bluuebunny/crossref_metadata_2025 huggingface dataset:
The asymptotic behavior of the stochastic Ginzburg–Landau equation with multiplicative noise
Authors: Desheng Yang
Published: October 2004

The asymptotic behavior of the stochastic Ginzburg–Landau equation is studied. We obtain the stochastic Ginzburg–Landau equation as a finite-dimensional random attractor.
Internal probe array for the measurement of radial electric field
Authors: Andreason Samuel P. , Slough John T.
Published: October 2004

A multipoint radial electric field probe, paired with a Langmuir triple probe has been operated on a RF sustained field reversed configuration. Langmuir probe measurements confirm the approximation that Te(r)∼constant, allowing for simpler interpretation of the floating potential, and the probe array was implemented with nonemissive, floating probes. Due to the large antenna potentials (multi-kilovolts), the electric field probe was designed taking advantage of the development of inexpensive, multichannel, portable digital storage oscilloscopes. This also made it possible to operate the internal plasma diagnostic with a minimum of electrical design work and fewer calibration issues. The diagnostic was electrically isolated (floated) separate from experiment ground, and has been used to measure transient electric fields as large as 2.5 kV/m.
Efficient electron beam deposition in the gas cell of the Electra laser
Authors: Hegeler F. , Rose D. V. , Myers M. C. , Sethian J. D. , Giuliani J. L. , Wolford M. F. , Friedman M.
Published: October 2004

Extensive research has been performed to elucidate the transport of electron beam energy from a vacuum diode, through a foil support structure (hibachi), and into the Electra laser cell. Measurements and simulations of the energy deposition in the cell are reported for various krypton/argon mixtures, gas pressures, and the thickness and material of the hibachi foil. Two hibachi and several cathode configurations are investigated and electron energy deposition efficiencies into the gas of up to 75% have been achieved with a 500 kV, 180 ns full width at half maximum diode pulse. The experimental data are compared with one-, two-, and three-dimensional Monte Carlo transport calculations and particle-in-cell simulations. The importance of electron backscattering, radiation effects, and power deposition uniformity in the laser gas are discussed.
On the probability distribution function of particle density at the edge of fusion devices
Authors: Sattin F. , Vianello N. , Valisa M.
Published: October 2004

The probability distribution function Pn(n) of the particle density at the edge of several magnetic fusion devices, including tokamaks, stellarators, and linear devices, is known to be strongly non-Gaussian. In this paper experimental results from RFX reversed field pinch (RFP) [G. Rostagni, Fusion Eng. Des. 25, 301 (1995)] are presented, confirming the universal shape of Pn also for RFP’s. An explanation for the form of Pn is attempted, on the basis of simple conservation equations. The model result is shown to fit fairly well empirical data in a few different experimental scenarios.
Magnetic mirror minimum B field with optimal ellipticity
Authors: Ågren O. , Savenko N.
Published: October 2004

Closed form expressions for the ellipticity and the magnetic field of a conventional mirror machine, constrained to fulfill a minimum B stability criterion, are derived. The best result for zero-β plasmas is obtained with a marginally stable magnetic field, and the ellipticity is 13.9 with the representative value 4 for the mirror ratio. The gyro centers move on a single filed line, and thereby the perpendicular drift is zero and the radial transport is minimized. The flux tube has quadrupolar symmetry with straight (nonparallel) field lines in the confinement region.
Magnetohydrodynamic equilibrium and stability of rotating plasmas in a mirror geometry
Authors: Aydemir A. Y.
Published: October 2004

A systematic study of equilibrium and stability of rotating plasmas in a mirror geometry is presented. At supersonic azimuthal rotation velocities, centrifugal forces lead to equilibria with nearly detached plasmas, where the plasma mass concentrates at the mirror center. However, isolation of the plasma from the ends is not complete due to high parallel thermal conduction. Temperature remains a flux function, connecting the centrifugally confined region to the end points. Rotation shear is found to be strongly stabilizing for the interchange (flute) modes, as demonstrated in earlier works. However, all configurations studied to date with various rotation profiles are found to be linearly unstable to other ideal magnetohydrodynamic (MHD) modes. Thus, it is unlikely that these centrifugally detached states can be accessed within ideal MHD.
A comparative analysis of the electron energy distribution function obtained by regularization methods and by a least-squares fitting
Authors: Gutiérrez-Tapia César , Flores-LLamas Héctor
Published: October 2004

The second derivative of a Langmuir probe current-voltage (I-V) characteristic is numerically integrated using the Tikhonov singular value decomposition regularized method in order to establish the electron energy distribution function (EEDF). A comparison of the numerically integrated EEDF and a least-squares (LS) fitting is discussed. The I-V characteristic is measured in an electron cyclotron resonance plasma source using a cylindrical probe and the plasma parameters are determined by means of the Laframboise theory. This technique allows a fast analysis of plasma parameters at any gas pressure. In the case of the LS fitting, the results obtained are similar to those from the regularization method but, in the first case, the procedure turns out to be rather slow to reach the better fitting apart from demanding some guess work.
Direct numerical simulation of equilibrium spatially localized structures in pipe flow
Authors: Priymak V. G. , Miyazaki T.
Published: October 2004

The possibility of intermittent turbulent shear flows’ description by means of nonstationary long-wave three-dimensional Navier–Stokes solutions is shown in principle. The classical problem of viscous incompressible fluid flows in a circular pipe at transitional Reynolds numbers 1800⩽Re⩽4000 is taken as a model one. By means of direct numerical simulation statistically stationary Navier–Stokes solutions which describe turbulent (at 2500⩽Re⩽4000), intermittent (at Re=2200,2350), and laminar (Re⩽2000) flow regimes are obtained. Numerical solutions at Re=2200,2350 describe equilibrium self-sustained flow regimes in which turbulent structures surrounded by almost laminar flow propagate downstream while preserving their length. Thus, theoretical confirmation of the existence of particular transitional flow regimes—equilibrium puffs—is achieved. The space-time structure of equilibrium puffs is examined with particular emphasis on flow visualization and calculation of propagation velocities. Basic turbulence statistics inside and outside the puff are computed and compared with the existing experimental data.
Use of the particle image velocimetry technique to study the propagation of second sound shock in superfluid helium
Authors: Zhang T. , Van Sciver S. W.
Published: October 2004

Transient counterflow velocity fields induced by second sound shock in helium II have been measured using the particle image velocimetry (PIV) technique. The arrival of the shock front, passage of the shock tail, and onset of heat diffusion are clearly visualized as velocity profiles of suspended micron-size particles. Measured particle velocities are compared to calculated normal fluid velocities. Other observations include a critical energy flux for the onset of quantum turbulence and random motion of particles behind the shock. These results indicate that PIV may be a useful tool in the study of second sound and superfluid turbulence.
Time-Shrinking: The Process of Unilateral Temporal Assimilation
Authors: Nakajima Yoshitaka , ten Hoopen Gert , Sasaki Takayuki , Yamamoto Katsuyuki , Kadota Masahiro , Simons Michel , Suetomi Daigoh
Published: October 2004

Our previous research on auditory time perception showed that the duration of empty time intervals shorter than about 250 ms can be underestimated hugely if they are immediately preceded by shorter time intervals. We named this illusion ‘time-shrinking’ (TS). This study comprises four experiments in which the preceding interval, t1, was followed by a standard interval, t2. When t1 ⩽ 200 ms, and t1 ⩽ t2, the underestimation of t2 came into view clearly. The absolute difference between t2 and t1 was the crucial factor for the illusion to appear. The underestimation increased when t2 increased from t1 to t1 + 65 ms, stayed at about 45 ms when t2 was between t1 + 65 ms and t1 + 95 ms, and disappeared suddenly when t2 exceeded t1 + 95 ms. This pattern of results was observed across all values of t1 ⩽ 200 ms. A model was fit to the data to elucidate the underlying process of the illusion. The model states that the perceived duration difference between t1 and t2 is reduced by cutting mental processing time for t2; in other words, that t2 assimilates to t1.
The Development of Distance Estimation in Optic Flow
Authors: Baumberger Bernard , Flückiger Michelangelo
Published: October 2004

In three experiments we tested the ability of children aged 8 to 12 years and adults to locate a target in an optic texture flow projected onto the ground. During the exposure phase, a static target (diode) was lit up at 6 m or 8 m on the ground in front of the subject. During the pointing phase, the subject was asked to indicate the perceived location of the target with a laser pointer as soon as the target was switched off. In the first experiment, during both phases the optic texture (environment) was either motionless or approaching the subject. Results showed that target locations were significantly more underestimated within the moving texture than within the still texture. In the second experiment, a detailed error analysis showed that the differences of performance between children and adults were not due to differences in eye height. Errors can be described by a linear fit with the retinal speed of the optic flow surrounding the targets. Distance judgments improved from the age of 8 years onwards. In the last experiment we found the same kind of results with a receding texture and without stimulation in central vision. Results are discussed in terms of subject's capacity to compensate for the effect of linear vection produced by the optic flow.
Experiments with a Hollow Mask and a Reverspective: Top-down Influences in the Inversion Effect for 3-D Stimuli
Authors: Papathomas Thomas V , Bono Lisa M
Published: October 2004

Earlier psychophysical and physiological studies, obtained mostly with two-dimensional (2-D) stimuli, provided evidence for the hypothesis that the processing of faces differs from that of scenes. We report on our experiments, employing realistic three-dimensional (3-D) stimuli of a hollow mask and a scene, that offer further evidence for this hypothesis. The stimuli used for both faces and scenes were bistable, namely they could elicit either the veridical or an illusory volumetric percept. Our results indicate that the illusion is weakened when the stimuli are inverted, suggesting the involvement of top-down processes. This inversion effect is statistically significant for the facial stimulus, but the trend did not reach statistical significance for the scene stimulus. These results support the hypothesis that configural processing is stronger for the 3-D perception of faces than it is for scenes, and extend the conclusions of earlier studies on 2-D stimuli.
Task-Dependent Changes of the Psychophysical Motion-Tuning Functions in the Course of Perceptual Learning
Authors: Koyama Shinichi , Harner Alexander , Watanabe Takeo
Published: October 2004

In some cases, perceptual learning is task-specific. However, task-dependent effects of perceptual learning on psychophysical motion-tuning functions have yet to be clarified. In the present study, subjects performed motion detection or discrimination of the same stimulus over the course of four sessions held on separate days. Subjects who performed motion detection showed the most highly improved performance on the trained motion directions. However, after discrimination training, the highest improvement was not observed at the trained directions but shifted away from them. These results can be explained by lateral inhibition. Task demands may differentially modulate excitatory and inhibitory signals to directions in the vicinity of the trained directions.
A Comparison of Auditory and Visual Apparent Motion Presented Individually and with Crossmodal Moving Distractors
Authors: Strybel Thomas Z , Vatakis Argiro
Published: October 2004

Unimodal auditory and visual apparent motion (AM) and bimodal audiovisual AM were investigated to determine the effects of crossmodal integration on motion perception and direction-of-motion discrimination in each modality. To determine the optimal stimulus onset asynchrony (SOA) ranges for motion perception and direction discrimination, we initially measured unimodal visual and auditory AMs using one of four durations (50, 100, 200, or 400 ms) and ten SOAs (40–450 ms). In the bimodal conditions, auditory and visual AM were measured in the presence of temporally synchronous, spatially displaced distractors that were either congruent (moving in the same direction) or conflicting (moving in the opposite direction) with respect to target motion. Participants reported whether continuous motion was perceived and its direction. With unimodal auditory and visual AM, motion perception was affected differently by stimulus duration and SOA in the two modalities, while the opposite was observed for direction of motion. In the bimodal audiovisual AM condition, discriminating the direction of motion was affected only in the case of an auditory target. The perceived direction of auditory but not visual AM was reduced to chance levels when the crossmodal distractor direction was conflicting. Conversely, motion perception was unaffected by the distractor direction and, in some cases, the mere presence of a distractor facilitated movement perception.
Psychophysics with Junctions in Real Images
Authors: McDermott Josh
Published: October 2004

Junctions, formed at the intersection of image contours, are thought to play an important and early role in vision. The interest in junctions can be attributed in part to the notion that they are local image features that are easy to detect but that nonetheless provide valuable information about important events in the world, such as occlusion and transparency. Here I test the notion that there are locally defined junctions in real images that might be detected with simple, early visual mechanisms. Human observers were used as a tool to measure the visual information available in local regions of real images. One set of observers was made to label all the points in a set of real images where one edge occluded another. A second set of observers was presented with variable-size circular subregions of these images, and was asked to judge whether the regions were centered on an occlusion point. This task is easy if junctions are visible, but I found performance to be poor for small regions, not approaching ceiling levels until observers were given fairly large (∼ 50 pixels in diameter) regions over which to make the judgment. Control experiments ruled out the possibility that the effects are just due to junctions at multiple scales. Experiments reported here suggest that, although some junctions in real images are locally defined and can be detected with simple mechanisms, a substantial fraction necessitate the use of more complex and global processes. This raises the possibility that junctions in such cases may not be detected prior to scene interpretation.
Molecular analysis of a stress-induced cDNA encoding the translation initiation factor, eIF1, from the salt-tolerant wild relative of rice, Porteresia coarctata
Authors: Latha Rangan , Salekdeh G. Hosseini , Bennett John , Swaminathan Monkumbu Sambasivan
Published: October 2004

The analysis of plant response to stress is an important route to the discovery of genes conferring stress tolerance. Protein synthesis is very sensitive to salt stress and proteins involved in this process may be an important determinant of salt tolerance. The halophytic plant, Porteresia coarctata Tateoka, is a close relative of Oryza sativa L., and has the ability to withstand sudden changes in the soil salinity. The translation initiation factor 1 (PceIF1) cDNA was isolated from the leaves of P. coarctata that had been subjected to a high-salt treatment (150 mm NaCl). An expression study showed that the abundance of eIF1 transcripts increased to a maximum level 5 d after stress induction and then decreased to levels similar to leaves of control (unsalinised) plants. This gene was also up-regulated in exogenous abscisic acid (ABA) and mannitol treatments, suggesting that its induction is related to the water deficit effect of high salt. Our studies showed that expression levels of eIF1 transcripts might form a convenient indicator for monitoring a stress-responsive mechanism that operates in the leaves of P. coarctata.
Genetic mapping of basal root gravitropism and phosphorus acquisition efficiency in common bean
Authors: Liao Hong , Yan Xiaolong , Rubio Gerardo , Beebe Steve E. , Blair Matthew W. , Lynch Jonathan P.
Published: October 2004

Root gravitropism determines the relative distribution of plant roots in different soil layers, and therefore, may influence the acquisition of shallow soil resources such as phosphorus (P). Growth pouch and field studies were conducted to evaluate root gravitropism of common bean (Phaseolus vulgaris L.) in response to P deficiency and to detect quantitative trait loci (QTL) associated with this trait. A deep-rooted genotype, DOR364, was crossed with a shallow-rooted genotype, G19833, to obtain 86 F5.7 recombinant inbred lines (RILs). Root gravitropic traits were measured as basal root growth angle (BRGA), shallow basal root length (SBRL, basal root length in the top 0–3 cm of soil) and relative shallow basal root length (RSBRL, percentage of basal root length in the top 0–3 cm of soil relative to total basal root length). Large genetic variability for these traits was found in the parents and RILs, with BRGA ranging from –18.73 to 56.69º and SBRL ranging from 0.42 to 2.63 m per plant. The parents and six RILs with contrasting root gravitropism were further evaluated in the field, where root shallowness was significantly correlated with plant growth and P uptake. QTL were detected by single point analysis (SPA), interval mapping (IM) and composite interval mapping (CIM) techniques with a genetic map for the DOR364 × G19833 population consisting of 236 molecular markers. The IM / CIM QTL were detected among the 11 linkage groups of common bean, with 16 QTL controlling the above root traits and six QTL controlling P acquisition efficiency (PAE) in the field study. At least three of the root trait QTL were associated with QTL for PAE, suggesting that root gravitropic traits are associated with PAE and that QTL for these traits can be used to facilitate selection and breeding for higher P efficiency in common bean and other crops.
Biomass allocation in tomato (Lycopersicon esculentum) plants grown under partial rootzone drying: enhancement of root growth
Authors: Mingo Darren M. , Theobald Julian C. , Bacon Mark A. , Davies William J. , Dodd Ian C.
Published: October 2004

Tomato (Lycopersicon esculentum Mill.) plants were grown in either a glasshouse (GH) or a controlled environment cabinet (CEC) to assess the effects of partial rootzone drying (PRD) on biomass allocation. Control and PRD plants received the same amounts of water. In control plants, water was equally distributed between two compartments of a split-root system. In PRD plants, only one compartment was watered while the other was allowed to dry. At the end of each drying cycle, wet and dry compartments were alternated. In the GH, total biomass did not differ between PRD and control plants after four cycles of PRD, but PRD increased root biomass by 55% as resources were partitioned away from shoot organs. In the CEC, leaf water potential did not differ between treatments at the end of either of two cycles of PRD, but stomatal conductance of PRD plants was 20% less at the end of the first cycle than at the beginning. After two cycles of PRD in the CEC, biomass did not differ between PRD and control plants, but PRD increased root biomass by 19% over the control plants. The promotion of root biomass in PRD plants was associated with the alternation of wet and dry compartments, with increased root biomass occurring in the re-watered compartment after previous exposure to soil drying. Promotion of root biomass in field-grown PRD plants may allow the root system to access resources (water and nutrients) that would otherwise be unavailable to control plants. This may contribute to the ability of PRD plants to maintain similar leaf water potentials to conventionally irrigated plants, even when smaller irrigation volumes are supplied.
Nitrogen source and water regime effects on barley photosynthesis and isotope signature
Authors: Lopes Marta S. , Nogués Salvador , Araus José L.
Published: October 2004

Water stress and nitrogen (N) availability are the main constraints on barley (Hordeum vulgare L.) yield in Mediterranean conditions. Here we studied the combined effects of N source and water regime (WR) on plant growth, photosynthesis and carbon isotope discrimination (Δ13C) in barley grown under controlled conditions. The effects of these conditions on plant N isotope discrimination against the fertiliser (Δ15N) was also examined to assess whether the natural variation in plant N isotope composition is a reliable indicator of N nutrition. Six experimental treatments were established with three nutrient solutions containing ammonium (NH4+), nitrate (NO3–) or a mixture of the two (NH4+ : NO3–), each either well watered or moderately water stressed. The NH4+ : NO3– treatment resulted in the greatest biomass accumulation and photosynthetic capacity in both WRs. The NH4+ plants showed accelerated phenology and depressed growth. They also had the lowest photosynthetic rates in both WRs. This effect was mainly due to stomatal closure, while electron transport and carboxylation capacity of leaves were less affected. Consistent with lower stomatal conductance, leaf Δ13C was lower in plants that received NH4+, indicating higher water use efficiency (WUE) not only when irrigated, but also under water stress. In addition, leaf Δ13C and photosynthetic N use efficiency (PNUE) correlated positively with each other and with shoot biomass in both WRs. However, NO3– treatment produced the greatest Δ15N, which was higher in leaves than in roots. Leaf Δ15N was decreased by water stress only in plants in the NO3– treatment. We conclude that leaf Δ13C is an adequate trait to assess the differences in growth, photosynthetic activity and WUE caused by distinct N sources. However, the usefulness of natural abundance of 15N in plant tissue as a nitrogen source marker is restricted by the effect of WR and internal plant fractionation, at least for plants that received NO3–.
Photosynthetic and antioxidant enzyme responses of sugar maple and red maple seedlings to excess manganese in contrasting light environments
Authors: St. Clair Samuel B. , Lynch Jonathan P.
Published: October 2004

Manganese (Mn) toxicity may be a significant constraint to forest health on acidic, non-glaciated soils. We hypothesised that sugar maple (Acer saccharum Marsh.) and red maple (Acer rubrum L.) seedlings differ in their tolerance to excess Mn, and that photosynthetic sensitivity to excess Mn is exacerbated at higher light intensities through photo-oxidative stress. To test these hypotheses, we assessed photosynthesis and antioxidant enzyme responses of sugar maple and red maple seedlings at variable Mn and light levels in a greenhouse study. In both species, high Mn treatments impaired photosynthetic function, particularly in high light conditions. Responses to Mn and light depended on the developmental stage of the leaves. All sugar maple leaves were sensitive to Mn toxicity except shaded young leaves. For red maple, only mature leaves exposed to high light were prone to Mn toxicity. Antioxidant enzyme and ФPSII / ФCO2 data suggested that photo-oxidative stress did not explain the observed photosynthetic responses to treatment variables. Our results indicate that in natural forest environments, sugar maple and red maple foliage exposed to high light intensity (outer canopy, canopy gaps) may be more prone to Mn toxicity.
Direct measurements of sieve element hydrostatic pressure reveal strong regulation after pathway blockage
Authors: Gould Nick , Minchin Peter E. H. , Thorpe Michael R.
Published: October 2004

According to the Münch hypothesis, solution flow through the phloem is driven by a hydrostatic pressure gradient. At the source, a high hydrostatic pressure is generated in the collection phloem by active loading of solutes, which causes a concomitant passive flow of water, generating a high turgor pressure. At the sink, solute unloading from the phloem keeps the turgor pressure low, generating a source-to-sink hydrostatic pressure gradient. Localised changes in loading and unloading of solutes along the length of the transport phloem can compensate for small, short-term changes in phloem loading at the source, and thus, maintain phloem flow to the sink tissue. We tested directly the hydrostatic pressure regulation of the sieve tube by relating changes in sieve tube hydrostatic pressure to changes in solute flow through the sieve tube. A sudden phloem blockage was induced (by localised chilling of a 1-cm length of stem tissue) while sieve-tube-sap osmotic pressure, sucrose concentration, hydrostatic pressure and flow of recent photosynthate were observed in vivo both upstream and downstream of the block. The results are discussed in relation to the Münch hypothesis of solution flow, sieve tube hydrostatic pressure regulation and the mechanism behind the cold-block phenomenon.
Photosynthetic utilisation of inorganic carbon and its regulation in the marine diatom Skeletonema costatum
Authors: Chen Xiongwen , Gao Kunshan
Published: October 2004

Photosynthetic uptake of inorganic carbon and regulation of photosynthetic CO2 affinity were investigated in Skeletonema costatum (Grev.) Cleve. The pH independence of K1/2(CO2) values indicated that algae grown at either ambient (12 μmol L–1) or low (3 μmol L–1) CO2 predominantly took up CO2 from the medium. The lower pH compensation point (9.12) and insensitivity of photosynthetic rate to di-isothiocyanatostilbene disulfonic acid (DIDS) indicated that the alga had poor capacity for direct HCO3– utilisation. Photosynthetic CO2 affinity is regulated by the concentration of CO2 rather than HCO3–, CO32– or total dissolved inorganic carbon (DIC) in the medium. The response of photosynthetic CO2 affinity to changes in CO2 concentration was most sensitive within the range 3–48 μmol L–1 CO2. Light was required for the induction of photosynthetic CO2 affinity, but not for its repression, when cells were shifted between high (126 μmol L–1) and ambient (12 μmol L–1) CO2. The time needed for cells grown at high CO2 (126 μmol L–1) to fully develop photosynthetic CO2 affinity at ambient CO2 was approximately 2 h, but acclimation to low or very low CO2 levels (3 and 1.3 μmol L–1, respectively) took more than 10 h. Cells grown at low CO2 (3 μmol L–1) required approximately 10 h for repression of all photosynthetic CO2 affinity when transferred to ambient or high CO2 (12 or 126 μmol L–1, respectively), and more than 10 h at very high CO2 (392 μmol L–1).
Estimating genome conservation between crop and model legume species
Authors: Choi Hong-Kyu , Mun Jeong-Hwan , Kim Dong-Jin , Zhu Hongyan , Baek Jong-Min , Mudge Joanne , Roe Bruce , Ellis Noel , Doyle Jeff , Kiss Gyorgy B. , Young Nevin D. , Cook Douglas R.
Published: October 2004

Legumes are simultaneously one of the largest families of crop plants and a cornerstone in the biological nitrogen cycle. We combined molecular and phylogenetic analyses to evaluate genome conservation both within and between the two major clades of crop legumes. Genetic mapping of orthologous genes identifies broad conservation of genome macrostructure, especially within the galegoid legumes, while also highlighting inferred chromosomal rearrangements that may underlie the variation in chromosome number between these species. As a complement to comparative genetic mapping, we compared sequenced regions of the model legume
Medicago truncatula
with those of the diploid
Lotus japonicus
and the polyploid
Glycine max
. High conservation was observed between the genomes of
M. truncatula
and
L. japonicus
, whereas lower levels of conservation were evident between
M. truncatula
and
G. max
. In all cases, conserved genome microstructure was punctuated by significant structural divergence, including frequent insertion/deletion of individual genes or groups of genes and lineage-specific expansion/contraction of gene families. These results suggest that comparative mapping may have considerable utility for basic and applied research in the legumes, although its predictive value is likely to be tempered by phylogenetic distance and genome duplication.
Ceramide, a target for antiretroviral therapy
Authors: Finnegan Catherine M. , Rawat Satinder S. , Puri Anu , Wang Ji Ming , Ruscetti Francis W. , Blumenthal Robert
Published: October 2004

Studies of ceramide metabolism and function in a wide range of biological processes have revealed a role for this lipid in regulating key cellular responses. Our research on the role of sphingolipids in HIV entry has led to the hypothesis that modulation of ceramide levels in target cells affects their susceptibility to HIV infection by rearranging HIV receptors. Cellular ceramide levels were modulated by application of pharmacological agents such as
N
-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide), by treatment with sphingomyelinase (Smase), or by exogenous addition of long-chain ceramide, and determined after metabolic incorporation of [
3
H]sphingosine. Infectivity assays were performed by using a HeLa-derived indicator cell line, TZM-bl, CD4
+
lymphocytes, and monocytes. We observed a dose-dependent inhibition by 4-HPR of infection of TZM-bl cells by a broad range of HIV-1 isolates at low micromolar concentrations with an IC
50
of <1 μM for most isolates tested. Nearly complete inhibition was seen at 5 μM, a dose that enhanced ceramide levels by 50-100%, yet was nontoxic to the cells. Treating cells with other pharmacological agents that enhanced ceramide levels, with Smase, or exogenous addition of long-chain ceramide also resulted in inhibition of HIV-1 infection. Enhancing ceramide levels in CD4
+
lymphocytes and in monocyte-derived macrophages with 4-HPR or Smase significantly reduced infectivity without toxicity. The minimal toxicity of normal cells exposed to 4-HPR should make the drug exceedingly suitable as an anti-HIV therapeutic.
Feeding status and serotonin rapidly and reversibly modulate a
Caenorhabditis elegans
chemosensory circuit
Authors: Chao Michael Y. , Komatsu Hidetoshi , Fukuto Hana S. , Dionne Heather M. , Hart Anne C.
Published: October 2004

Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates and invertebrates. In the nematode
Caenorhabditis elegans
, many behaviors are regulated by 5-HT levels, which are in turn regulated by the presence or absence of food. Here, we show that both food and 5-HT signaling modulate chemosensory avoidance response of octanol in
C. elegans
, and that this modulation is both rapid and reversible. Sensitivity to octanol is decreased when animals are off food or when 5-HT levels are decreased; conversely, sensitivity is increased when animals are on food or have increased 5-HT signaling. Laser microsurgery and behavioral experiments reveal that sensory input from different subsets of octanol-sensing neurons is selectively used, depending on stimulus strength, feeding status, and 5-HT levels. 5-HT directly targets at least one pair of sensory neurons, and 5-HT signaling requires the Gα protein GPA-11. Glutamatergic signaling is required for response to octanol, and the GLR-1 glutamate receptor plays an important role in behavioral response off food but not on food. Our results demonstrate that 5-HT modulation of neuronal activity via G protein signaling underlies behavioral plasticity by rapidly altering the functional circuitry of a chemosensory circuit.
Dissociation of spatial attention and saccade preparation
Authors: Juan Chi-Hung , Shorter-Jacobi Stephanie M. , Schall Jeffrey D.
Published: October 2004

The goal of this experiment was to determine whether the allocation of attention necessarily requires saccade preparation. To dissociate the focus of attention from the endpoint of a saccade, macaque monkeys were trained to perform visual search for a uniquely colored rectangle and shift gaze either toward or opposite this color singleton according to its orientation. A vertical singleton cued a prosaccade, a horizontal singleton, an antisaccade. Saccade preparation was probed by measuring the direction of saccades evoked by intracortical microstimulation of the frontal eye fields at variable times after presentation of the search array. Eye movements evoked on prosaccade trials deviated progressively toward the singleton that was also the endpoint of the correct eye movement. However, eye movements evoked on antisaccade trials never deviated toward the singleton but only progressively toward the location opposite the singleton. This occurred even though previous work showed that on antisaccade trials most neurons in frontal eye fields initially select the singleton while attention is allocated to distinguish its shape. Thus, sensorimotor structures can covertly orient attention without preparing a saccade.
Gene targeting in yeast is initiated by two independent strand invasions
Authors: Langston Lance D. , Symington Lorraine S.
Published: October 2004

To study the mechanism of gene targeting, we examined heteroduplex DNA (hDNA) formation during targeting of two separate chromosomal locations in
Saccharomyces cerevisiae
. We examined both replacement of the entire gene with a heterologous selectable marker and correction of a single base pair insertion mutation by gene targeting, and in all cases our results were consistent with separate strand invasion/resolution at the two ends of the targeting fragment as the dominant mechanism in wild-type cells. A small subset of transformants was consistent with assimilation of a single strand of targeting DNA encompassing both flanking homology regions and the marker into hDNA. hDNA formation during correction of a point mutation by targeted integration was conspicuously altered in a mismatch repair-deficient background and was consistent with single-strand invasion/assimilation without mismatch correction, confirming that gene targeting by this pathway is actively impeded in wild-type yeast. Finally, inversion of one targeted locus and mutation of an active origin of DNA replication at the other locus affected hDNA formation significantly, suggesting that formation of productive interactions between the targeting DNA and the targeted site in the chromosome is sensitive to local DNA dynamics.
Prodrugs of bisthiazolium salts are orally potent antimalarials
Authors: Vial Henri J. , Wein Sharon , Farenc Christine , Kocken Clemens , Nicolas Olivier , Ancelin Marie Laure , Bressolle Francoise , Thomas Alan , Calas Michèle
Published: October 2004

We created neutral antimalarial prodrugs that deliver bisthiazolium compounds with antimalarial activity in the nanomolar range. These drugs primarily affect early intraerythrocytic stages through rapid, nonreversible cytotoxicity. The compounds are suitable for both parenteral and oral use and plasma promotes rapid conversion of the prodrug into the drug. We demonstrate that very low doses offer protection in a murine model of malaria. The drugs show great potential for curing high parasitemia with short-course treatments. Oral administration of the TE3 prodrug completely cures
Plasmodium cynomolgi
infection in rhesus monkeys. The drugs specifically accumulate inside infected erythrocytes, block phosphatidylcholine biosynthesis, and interact with hemozoin. To our knowledge, this class of compounds represents one of the most potent antimalarials tested to date. These unique properties signal a promising future for this class of antimalarial.
A class of eukaryotic GTPase with a punctate distribution suggesting multiple functional replacements of translation elongation factor 1α
Authors: Keeling Patrick J. , Inagaki Yuji
Published: October 2004

Translation elongation factor 1α (EF-1α, or EF-Tu in bacteria) is a highly conserved core component of the translation machinery that is shared by all cellular life. It is part of a large superfamily of GTPases that are involved in translation initiation, elongation, and termination, as well as several other cellular functions. Eukaryotic EF-1α (eEF-1α) is well studied and widely sampled and has been used extensively for phylogenetic analyses. It is generally thought that such highly conserved and functionally integrated proteins are unlikely to be involved in events such as lateral gene transfer or ancient duplication and gene sorting, which would undermine phylogenetic reconstruction. Here we describe a GTPase called EF-like (EFL), which is very similar to, but also distinct from, canonical eEF-1α. EFL is found in a wide variety of eukaryotes (dinoflagellates, haptophytes, cercozoa, green algae, choanoflagellates, and fungi), but its distribution is punctate: organisms that possess EFL are not closely related to one another, and EFL appears to be absent from the closest relatives of organisms that do possess it. Moreover, in most genomes where EFL is present, canonical eEF-1α appears to be absent. Analysis of functional divergence suggests that, whereas EFL is divergent in general, putative functional binding sites involved in translation are not significantly divergent as a whole. Altogether, it appears that EFL has replaced eEF-1α several times independently. This finding could be an indication of an ancient paralogy or, more likely, eukaryote-to-eukaryote lateral gene transfer.
Improvement of comparative model accuracy by free-energy optimization along principal components of natural structural variation
Authors: Qian Bin , Ortiz Angel R. , Baker David
Published: October 2004

Accurate high-resolution refinement of protein structure models is a formidable challenge because of the delicate balance of forces in the native state, the difficulty in sampling the very large number of alternative tightly packed conformations, and the inaccuracies in current force fields. Indeed, energy-based refinement of comparative models generally leads to degradation rather than improvement in model quality, and, hence, most current comparative modeling procedures omit physically based refinement. However, despite their inaccuracies, current force fields do contain information that is orthogonal to the evolutionary information on which comparative models are based, and, hence, refinement might be able to improve comparative models if the space that is sampled is restricted sufficiently so that false attractors are avoided. Here, we use the principal components of the variation of backbone structures within a homologous family to define a small number of evolutionarily favored sampling directions and show that model quality can be improved by energy-based optimization along these directions.
Unveiling functional protein motions with picosecond x-ray crystallography and molecular dynamics simulations
Authors: Hummer Gerhard , Schotte Friedrich , Anfinrud Philip A.
Published: October 2004

A joint analysis of all-atom molecular dynamics (MD) calculations and picosecond time-resolved x-ray structures was performed to gain single-molecule insights into mechanisms of protein function. Ensemble-averaged MD simulations of the L29F mutant of myoglobin after ligand dissociation reproduce the direction, amplitude, and time scales of crystallographically determined structural changes. This close agreement with experiments at comparable resolution in space and time validates the individual MD trajectories. From 1,700 single-molecule trajectories, we identified and structurally characterized a conformational switch that directs dissociated ligands to one of two nearby protein cavities. Subsequent ligand migration proceeds through a network of transiently interconnected internal cavities, with passage between them involving correlated protein–ligand motions. The simulations also suggest how picosecond protein motions modulate the functional dissociation of oxygen and suppress the geminate recombination of toxic carbon monoxide.
Chemical and electrical synapses perform complementary roles in the synchronization of interneuronal networks
Authors: Kopell Nancy , Ermentrout Bard
Published: October 2004

Electrical and chemical synapses exist within the same networks of inhibitory cells, and each kind of synapse is known to be able to foster synchrony among oscillating neurons. Using numerical and analytical techniques, we show here that the electrical and inhibitory coupling play different roles in the synchronization of rhythms in inhibitory networks. The parameter range chosen is motivated by gamma rhythms, in which the γ-aminobutyric acid type A (GABA
A
)-mediated inhibition is relatively strong. Under this condition, addition of a small electrical conductance can increase the degree of synchronization far more than a much larger increase in inhibitory conductance. The inhibitory synapses act to eliminate the effects of different initial conditions, whereas the electrical synapses mitigate suppression of firing due to heterogeneity in the network. Analytical techniques include tracking trajectories of coupled cells between spikes; the analysis shows that, in networks in which the degree of excitability is heterogeneous, inhibition can increase the dispersion of the voltages between spikes, whereas electrical coupling reduces such dispersion.
Proteomic analysis identifies that 14-3-3ζ interacts with β-catenin and facilitates its activation by Akt
Authors: Tian Qiang , Feetham Megan C. , Tao W. Andy , He Xi C. , Li Linheng , Aebersold Ruedi , Hood Leroy
Published: October 2004

β-Catenin is a central effector of Wnt signaling in embryonic and stem cell development and in tumorigenesis. Here, through a mass spectrometric analysis of a β-catenin protein complex, we identified 12 proteins as putative β-catenin interactors. We show that one of them, 14-3-3ζ, enhances β-catenin-dependent transcription by maintaining a high level of β-catenin protein in the cytoplasm. More importantly, 14-3-3ζ facilitates activation of β-catenin by the survival kinase Akt and colocalizes with activated Akt in intestinal stem cells. We propose that Akt phosphorylates β-catenin, which results in 14-3-3ζ binding and stabilization of β-catenin, and these interactions may be involved in stem cell development.
grb2 heterozygosity rescues embryonic lethality but not tumorigenesis in
pten
+/-
mice
Authors: Cully Megan , Elia Andrew , Ong Siew-Hwa , Stambolic Vuk , Pawson Tony , Tsao Ming-Sound , Mak Tak W.
Published: October 2004

PTEN is a tumor suppressor gene implicated in both sporadic cancers and inherited tumor-prone syndromes. Here we show that
pten
+/-
mice display a partially penetrant embryonic lethality. This lethality is associated with defects in both neural and placental development. Notably, this lethality is completely rescued by
grb2
haploinsufficiency. In contrast,
grb2
heterozygosity did not alter tumorigenesis in either
pten
+/-
or T cell-specific
pten
-/-
mice.
grb2
-/hypomorph
murine embryonic fibroblasts (MEFs) show decreased activation of both PKB and Erk upon stimulation with epidermal growth factor, whereas
grb2
-/hypomorph
;
pten
+/-
MEFs activate PKB but not Erk normally. Similarly,
grb2
-/hypomorph
fibroblasts die in low serum, and this phenotype is rescued by
pten
haploinsufficiency. Activation of both PKB and Erk as well as survival in low serum-containing media are all rescued by reexpression of Grb2 containing mutations within the N-terminal Src homology 3 (SH3) domain, but not by C-terminal SH3 domain mutants. The N-terminal SH3 domain mutants fail to bind to Sos, whereas the C-terminal SH3 domain mutants fail to bind to Gab1, suggesting that Erk and PKB activation in fibroblasts in response to epidermal growth factor depends on Gab1 or other C-terminal SH3 domain-interacting proteins, but not on Sos. Thus, PTEN/phosphatidylinositol 3′ kinase signaling requires Grb2 during both embryonic development and fibroblast survival, but Grb2 heterozygosity does not effect tumorigenesis in
pten
-deficient mice. In fibroblasts, survival signals emanating from the epidermal growth factor receptor appear to be PKB-dependent, and this activation depends on the C-terminal SH3 domain of Grb2, likely through the interaction of Grb2 with Gab1.
The polyproline II conformation in short alanine peptides is noncooperative
Authors: Chen Kang , Liu Zhigang , Kallenbach Neville R.
Published: October 2004

The finding that short alanine peptides possess a high fraction of polyproline II (PII) structure (Φ = -75°, Ψ = +145°) at low temperature has broad implications for unfolded states of proteins. An important question concerns whether or not this structure is locally determined or cooperative. We have monitored the conformation of alanine in a series of model peptides AcGG(A)nGGNH
2
(
n
= 1–3) over a temperature range from -10°C to +80°C. Use of
15
N-labeled alanine substitutions makes it possible to measure
3
J
αN
coupling constants accurately over the full temperature range. Based on a 1D next-neighbor model, the cooperative parameter σ of PII nucleation is evaluated from the coupling constant data. The finding that σ is close to unity (1 ± 0.2) indicates a noncooperative role for alanine in PII structure formation, consistent with statistical surveys of the Protein Data Bank that suggest that most PII structure occurs in isolated residues. Lack of cooperativity in these models implies that hydration effects that influence PII conformation in water are highly localized. Using a nuclear Overhauser effect ratio strategy to define the alanine Ψ angle, we estimate that, at 40°C, the time-averaged alanine conformation (Φ = -80°, Ψ = +170°) deviates from canonical PII structure, indicating that PII melts at high temperature. Thus, the high-temperature state of short alanine peptides seems to be an unfolded ensemble with higher distribution in the extended β structure basin, but not a coil.
Default brain functionality in blind people
Authors: Burton H. , Snyder A. Z. , Raichle M. E.
Published: October 2004

We studied whether default functionality of the human brain, as revealed by task-independent decreases in activity occurring during goal-directed behaviors, is functionally reorganized by blindness. Three groups of otherwise normal adults were studied: early blind, adventitiously blind, and normally sighted. They were imaged by using functional MRI during performance of a word association task (verb generation to nouns) administered by using auditory stimuli in all groups and Braille reading in blind participants. In sighted people, this task normally produces robust task-independent decreases relative to a baseline of quiet wakefulness with eyes closed. Our functional MRI results indicate that task-independent decreases are qualitatively similar across all participant groups in medial and dorsal prefrontal, lateral parietal, anterior precuneus, and posterior cingulate cortices. Similarities in task-independent decreases are consistent with the hypothesis that functional reorganization resulting from the absence of a particular sensory modality does not qualitatively affect default functionality as revealed by task-independent decreases. More generally, these results support the notion that the brain largely operates intrinsically, with sensory information modulating rather than determining system operations.