bluuebunny/crossref_metadata_2025 huggingface dataset:
Bifurcation phenomena and the radial electric field in a nonaxisymmetric plasma
Authors: Hastings D. E.
Published: July 2002

The radial electric field in a nonaxisymmetric plasma is known to be a multivalued function of the plasma state. It is shown that the theorem of minimum entropy production rate cannot be used to distinguish between different electric field solutions. The possibility of bifurcation phenomena in the coupled electric field, density, and temperature equations are examined. It is shown that the functional dependence of the plasma source can strongly influence the type of bifurcation that can occur.
Neoclassical transport in stellarators
Authors: Ho Darwin D.-M. , Kulsrud Russell M.
Published: July 2002

The stellarator neoclassical transport caused by particles trapped in local helical wells is calculated in the low-collisionality regime using a systematic expansion. The behavior of electron transport is found to be the same over a wide range of energies but the behavior of ion transport for low-energy ions is found to be different than that for high-energy ions. Furthermore, the electron fluxes do not vary with the change in the radial ambipolar electric field nearly as much as do the ion fluxes. Thus the particle diffusion is controlled by the electrons. A nonradial ambipolar electric field is induced by ion drift. This electric field enhances the transport by about 15%–20%. A convenient graphical method that allows one to determine the magnitude of the radial ambipolar field for machines with different parameters is presented. Numerical examples show that electron energy confinement time is comparable to the ion energy confinement time for all the different size stellarators studied. Although the neoclassical losses are large, it is shown that ignition can be achieved in a reasonably sized stellarator reactor. Finally, fron the standpoint of reactor economics, the confinement scaling law shows that in order to increase nτ, it is better to increase the aspect ratio than the overall dimensions of the reactor.
The dynamics of three vortices revisited
Authors: Tavantzis John , Ting Lu
Published: July 2002

The dynamics of three vortices was studied by Synge using the length of the sides of the triangle formed by three vortices as prime variables. The critical states at which the lengths of the sides remain fixed throughout the motion were found to be either equilateral triangles or collinear configurations. The equilateral configurations were shown to be stable or unstable depending on whether the sum of the products of strengths K was greater or less than zero, respectively. In the case K=0, a one-parameter family of solutions of contracting and another of expanding similar triangles were found. In this paper, it is shown that for this special case, the family of contracting similar solutions is always unstable while the family of expanding ones is stable. The critical states for collinear configurations in the general case are then studied where K is greater than or less than 0. It is shown that there are either six or four critical states depending on the strengths of the vortices. When there are six collinear critical states, three of them are always stable, one is not while the remaining two are unstable (stable) if the equilateral triangle configuration is stable (unstable). When there are only four collinear critical states, they are all stable while the equilateral triangle configuration is always unstable. Since there are two equilateral triangle configurations, clockwise and counterclockwise arrangements of the three vortices, the sum of the indices of all the critical states is equal to +2 regardless of whether K is greater than or less than 0. An integral invariant in trilinear coordinates is derived. When all the critical points and the integral invariant are known, the global behavior of the trajectories is obtained.
Linear stability of lid-driven cavity flow
Authors: Ramanan Natarajan , Homsy George M.
Published: July 2002

Previous experimental studies indicate that the steady two-dimensional flow in a lid-driven cavity becomes unstable and goes through a sequence of transitions before becoming turbulent. In this study, an analysis of this instability is undertaken. The two-dimensional base flow is computed numerically over a range of Reynolds numbers and is perturbed with three-dimensional disturbances. The partial differential equations governing the evolution of these perturbations are then obtained using linear stability analysis and normal mode analysis. Using a finite difference discretization, a generalized eigenvalue problem is formulated from these equations whose solution gives the dispersion relation between complex growth rate and wave number. An eigenvalue solver using simultaneous iteration is employed to identify the dominant eigenvalue which is indicative of the growth rate of these perturbations and the associated eigenfunction which characterizes the secondary state. This paper presents stability curves to identify the critical Reynolds number and the critical wavelength of the neutral mode and discusses the mechanism of instability through energy calculations. This paper finds that the loss of stability of the base flow is due to a long wavelength mode at a critical Reynolds number (Re) of 594. The mechanism is analyzed through a novel application of the Reynolds–Orr equations and shown to be due to a Goertler type instability. The stability curves are relatively flat indicating that this state will be challenged by many shorter wavelength modes at a slightly higher Reynolds number. In fact, a second competing mode with a wavelength close to the cavity width was found to be unstable at Re=730. The present results of the reconstructed flow based on these eigenfunctions at the neutral state, show striking similarities to the experimental observations.
Numerical study of instability in a horizontal porous channel with bottom heating and forced horizontal flow
Authors: Dufour Françoise , Neel Marie-Christine
Published: July 2002

We study the two-dimensional convective patterns in a long horizontal porous layer heated from below, where a nonzero cross-flow is imposed. Indeed experiments show that time-periodic planar flows are found at moderate values of the flow rate. Within the framework of the Darcy law, above the absolute threshold, varied end-conditions lead to oscillatory patterns, which are more or less similar to each other in the bulk of the device but present differences near the extremities. Depending on the boundary-conditions, the numerical simulation may produce patterns which are space-periodic traveling rolls or waves of amplitude modulated within a stationary region, with envelopes in the form of fronts. Space-periodic boundary-conditions yield wavelengths linked to the total length of the device, which sets the frequency. Input boundary-conditions breaking translational invariance along the direction of the main flow yield different structures and select the temporal period. Most attention is paid to inlet-conditions imposing a linear profile of temperature (at the entrance of the device). We study the variations of the frequency vs the seeping flow rate and the filtration Rayleigh number. The length of the resulting front is also considered.
On how a joint interaction of two innocent partners (smooth advection and linear damping) produces a strong intermittency
Authors: Chertkov M.
Published: July 2002

Forced advection of passive scalar by a smooth d-dimensional incompressible velocity in the presence of linear damping is studied. Acting separately advection and damping do not lead to an essential intermittency of the steady scalar statistics, while being mixed together produce a very strong non-Gaussianity in the convective range: 2n-th moment of scalar difference, 〈[θ(t;r)−θ(t;0)]2n〉 is proportional to rξ2n, ξ2n=min{2n,d2/4+2αdn/[(d−1)D]−d/2}, where α/D measures the rate of the damping in the units of the stretching rate. The probability density function (PDF) of the scalar difference is also found.
On acoustic cavitation of slightly subcritical bubbles
Authors: Harkin Anthony , Nadim Ali , Kaper Tasso J.
Published: July 2002

The classical Blake threshold indicates the onset of quasistatic evolution leading to cavitation for gas bubbles in liquids. When the mean pressure in the liquid is reduced to a value below the vapor pressure, the Blake analysis identifies a critical radius which separates quasistatically stable bubbles from those which would cavitate. In this work, we analyze the cavitation threshold for radially symmetric bubbles whose radii are slightly less than the Blake critical radius, in the presence of time-periodic acoustic pressure fields. A distinguished limit equation is derived that predicts the threshold for cavitation for a wide range of liquid viscosities and forcing frequencies. This equation also yields frequency-amplitude response curves. Moreover, for fixed liquid viscosity, our study identifies the frequency that yields the minimal forcing amplitude sufficient to initiate cavitation. Numerical simulations of the full Rayleigh–Plesset equation confirm the accuracy of these predictions. Finally, the implications of these findings for acoustic pressure fields that consist of two frequencies will be discussed.
Self-sustained plasma turbulence due to current diffusion
Authors: Yagi M. , Itoh S.-I. , Itoh K. , Fukuyama A. , Azumi M.
Published: July 2002

Plasma turbulence and anomalous transport by the electrostatic current diffusive interchange mode are studied by the nonlinear simulation based on the magnetohydrodynamic model. The turbulence is found to have a typical characteristic of subcritical turbulence. The saturation level, as a function of the pressure gradient ∇p, is confirmed to scale like ‖∇p‖3/2. This nature holds independent of the ratio ‖∇p‖/‖∇pc‖ where ‖∇pc‖, is a critical pressure gradient against linear instability. The turbulence-driven transport is also evaluated. The simulation result confirms the theoretical prediction, which is based on the self-sustained turbulence, with respect to the nonlinear growth and damping. Both the normal cascade and inverse cascade are essential in establishing the stationary turbulent state.
Poloidal rotation in tokamaks with large electric field gradients
Authors: Hinton F. L. , Kim Y.-B.
Published: July 2002

The ion poloidal flow velocity near the plasma edge in a tokamak has been calculated by extending neoclassical theory to include orbit squeezing, which is the reduction of the ion banana widths due to radial electric field shear. The pressure gradient-driven ion parallel flow is reduced by orbit squeezing, and then no longer cancels the diamagnetic flow in its contribution to poloidal flow. This allows the poloidal flow velocity to be a significant fraction of the ion diamagnetic velocity, which can be much larger than the standard neoclassical value (proportional to the ion temperature gradient). Equations for determining the poloidal flow and radial electric field profiles self-consistently are given.
Positron trapping in a magnetic mirror configuration
Authors: Boehmer H. , Adams M. , Rynn N.
Published: July 2002

In a first step toward generating an electron–positron plasma, a proof-of-principle experiment is reported in which externally injected slow positrons are trapped in a magnetic mirror configuration by electron cyclotron resonance heating. With a primary flux of only 530 slow positrons/s from a 600 μCi Na-22 positron source/moderator system, an estimated equilibrium density of 5×102 cm−3 is obtained in a 20 cm3 volume. With an appropriate increase of the injected positron flux, densities in the 107 cm−3 range can be expected.
Bohm criterion for the collisional sheath
Authors: Valentini H.-B.
Published: July 2002

Using a two-fluid model it is shown analytically that in collisional slightly ionized plasmas, i.e., for many typical low pressure discharges, at the sheath edge the drift velocity of the plasma can be smaller than the ambipolar sound speed of the ions. This basic result was known earlier by numerical calculations but it is demonstrated here using simple analytical expressions. Under these conditions the Bohm criterion, in its usual formulation, is a sufficient condition for the existence of a positive boundary sheath, but it is not a necessary condition.
Scaling studies of the high mode pedestal
Authors: Groebner R. J. , Osborne T. H.
Published: July 2002

The structure and scaling of the H-mode (high mode) pedestal are examined for discharges in the DIII-D tokamak [Plasma Physics and Controlled Fusion Research (International Atomic Energy Agency, Vienna, 1986), p. 159]. For typical conditions, the pedestal values of the ion and electron temperatures Ti and Te are comparable. Measurements of main ion and C6+ profiles indicate that the ion pressure gradient in the barrier is 50%–100% of the electron pressure gradient for deuterium plasmas. The magnitude of the pressure gradient in the barrier often exceeds the predictions of infinite-n ballooning mode theory by a factor of 2. Moreover, via the bootstrap current, the finite pressure gradient acts to entirely remove ballooning stability limits for typical discharges. For a large dataset, the width of the pressure barrier δ is best described by the dimensionless scaling δ/R∝(βpolped)0.4 where (βpolped) is the pedestal value of poloidal beta and R is the major radius. Scalings based on the poloidal ion gyroradius or the edge density gradient do not adequately describe overall trends in the data set and the propagation of the pressure barrier observed between edge-localized modes. The width of the Ti barrier is quite variable and is not a good measure of the width of the pressure barrier.
Increased x-ray power generated from low-mass large-number aluminum-wire-array Z-pinch implosions
Authors: Sanford T. W. L. , Mock R. C. , Spielman R. B. , Peterson D. L. , Mosher D. , Roderick N. F.
Published: July 2002

A Saturn accelerator study of annular, aluminum-wire-array, Z-pinch implosions in the calculated high-wire-number plasma-shell regime [Phys. Rev. Lett. 77, 5063 (1996)] shows that a factor of 2 decrease in pulse width and an associated doubling of the total radiated x-ray power occurs when the mass of 12 mm radius, 2 cm long array is reduced from above 1.9 mg to below 1.3 mg. The study utilized extensive time- and space-resolved measurements to characterize the implosion over the mass range 0.42–3.4 mg. Eulerian radiation-magnetohydrodynamic-code simulations in the r-z plane agree qualitatively with the measurements. They suggest that the pulse-width decrease with mass is due to the faster implosion velocity of the plasma shell relative to the growth of the shell thickness that arises from a two-stage development of the magnetic Rayleigh–Taylor instability. Over the bulk of the mass-range explored, the variation in K-shell (lines plus free-bound continuum) yield is in qualitative agreement with simple K-shell radiation-scaling models. These models indicate that the doubling of the measured K-shell yield, which also occurs for masses below 1.3 mg relative to masses above 1.9 mg, arises from increased plasma temperature.
Polycrystalline thin-film Cu2−xSe/CdS solar cell
Authors: Chen Wen S. , Stewart J. M. , Mickelsen R. A.
Published: July 2002

The development of a polycrystalline thin-film solar cell utilizing a backwall designed heterojunction structure based upon p-type Cu2−xSe and n-type CdS semiconductor materials is described. The electrical, optical, and structural properties of the deposited thin-film materials are described. A device efficiency of 5.38% under simulated AM1 illumination is reported.
Laser chemical vapor deposition of gold
Authors: Baum Thomas H. , Jones Carol R.
Published: July 2002

High quality gold spots and lines have been deposited from gaseous dimethyl (2, 4-pentanedionato) gold (III) using a focused argon ion laser. Growth rates of 1 μm/s at power densities of 4×105 W/cm2 were obtained. Resistivity, threshold writing power densities, and deposition rates were measured and their relationship to the physical and chemical properties of the gaseous complex are explored.
Nonlinear photothermal imaging
Authors: Rajakarunanayake Y. N. , Wickramasinghe H. K.
Published: July 2002

A new technique is described whereby one can extract the nonlinear photothermal properties of a sample in photothermal microscopy. The basic scheme relies on chopping a pump heating beam at ω and detecting the temperature variation of the sample using a linear temperature sensor (in our case a mirage detector) tuned to 2ω. Harmonic images of cracks and other samples show very high contrast when compared with the fundamental image.
Pulsed CO2 laser etching of polyimide
Authors: Brannon J. H. , Lankard J. R.
Published: July 2002

Etching of thin polyimide films in air was investigated using a line tunable, pulsed CO2 laser. The threshold fluence for etching at a wavelength of 944 cm−1 (10.6 μm) exceeds that at 1087 cm−1 (9.2 μm) by a factor of 4. This is consistent with the infrared absorption spectrum which shows polyimide to be significantly more absorbing at 1087 cm−1. As a result, etching at 1087 cm−1 produces a cleaner, more precisely defined region. Analysis of the vapors generated during laser etching shows the simple gases CO2, H2O, and CO to be present.
Formation of polymer films by pulsed laser evaporation
Authors: Hansen S. G. , Robitaille T. E.
Published: July 2002

Films were produced by pulsed laser evaporation of various solid polymer targets in vacuum. Smooth films and relatively low deposition power thresholds (<107 W/cm2 peak) were observed for strongly absorbed ultraviolet wavelengths. Poorly absorbed wavelengths gave powdery deposits. For many polymers the evaporation process did not significantly alter the chemical structure, but the molecular weight was reduced.
Chemical durability of high-temperature superconductor YBa2Cu3O7−x in aqueous environments
Authors: Bansal Narottam P. , Sandkuhl Ann L.
Published: July 2002

The stability of YBa2Cu3O7−x in water and 100% humidity has been investigated at three temperatures using pH measurements, x-ray diffraction, and scanning electron microscopy. The oxide-ceramic superconductor is highly unstable and reacts rapidly with water and also degrades in moisture. Dissolution of the oxide perovskite in water is highly incongruent. The corrosion products are found to be BaCO3, CuO, O2, etc. Barium hydroxide is first formed which further reacts with atmospheric CO2 to form needle-shaped crystals of BaCO3. For any practical applications, devices made from these materials would have to be protected with an impermeable coating to prevent deterioration from atmosphere.
Femtosecond dynamics of rubredoxin: Tryptophan solvation and resonance energy transfer in the protein
Authors: Zhong Dongping , Pal Samir Kumar , Zhang Deqiang , Chan Sunney I. , Zewail Ahmed H.
Published: July 2002

We report here studies of tryptophan (Trp) solvation dynamics in
water and in the
Pyrococcus furiosus
rubredoxin protein,
including the native and its apo and denatured forms. We also report
results on energy transfer from Trp to the iron-sulfur [Fe-S]
cluster. Trp fluorescence decay with the onset of solvation dynamics of
the chromophore in water was observed with femtosecond resolution
(≈160 fs; 65% component), but the emission extended to the
picosecond range (1.1 ps; 35% component). In contrast, the decay is
much slower in the native rubredoxin; the Trp fluorescence decay
extends to 10 ps and longer, reflecting the local rigidity imposed by
residues and by the surface water layer. The dynamics of resonance
energy transfer from the two Trps to the [Fe-S] cluster in the
protein was observed to follow a temporal behavior characterized by a
single exponential (15–20 ps) decay. This unusual observation in a
protein indicates that the resonance transfer is to an acceptor of a
well-defined orientation and separation. From studies of the mutant
protein, we show that the two Trp residues have similar energy-transfer
rates. The critical distance for transfer (R
0
) was
determined, by using the known x-ray data, to be 19.5 Å for Trp-36 and
25.2 Å for Trp-3, respectively. The orientation factor
(κ
2
) was deduced to be 0.13 for Trp-36, clearly
indicating that molecular orientation of chromophores in the protein
cannot be isotropic with κ
2
value of 2/3. These studies
of solvation and energy-transfer dynamics, and of the rotational
anisotropy, of the wild-type protein, the (W3Y, I23V, L32I) mutant, and
the fmetPfRd variant at various pH values reveal a dynamically rigid
protein structure, which is probably related to the
hyperthermophilicity of the protein.
Global organization of the Wordnet lexicon
Authors: Sigman Mariano , Cecchi Guillermo A.
Published: July 2002

The lexicon consists of a set of word meanings and their semantic relationships. A systematic representation of the English lexicon based in psycholinguistic considerations has been put together in the database Wordnet in a long-term collaborative effort. We present here a quantitative study of the graph structure of Wordnet to understand the global organization of the lexicon. Semantic links follow power-law, scale-invariant behaviors typical of self-organizing networks. Polysemy (the ambiguity of an individual word) is one of the links in the semantic network, relating the different meanings of a common word. Polysemous links have a profound impact in the organization of the semantic graph, conforming it as asmall worldnetwork, with clusters of high traffic (hubs) representing abstract concepts such asline,head, orcircle. Our results show that: (i) Wordnet has global properties common to many self-organized systems, and (ii) polysemy organizes the semantic graph in a compact and categorical representation, in a way that may explain the ubiquity of polysemy across languages.
Flexibility and packing in proteins
Authors: Halle Bertil
Published: July 2002

Structural flexibility is an essential attribute, without which few proteins could carry out their biological functions. Much information about protein flexibility has come from x-ray crystallography, in the form of atomic mean-square displacements (AMSDs) or
B
factors. Profiles showing the AMSD variation along the polypeptide chain are usually interpreted in dynamical terms but are ultimately governed by the local features of a highly complex energy landscape. Here, we bypass this complexity by showing that the AMSD profile is essentially determined by spatial variations in local packing density. On the basis of elementary statistical mechanics and generic features of atomic distributions in proteins, we predict a direct inverse proportionality between the AMSD and the contact density, i.e., the number of noncovalent neighbor atoms within a local region of ∼1.5 nm
3
volume. Testing this local density model against a set of high-quality crystal structures of 38 nonhomologous proteins, we find that it accurately and consistently reproduces the prominent peaks in the AMSD profile and even captures minor features, such as the periodic AMSD variation within α helices. The predicted rigidifying effect of crystal contacts also agrees with experimental data. With regard to accuracy and computational efficiency, the model is clearly superior to its predecessors. The quantitative link between flexibility and packing density found here implies that AMSDs provide little independent information beyond that contained in the mean atomic coordinates.
Ryanodine receptor point mutant E4032A reveals an allosteric interaction with ryanodine
Authors: Fessenden James D. , Chen Lili , Wang Yaming , Paolini Cecilia , Franzini-Armstrong Clara , Allen Paul D. , Pessah Isaac N.
Published: July 2002

The ryanodine receptor (RyR) family of proteins constitutes a
unique type of calcium channel that mediates Ca
2+
release
from endoplasmic reticulum/sarcoplasmic reticulum stores. Ryanodine
has been widely used to identify contributions made by the RyR to
signaling in both muscle and nonmuscle cells. Ryanodine, through
binding to high- and low-affinity sites, has been suggested to block
the channel pore based on its ability to induce partial conductance
states and irreversible inhibition. We examined the effect of ryanodine
on an RyR type 1 (RyR1) point mutant (E4032A) that exhibits a severely
compromised phenotype. When expressed in 1B5 (RyR null/dyspedic)
myotubes, E4032A is relatively unresponsive to stimulation by cell
membrane depolarization or RyR agonists, although the full-length
protein is correctly targeted to junctions and interacts with
dihydropyridine receptors (DHPRs) inducing their arrangement into
tetrads. However, treatment of E4032A-expressing cells with 200–500
μM ryanodine, concentrations that rapidly activate and then inhibit
wild-type (wt) RyR1, restores the responsiveness of E4032A-expressing
myotubes to depolarization and RyR agonists. Moreover, the restored
E4032A channels remain resistant to subsequent exposure to ryanodine.
In single-channel studies, E4032A exhibits infrequent (channel-open
probability, P
o
< 0.005) and brief (<250 μs) gating
events and insensitivity to Ca
2+
. Addition of ryanodine
restores Ca
2+
-dependent channel activity exhibiting full,
3/4, 1/2, and 1/4 substates. This evidence suggests that, whereas
ryanodine does not occlude the RyR pore, it does bind to sites that
allosterically induce substantial conformational changes in the RyR. In
the case of E4032A, these changes overcome unfavorable energy barriers
introduced by the E4032A mutation to restore channel function.
Laser capture microdissection analysis of gene expression in macrophages from atherosclerotic lesions of apolipoprotein E-deficient mice
Authors: Trogan Eugene , Choudhury Robin P. , Dansky Hayes M. , Rong James X. , Breslow Jan L. , Fisher Edward A.
Published: July 2002

Macrophage foam cells are integral in the development of atherosclerotic lesions. Gene expression analysis of lesional macrophage foam cells is complicated by the cellular heterogeneity of atherosclerotic plaque and the presence of lesions of various degrees of severity. To overcome these limitations, we tested the ability of laser capture microdissection (LCM) and real-time quantitative reverse transcription PCR to selectively analyze RNA from lesional macrophages of apolipoprotein E (apoE)-deficient mice. Proximal aortic tissue sections were immunostained for macrophagespecific CD68/macrosialin by a rapid (≈15-min) protocol. Alternating sections from each animal were used to isolate RNA either from entire sections (analogous to isolation from whole tissue) or by LCM selection of CD68-positive cells. We measured the mRNA levels of CD68, a macrophage-specific marker, α-actin, a smooth muscle cell marker, and cyclophilin A, a control gene. Compared with whole sections, CD68 mRNA levels were greatly enriched (33.6-fold) in the laser-captured lesional macrophages. In contrast to whole sections, LCM-derived RNA had undetectable levels of α-actin. To illustrate the ability of this method to measure changes in lesional macrophage gene expression, we injected 100 μg of lipopolysaccharide i.p. into apoE-deficient mice and detected in laser-captured lesional macrophages increased mRNA expression for vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 (11.9-, 32.5-, and 31.0-fold, respectively). By selectively enriching foam cell RNA, LCM provides a powerful approach to study thein situexpression and regulation of atherosclerosis-related genes. This approach will allow the study of macrophage gene expression under various conditions of plaque formation, regression, and response to genetic and environmental perturbations.
Matching gene activity with physiological functions
Authors: Huang Wei , Sher Yuh-Pyng , Peck Konan , Fung Yuan Cheng B.
Published: July 2002

Matching the activity of the genes with biomechanics and physiology is an effective way to use cDNA microarray technology. Required are data on the change of activities of genes associated with specific physiological functions with respect to a continuous variable such as time. For each pair of data (gene and physiological function) as functions of time, we can compute a coefficient of correlation,
R
. The correlation is perfect if
R
is +1 or −1; it is nonexistent if
R
= 0. By evaluating
R
for every gene in a microarray, we can arrange the genes in the order of the number
R
, thus learning which genes are best correlated with the mechanical or physiological function. We illustrate this procedure by studying the blood vessels in the lung in response to pulmonary hypoxic hypertension, including the remodeling of vascular morphometry, the elastic moduli, and the zero-stress state of the vessel wall. For each physiological function, we identify the top genes that correlate the best. We found that different genes correlate best with a given function in large and small arteries, and that the genes in pulmonary veins which respond to arterial functions are different from those in pulmonary arteries. We found one set of genes matching the remodeling of arterial wall thickness, but another set of genes whose integral of activity over time best fit the wall thickness change. Our method can be used to study other thought-provoking problems.
Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis
Authors: Waheed Abdul , Grubb Jeffrey H. , Zhou Xiao Yan , Tomatsu Shunji , Fleming Robert E. , Costaldi Mark E. , Britton Robert S. , Bacon Bruce R. , Sly William S.
Published: July 2002

The protein defective in hereditary hemochromatosis, called HFE, is similar to MHC class I-type proteins and associates with β
2
-microglobulin (β
2
M). Its association with β
2
M was previously shown to be necessary for its stability, normal intracellular processing, and cell surface expression in transfected COS cells. Here we use stably transfected Chinese hamster ovary cell lines expressing both HFE and β
2
M or HFE alone to study the effects of β
2
M on the stability and maturation of the HFE protein and on the role of HFE in transferrin receptor 1 (TfR1)-mediated iron uptake. In agreement with prior studies on other cell lines, we found that overexpression of HFE, without overexpressing β
2
M, resulted in a decrease in TfR1dependent iron uptake and in lower iron levels in the cells, as evidenced by ferritin and TfR1 levels measured at steady state. However, overexpression of both HFE and β
2
M had the reverse effect and resulted in an increase in TfR1-dependent iron uptake and increased iron levels in the cells. The HFE-β
2
M complex did not affect the affinity of TfR1 for transferrin or the internalization rate of transferrin-bound TfR1. Instead, HFE-β
2
M enhanced the rate of recycling of TfR1 and resulted in an increase in the steady-state level of TfR1 at the cell surface of stably transfected cells. We propose that Chinese hamster ovary cells provide a model to explain the effect of the HFE-β
2
M complex in duodenal crypt cells, where the HFE-β
2
M complex appears to facilitate the uptake of transferrin-bound iron to sense the level of body iron stores. Impairment of this process in duodenal crypt cells leads them to be iron poor and to signal the differentiating enterocytes to take up iron excessively after they mature into villus cells in the duodenum of hereditary hemochromatosis patients.
Selecting protein targets for structural genomics of
Pyrobaculum aerophilum
: Validating automated fold assignment methods by using binary hypothesis testing
Authors: Mallick Parag , Goodwill Kenneth E. , Fitz-Gibbon Sorel , Miller Jeffrey H. , Eisenberg David
Published: July 2002

Three-dimensional protein folds were assigned to all ORFs of the
recently sequenced genome of the hyperthermophilic archaeon
Pyrobaculum aerophilum.
Binary hypothesis testing was
used to estimate a confidence level for each assignment. A separate
test was conducted to assign a probability for whether each sequence
has a novel fold—i.e., one that is not yet represented in the
experimental database of known structures. Of the 2,130 predicted
nontransmembrane proteins in this organism, 916 matched a fold at a
cumulative 90% confidence level, and 245 could be assigned at a 99%
confidence level. Likewise, 286 proteins were predicted to have a
previously unobserved fold with a 90% confidence level, and 14 at a
99% confidence level. These statistically based tools are combined
with homology searches against the Online Mendelian Inheritance in Man
(OMIM) human genetics database and other protein databases for the
selection of attractive targets for crystallographic or NMR structure
determination. Results of these studies have been collated and placed
at
http://www.doe-mbi.ucla.edu/people/parag/PA_HOME/
,
the University of California, Los Angeles–Department of Energy
Pyrobaculum aerophilum
web site.
Structure of a flavin-binding plant photoreceptor domain: Insights into light-mediated signal transduction
Authors: Crosson Sean , Moffat Keith
Published: July 2002

Phototropin, a major blue-light receptor for phototropism in seed
plants, exhibits blue-light-dependent autophosphorylation and contains
two light, oxygen, or voltage (LOV) domains and a serine/threonine
kinase domain. The LOV domains share homology with the PER-ARNT-SIM
(PAS) superfamily, a diverse group of sensor proteins. Each LOV domain
noncovalently binds a single FMN molecule and exhibits reversible
photochemistry
in vitro
when expressed separately or in
tandem. We have determined the crystal structure of the LOV2 domain
from the phototropin segment of the chimeric fern photoreceptor phy3 to
2.7-Å resolution. The structure constitutes an FMN-binding fold that
reveals how the flavin cofactor is embedded in the protein. The
single LOV2 cysteine residue is located 4.2 Å from flavin atom C(4a),
consistent with a model in which absorption of blue light induces
formation of a covalent cysteinyl-C(4a) adduct. Residues that interact
with FMN in the phototropin segment of the chimeric fern photoreceptor
(phy3) LOV2 are conserved in LOV domains from phototropin of other
plant species and from three proteins involved in the regulation of
circadian rhythms in
Arabidopsis
and
Neurospora
. This conservation suggests that these
domains exhibit the same overall fold and share a common mechanism
for flavin binding and light-induced signaling.
Crystal structure of the ectodomain of Methuselah, a
Drosophila
G protein-coupled receptor associated with extended lifespan
Authors: West Anthony P. , Llamas Lynda L. , Snow Peter M. , Benzer Seymour , Bjorkman Pamela J.
Published: July 2002

The
Drosophila
mutant
methuselah
(
mth
) was identified from a screen for single gene
mutations that extended average lifespan.
Mth
mutants
have a 35% increase in average lifespan and increased resistance to
several forms of stress, including heat, starvation, and oxidative
damage. The protein affected by this mutation is related to G
protein-coupled receptors of the secretin receptor family. Mth, like
secretin receptor family members, has a large N-terminal ectodomain,
which may constitute the ligand binding site. Here we report the 2.3-Å
resolution crystal structure of the Mth extracellular region, revealing
a folding topology in which three primarily β-structure-containing
domains meet to form a shallow interdomain groove containing a
solvent-exposed tryptophan that may represent a ligand binding site.
The Mth structure is analyzed in relation to predicted Mth homologs and
potential ligand binding features.
Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands
Authors: Riou J. F. , Guittat L. , Mailliet P. , Laoui A. , Renou E. , Petitgenet O. , Mégnin-Chanet F. , Hélène C. , Mergny J. L.
Published: July 2002

Telomeres of human chromosomes contain a G-rich 3′-overhang that adopts an intramolecular G-quadruplex structure
in vitro
which blocks the catalytic reaction of telomerase. Agents that stabilize G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalyzed by telomerase and can therefore act as antitumor agents. We have identified by Fluorescence Resonance Energy Transfer a new series of quinoline-based G-quadruplex ligands that also exhibit potent and specific anti-telomerase activity with IC
50
in the nanomolar concentration range. Long term treatment of tumor cells at subapoptotic dosage induces a delayed growth arrest that depends on the initial telomere length. This growth arrest is associated with telomere erosion and the appearance of the senescent cell phenotype (large size and expression of β-galactosidase activity). Our data show that a G-quadruplex interacting agent is able to impair telomerase function in a tumor cell thus providing a basis for the development of new anticancer agents.
Sexually dimorphic expression of estrogen receptor β in the anteroventral periventricular nucleus of the rat preoptic area: Implication in luteinizing hormone surge
Authors: Orikasa Chitose , Kondo Yasuhiko , Hayashi Shinji , McEwen Bruce S. , Sakuma Yasuo
Published: July 2002

Striking sex difference was detected in the expression of estrogen receptor (ER) β mRNA and protein by nonisotopic
in situ
hybridization and immunohistochemistry in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly larger number of ERβ mRNA-positive cells were visualized in the medial-most portion of the AVPV within 50 μm from the ependymal lining of the third ventricle. Rats of 7, 14, 21, 35, and 60 days of age (d 1 = day of birth) showed the sex difference. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on d 14. In the AVPV of adult females, ERα immunoreactivity colocalized in 83% of ERβ mRNA-positive cells. Tyrosine hydroxylase immunoreactivity colocalized in 18% of ERβ immunoreactive cells in d 21 females. Infusion of an ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERβ in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen.
Structural requirement of bilin chromophore for the photosensory specificity of phytochromes A and B
Authors: Hanzawa Hiroko , Shinomura Tomoko , Inomata Katsuhiko , Kakiuchi Takashi , Kinoshita Hideki , Wada Keishiro , Furuya Masaki
Published: July 2002

Phytochromes are an important class of chromoproteins that regulate many cellular and developmental responses to light in plants. The model plant species
Arabidopsis thaliana
possesses five phytochromes, which mediate distinct and overlapping responses to light. Photobiological analyses have established that, under continuous irradiation, phytochrome A is primarily responsible for plant's sensitivity to far-red light, whereas the other phytochromes respond mainly to red light. The present study reports that the far-red light sensitivity of phytochrome A depends on the structure of the linear tetrapyrrole (bilin) prosthetic group. By reconstitution of holophytochrome
in vivo
through feeding various synthetic bilins to chromophore-deficient mutants of
Arabidopsis
, the requirement for a double bond on the bilin D-ring for rescuing phytochrome A function has been established. In contrast, we show that phytochrome B function can be rescued with various bilin analogs with saturated D-ring substituents.
Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine
Authors: Beck Konrad , Chan Virginia C. , Shenoy Nigel , Kirkpatrick Alan , Ramshaw John A. M. , Brodsky Barbara
Published: July 2002

Mutations resulting in replacement of one obligate Gly residue within the repeating (Gly-Xaa-Yaa)
n
triplet pattern of the collagen type I triple helix are the major cause of osteogenesis imperfecta (OI). Phenotypes of OI involve fragile bones and range from mild to perinatal lethal. In this study, host–guest triple-helical peptides of the form acetyl-(Gly-Pro-Hyp)
3
-
Zaa
-Pro-Hyp-(Gly-Pro-Hyp)
4
-Gly-Gly-amide are used to isolate the influence of the residue replacing Gly on triple-helix stability, with Zaa = Gly, Ala, Arg, Asp, Glu, Cys, Ser, or Val. Any substitution for Zaa = Gly (melting temperature,
T
m
= 45°C) results in a dramatic destabilization of the triple helix. For Ala and Ser,
T
m
decreases to ≈10°C, and for the Arg-, Val-, Glu-, and Asp-containing peptides,
T
m
< 0°C. A Gly → Cys replacement results in
T
m
< 0°C under reducing conditions but shows a broad transition (
T
m
≈ 19°C) in an oxidizing environment. Addition of trimethylamine
N
-oxide increases
T
m
by ≈5°C per 1 M trimethylamine
N
-oxide, resulting in stable triple-helix formation for all peptides and allowing comparison of relative stabilities. The order of disruption of different Gly replacements in these peptides can be represented as Ala ≤ Ser < CPO
red
< Arg < Val < Glu ≤ Asp. The rank of destabilization of substitutions for Gly in these Gly-Pro-Hyp-rich homotrimeric peptides shows a significant correlation with the severity of natural OI mutations in the α1 chain of type I collagen.
On strategies for reducing greenhouse gas emissions
Authors: Bolin Bert , Kheshgi Haroon S.
Published: July 2002

Equity is of fundamental concern in the quest for international
cooperation to stabilize greenhouse gas concentrations by the reduction
of emissions. By modeling the carbon cycle, we estimate the global
CO
2
emissions that would be required to stabilize the
atmospheric concentration of CO
2
at levels ranging from 450
to 1,000 ppm. These are compared, on both an absolute and a per-capita
basis, to scenarios for emissions from the developed and developing
worlds generated by socio-economic models under the assumption that
actions to mitigate greenhouse gas emissions are not taken. Need and
equity have provided strong arguments for developing countries to
request that the developed world takes the lead in controlling its
emissions, while permitting the developing countries in the
meantime to use primarily fossil fuels for their development. Even with
major and early control of CO
2
emissions by the developed
world, limiting concentration to 450 ppm implies that the developing
world also would need to control its emissions within decades, given
that we expect developing world emissions would otherwise double over
this time. Scenarios leading to CO
2
concentrations of 550
ppm exhibit a reduction of the developed world's per-capita emission
by about 50% over the next 50 years. Even for the higher stabilization
levels considered, the developing world would not be able to use fossil
fuels for their development in the manner that the developed world has
used them.
De novo
design of biomimetic antimicrobial polymers
Authors: Tew Gregory N. , Liu Dahui , Chen Bin , Doerksen Robert J. , Kaplan Justin , Carroll Patrick J. , Klein Michael L. , DeGrado William F.
Published: July 2002

The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor with both fundamental and practical implications. Recently, a number of nonnatural peptides with designed sequences have been elaborated to provide biologically active structures; in particular, facially amphiphilic peptides built from β-amino acids have been shown to mimic both the structures as well as the biological function of natural antimicrobial peptides such as magainins and cecropins. However, these natural peptides as well as their β-peptide analogues are expensive to prepare and difficult to produce on a large scale, limiting their potential use to certain pharmaceutical applications. We therefore have designed a series of facially amphiphilic arylamide polymers that capture the physical and biological properties of this class of antimicrobial peptides, but are easy to prepare from inexpensive monomers. The design process was aided by molecular calculations with density functional theory-computed torsional potentials. This new class of amphiphilic polymers may be applied in situations where inexpensive antimicrobial agents are required.
Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity
Authors: Gisselsson David , Pettersson Louise , Höglund Mattias , Heidenblad Markus , Gorunova Ludmila , Wiegant Joop , Mertens Fredrik , Dal Cin Paola , Mitelman Felix , Mandahl Nils
Published: July 2002

It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence
in situ
hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system for clonal evolution and progression.
Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep
Authors: Pinzar Elena , Kanaoka Yoshihide , Inui Takashi , Eguchi Naomi , Urade Yoshihiro , Hayaishi Osamu
Published: July 2002

To examine the function of prostaglandin (PG) D synthase (PGDS) gene, as well as endogenously produced PGD
2
in sleep regulation
in vivo
, we generated transgenic (TG) mice that overexpress human PGDS gene to study their sleep behavior. Although no difference was observed in the sleep/wake patterns between wild-type and TG mice, a striking time-dependent increase in non-rapid eye movement (NREM), but not in rapid eye movement (REM), sleep was observed in two independent lines of TG mice after stimulation by tail clipping. Concomitantly, the spontaneous locomotor activity of TG animals was drastically decreased in response to the tail clip. Induction of NREM sleep in TG mice was positively correlated with the PGD
2
production in the brain. Sleep, locomotion, and PGD
2
content were essentially unchanged in wild-type mice after tail clipping. The results with TG mice demonstrate the involvement of the PGDS gene in the regulation of NREM sleep.