwater food webs
Authors: Pickhardt Paul C. , Folt Carol L. , Chen Celia Y. , Klaue Bjoern , Blum Joel D.
Published: July 2002

Mercury accumulation in fish is a global public health concern, because fish are the primary source of toxic methylmercury to humans. Fish from all lakes do not pose the same level of risk to consumers. One of the most intriguing patterns is that potentially dangerous mercury concentrations can be found in fish from clear, oligotrophic lakes whereas fish from greener, eutrophic lakes often carry less mercury. In this study, we experimentally tested the hypothesis that increasing algal biomass reduces mercury accumulation at higher trophic levels through the dilution of mercury in consumed algal cells. Under bloom dilution, as algal biomass increases, the concentration of mercury per cell decreases, resulting in a lower dietary input to grazers and reduced bioaccumulation in algal-rich eutrophic systems. To test this hypothesis, we added enriched stable isotopes of Hg to experimental mesocosms and measured the uptake of toxic methylmercury (CH
3
200
Hg
+
) and inorganic
201
Hg
2+
by biota at several algal concentrations. We reduced absolute spike detection limits by 50–100 times compared with previous techniques, which allowed us to conduct experiments at the extremely low aqueous Hg concentrations that are typical of natural systems. We found that increasing algae reduced CH
3
Hg
+
concentrations in zooplankton 2–3-fold. Bloom dilution may provide a mechanistic explanation for lower CH
3
Hg
+
accumulation by zooplankton and fish in algal-rich relative to algal-poor systems.
Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
Authors: Read Martin , Harrison R. John , Romagnoli Barbara , Tanious Farial A. , Gowan Sharon H. , Reszka Anthony P. , Wilson W. David , Kelland Lloyd R. , Neidle Stephen
Published: July 2002

The telomerase enzyme is a potential therapeutic target in
many human cancers. A series of potent inhibitors has been designed by
computer modeling, which exploit the unique structural features of
quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are
predicted to interact selectively with the human DNA quadruplex
structure, as a means of specifically inhibiting the action of human
telomerase in extending the length of single-stranded telomeric DNA.
The anilino substituent at the 9-position of the acridine chromophore
is predicted to lie in a third groove of the quadruplex. Calculated
relative binding energies predict enhanced selectivity compared with
earlier 3,6-disubstituted compounds, as a result of this substituent.
The ranking order of energies is in accord with equilibrium binding
constants for quadruplex measured by surface plasmon resonance
techniques, which also show reduced duplex binding compared with the
disubstituted compounds. The 3,6,9-trisubstututed acridines have potent
in vitro
inhibitory activity against human telomerase,
with EC
50
values of up to 60 nM.
Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone
Authors: Sack John S. , Kish Kevin F. , Wang Chihuei , Attar Ricardo M. , Kiefer Susan E. , An Yongmi , Wu Ginger Y. , Scheffler Julie E. , Salvati Mark E. , Krystek Stanley R. , Weinmann Roberto , Einspahr Howard M.
Published: July 2002

The structures of the ligand-binding domains (LBD) of the wild-type
androgen receptor (AR) and the T877A mutant corresponding to that in
LNCaP cells, both bound to dihydrotestosterone, have been refined at
2.0 Å resolution. In contrast to the homodimer seen in the retinoid-X
receptor and estrogen receptor LBD structures, the AR LBD is monomeric,
possibly because of the extended C terminus of AR, which lies in a
groove at the dimerization interface. Binding of the natural ligand
dihydrotestosterone by the mutant LBD involves interactions with the
same residues as in the wild-type receptor, with the exception of the
side chain of threonine 877, which is an alanine residue in the mutant.
This structural difference in the binding pocket can explain the
ability of the mutant AR found in LNCaP cells (T877A) to accommodate
progesterone and other ligands that the wild-type receptor cannot.
Fast methods for the Eikonal and related Hamilton– Jacobi equations on unstructured meshes
Authors: Sethian J. A. , Vladimirsky A.
Published: July 2002

The Fast Marching Method is a numerical algorithm for solving the Eikonal equation on a rectangular orthogonal mesh in
O
(
M
log
M
) steps, where
M
is the total number of grid points. The scheme relies on an upwind finite difference approximation to the gradient and a resulting causality relationship that lends itself to a Dijkstra-like programming approach. In this paper, we discuss several extensions to this technique, including higher order versions on unstructured meshes in

R
n

and on manifolds and connections to more general static Hamilton–Jacobi equations.
The
P450–1
gene of
Gibberella fujikuroi
encodes a multifunctional enzyme in gibberellin biosynthesis
Authors: Rojas María Cecilia , Hedden Peter , Gaskin Paul , Tudzynski Bettina
Published: July 2002

Recent studies have shown that the genes of the gibberellin (GA)
biosynthesis pathway in the fungus
Gibberella fujikuroi
are organized in a cluster of at least seven genes.
P450–1
is one of four cytochrome
P450
monooxygenase genes in this cluster. Disruption of the
P450–1
gene in the GA-producing wild-type strain IMI
58289 led to total loss of GA production. Analysis of the
P450–1
-disrupted mutants indicated that GA biosynthesis
was blocked immediately after
ent
-kaurenoic acid. The
function of the
P450–1
gene product was investigated
further by inserting the gene into mutants of
G.
fujikuroi
that lack the entire GA gene cluster; the gene was
highly expressed under GA production conditions in the absence of the
other GA-biosynthesis genes. Cultures of transformants containing
P450–1
converted
ent
-[
14
C]kaurenoic acid efficiently into
[
14
C]GA
14
, indicating that P450–1 catalyzes
four sequential steps in the GA-biosynthetic pathway:
7β-hydroxylation, contraction of ring B by oxidation at C-6,
3β-hydroxylation, and oxidation at C-7. The GA precursors
ent-
7α-hydroxy[
14
C]kaurenoic acid,
[
14
C]GA
12
-aldehyde, and
[
14
C]GA
12
were also converted to
[
14
C]GA
14
. In addition, there is an
indication that P450–1 may also be involved in the formation of the
kaurenolides and fujenoic acids, which are by-products of GA
biosynthesis in
G. fujikuroi
. Thus, P450–1 displays
remarkable multifunctionality and may be responsible for the formation
of 12 products.
Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Mérino ewes
Authors: Mulsant Philippe , Lecerf Frédéric , Fabre Stéphane , Schibler Laurent , Monget Philippe , Lanneluc Isabelle , Pisselet Claudine , Riquet Juliette , Monniaux Danielle , Callebaut Isabelle , Cribiu Edmond , Thimonier Jacques , Teyssier Jacques , Bodin Loys , Cognié Yves , Chitour Nour , Elsen Jean-Michel
Published: July 2002

Ewes from the Booroola strain of Australian Mérino sheep are
characterized by high ovulation rate and litter size. This phenotype is
due to the action of the
FecB

B

allele of a major gene named
FecB
, as
determined by statistical analysis of phenotypic data. By genetic
analysis of 31 informative half-sib families from heterozygous sires,
we showed that the
FecB
locus is situated in the region
of ovine chromosome 6 corresponding to the human chromosome 4q22–23
that contains the bone morphogenetic protein receptor IB
(
BMPR-IB
) gene encoding a member of the transforming
growth factor-β (TGF-β) receptor family. A nonconservative
substitution (Q249R) in the
BMPR-IB
coding sequence was
found to be associated fully with the hyperprolificacy phenotype of
Booroola ewes.
In vitro
, ovarian granulosa cells from
FecB

B

/
FecB

B

ewes were less responsive than granulosa cells from
FecB
+
/
FecB
+
ewes to the inhibitory effect on steroidogenesis of GDF-5 and BMP-4,
natural ligands of BMPR-IB. It is suggested that in
FecB

B

/
FecB

B

ewes, BMPR-IB would be inactivated partially, leading to an advanced
differentiation of granulosa cells and an advanced maturation of
ovulatory follicles.
BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma
Authors: Loukinov Dmitri I. , Pugacheva Elena , Vatolin Sergei , Pack Svetlana D. , Moon Hanlim , Chernukhin Igor , Mannan Poonam , Larsson Erik , Kanduri Chandrasekhar , Vostrov Alexander A. , Cui Hengmi , Niemitz Emily L. , Rasko John E. J. , Docquier France M. , Kistler Malathi , Breen Joseph J. , Zhuang Zhengping , Quitschke Wolfgang W. , Renkawitz Rainer , Klenova Elena M. , Feinberg Andrew P. , Ohlsson Rolf , Morse Herbert C. , Lobanenkov Victor V.
Published: July 2002

CTCF, a conserved, ubiquitous, and highly versatile 11-zinc-finger factor involved in various aspects of gene regulation, forms methylation-sensitive insulators that regulate X chromosome inactivation and expression of imprinted genes. We document here the existence of a paralogous gene with the same exons encoding the 11-zinc-finger domain as mammalian
CTCF
genes and thus the same DNA-binding potential, but with distinct amino and carboxy termini. We named this gene
BORIS
for
B
rother
o
f the
R
egulator of
I
mprinted
S
ites. BORIS is present only in the testis, and expressed in a mutually exclusive manner with CTCF during male germ cell development. We show here that erasure of methylation marks during male germ-line development is associated with dramatic up-regulation of
BORIS
and down-regulation of
CTCF
expression. Because BORIS bears the same DNA-binding domain that CTCF employs for recognition of methylation marks in soma, BORIS is a candidate protein for the elusive epigenetic reprogramming factor acting in the male germ line.
A DNA transfection system for generation of influenza A virus from eight plasmids
Authors: Hoffmann Erich , Neumann Gabriele , Kawaoka Yoshihiro , Hobom Gerd , Webster Robert G.
Published: July 2002

We have developed an eight-plasmid DNA transfection system for the rescue of infectious influenza A virus from cloned cDNA. In this plasmid-based expression system, viral cDNA is inserted between the RNA polymerase I (pol I) promoter and terminator sequences. This entire pol I transcription unit is flanked by an RNA polymerase II (pol II) promoter and a polyadenylation site. The orientation of the two transcription units allows the synthesis of negative-sense viral RNA and positive-sense mRNA from one viral cDNA template. This pol I–pol II system starts with the initiation of transcription of the two cellular RNA polymerase enzymes from their own promoters, presumably in different compartments of the nucleus. The interaction of all molecules derived from the cellular and viral transcription and translation machinery results in the generation of infectious influenza A virus. The utility of this system is proved by the recovery of the two influenza A viruses: A/WSN/33 (H1N1) and A/Teal/HK/W312/97 (H6N1). Seventy-two hours after the transfection of eight expression plasmids into cocultured 293T and MDCK cells, the virus yield in the supernatant of the transfected cells was between 2 × 10
5
and 2 × 10
7
infectious viruses per milliliter. We also used this eight-plasmid system for the generation of single and quadruple reassortant viruses between A/Teal/HK/W312/97 (H6N1) and A/WSN/33 (H1N1). Because the pol I–pol II system facilitates the design and recovery of both recombinant and reassortant influenza A viruses, it may also be applicable to the recovery of other RNA viruses entirely from cloned cDNA.
The O-GlcNAc transferase gene resides on the X chromosome and is essential for embryonic stem cell viability and mouse ontogeny
Authors: Shafi Raheel , Iyer Sai Prasad N. , Ellies Lesley G. , O'Donnell Niall , Marek Kurt W. , Chui Daniel , Hart Gerald W. , Marth Jamey D.
Published: July 2002

Nuclear and cytoplasmic protein glycosylation is a widespread and reversible posttranslational modification in eukaryotic cells. Intracellular glycosylation by the addition of
N-
acetylglucosamine (GlcNAc) to serine and threonine is catalyzed by the O-GlcNAc transferase (OGT). This “O-GlcNAcylation” of intracellular proteins can occur on phosphorylation sites, and has been implicated in controlling gene transcription, neurofilament assembly, and the emergence of diabetes and neurologic disease. To study OGT function
in vivo
, we have used gene-targeting approaches in male embryonic stem cells. We find that OGT mutagenesis requires a strategy that retains an intact
OGT
gene as accomplished by using Cre-loxP recombination, because a deletion in the
OGT
gene results in loss of embryonic stem cell viability. A single copy of the
OGT
gene is present in the male genome and resides on the X chromosome near the centromere in region D in the mouse spanning markers
DxMit41
and
DxMit95
, and in humans at Xq13, a region associated with neurologic disease. OGT RNA expression in mice is comparably high among most cell types, with lower levels in the pancreas. Segregation of
OGT
alleles in the mouse germ line with ZP3-Cre recombination in oocytes reveals that intact
OGT
alleles are required for completion of embryogenesis. These studies illustrate the necessity of conditional gene-targeting approaches in the mutagenesis and study of essential sex-linked genes, and indicate that OGT participation in intracellular glycosylation is essential for embryonic stem cell viability and for mouse ontogeny.
Gamma and beta frequency oscillations in response to novel auditory stimuli: A comparison of human electroencephalogram (EEG) data with
in vitro
models
Authors: Haenschel Corinna , Baldeweg Torsten , Croft Rodney J. , Whittington Miles , Gruzelier John
Published: July 2002

Investigations using hippocampal slices maintained
in vitro
have demonstrated that bursts of oscillatory field potentials in the gamma frequency range (30–80 Hz) are followed by a slower oscillation in the beta 1 range (12–20 Hz). In this study, we demonstrate that a comparable gamma-to-beta transition is seen in the human electroencephalogram (EEG) in response to novel auditory stimuli. Correlations between gamma and beta 1 activity revealed a high degree of interdependence of synchronized oscillations in these bands in the human EEG. Evoked (stimulus-locked) gamma oscillations preceded beta 1 oscillations in response to novel stimuli, suggesting that this may be analogous to the gamma-to-beta shift observed
in vitro
. Beta 1 oscillations were the earliest discriminatory responses to show enhancement to novel stimuli, preceding changes in the broad-band event-related potential (mismatch negativity). Later peaks of induced beta activity over the parietal cortex were always accompanied by an underlying gamma frequency oscillation as seen
in vitro.
A further analogy between
in vitro
and human recordings was that both gamma and beta oscillations habituated markedly after the initial novel stimulus presentation.
Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments
Authors: Alonso Alejandra del C. , Zaidi Tanweer , Novak Michal , Grundke-Iqbal Inge , Iqbal Khalid
Published: July 2002

The microtubule-associated protein τ is a family of six isoforms
that becomes abnormally hyperphosphorylated and accumulates in the form
of paired helical filaments (PHF) in the brains of patients with
Alzheimer's disease (AD) and patients with several other tauopathies.
Here, we show that the abnormally hyperphosphorylated τ from AD brain
cytosol (AD P-τ) self-aggregates into PHF-like structures on
incubation at pH 6.9 under reducing conditions at 35°C during 90 min.
In vitro
dephosphorylation, but not deglycosylation, of
AD P-τ inhibits its self-association into PHF. Furthermore,
hyperphosphorylation induces self-assembly of each of the six τ
isoforms into tangles of PHF and straight filaments, and the
microtubule binding domains/repeats region in the absence of the rest
of the molecule can also self-assemble into PHF. Thus, it appears that
τ self-assembles by association of the microtubule binding
domains/repeats and that the abnormal hyperphosphorylation promotes
the self-assembly of τ into tangles of PHF and straight filaments by
neutralizing the inhibitory basic charges of the flanking regions.