bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of oxygen diffusion during hydrogen passivation of shallow-acceptor impurities in single-crystal silicon
Authors: Johnson N. M. , Moyer M. D.
Published: July 2002

It was recently proposed that hydrogen compensation of shallow-acceptor impurities in single-crystal silicon is due to the diffusion of both monatomic oxygen and hydrogen into silicon which combine at acceptor sites to form neutral acceptor-OH complexes. It is shown here that oxygen does not diffuse into silicon under the conditions of shallow-acceptor passivation. Boron-doped silicon was exposed to monatomic deuterium and mass 18 oxygen at elevated temperatures. Depth profiles of D and 18O were measured by secondary-ion mass spectrometry for comparison with the boron concentration. While D readily diffuses into silicon with the concentration nearly equal to that of the boron, no 18O was detectable above the background level. Deuterium profiles in both phosphorus-doped and boron-doped silicon further reveal high densities of deuterium, in excess of the boron concentration, which are ascribed to diffusing monatomic deuterium and deuterium that is immobilized through recombination and impurity trapping.
GaAs/GaAs1−ySby strained-layer superlattices grown by molecular beam epitaxy
Authors: Klem J. , Peng C. K. , Henderson T. , Morkoç H. , Otsuka N. , Choi C. , Yu P. W.
Published: July 2002

GaAs/GaAs1−ySby superlattices have been grown by molecular beam epitaxy and characterized by x-ray diffraction, transmission electron microscopy, and low-temperature photoluminescence. Transmission electron microscopy and x-ray results indicate that high quality superlattices may be grown for lattice mismatches up to 3.1%. These structures exhibit luminescence at wavelengths as long as 1.7 μm, making them candidates for infrared device applications.
Measurement of high boron concentrations in silicon by infrared spectroscopy
Authors: Sopori B. L.
Published: July 2002

A new absorption line corresponding to an electronic transition P3/2→P1/2 at 668 cm−1 is used to measure high concentrations of boron in silicon. The calibration constant at 12 K is determined from the measurements on single-crystal silicon. A linear relationship between the absorbance and boron concentration is established up to 1017 cm−3 doping levels. Application of this measurement technique to large grain polycrystalline silicon is discussed.
Anode-temperature dependence of ion beam turn-on time in magnetically insulated pulsed ion diodes
Authors: Yoneda H. , Horioka K. , Ohbayashi K. , Kasuya K.
Published: July 2002

The temperature effect of anode dielectric materials on ion beam turn-on time is examined in a magnetically insulated pulsed ion diode. It is observed that the turn-on time decreased with temperature increase. This effect may be explained by a simple model in which electrons bombard the anode surface to generate desorbed and evaporated gas and trigger surface flashover to produce an anode plasma.
Epitaxial growth of rare-earth silicides on (111) Si
Authors: Knapp J. A. , Picraux S. T.
Published: July 2002

Rapid heating with an electron beam has been used to react overlayers of rare-earth (RE) metals with (111) Si, forming epitaxial layers of silicides of Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu. Under conventional furnace annealing, forming such silicides on Si typically leads to rough, pitted surfaces. The use of fast beam heating not only results in a much smoother surface topology but also helps promote epitaxial growth on (111) Si in both solid and liquid phase reactions. These epitaxial silicides have a hexagonal RESi∼1.7 structure (defected AlB2 type). Their orientation with the Si substrate is (0001)∥(111), with predicted lattice mismatches ranging from +0.83 to −2.55%.
Generation of highly monochromatic positrons using cold moderators
Authors: Brown B. L. , Crane W. S. , Mills A. P.
Published: July 2002

Slow positron beams generally employ a radioactive  β+ emitter with a crystal moderator in which the positrons thermalize. A small fraction of the thermalized positrons are desorbed at low (1–3 eV) energy, characteristic of the positron work function in the crystal. The energy width of the emitted positrons from W(110) and Ni(111) moderators can be narrowed significantly by cooling to liquid N2 temperatures. A practical configuration for a cooled moderator positron gun is presented which produces a narrow energy positron beam with good efficiency.
SiO2 buried layer formation by subcritical dose oxygen ion implantation
Authors: Stoemenos J. , Margail J. , Jaussaud C. , Dupuy M. , Bruel M.
Published: July 2002

The structure of the silicon dioxide buried layer formed by oxygen ion implantation at a subcritical dose i.e., 1.3×1018 ion cm−2 at 200 keV is studied. The beneficial effect of a high annealing temperature at 1300 °C for 6 h is discussed. A method for estimation of the total amount of SiO2 precipitated in the silicon overlayer is also presented, and these results are correlated with published electrical measurements.
Experimental determination of fuel density-radius product of inertial confinement fusion targets using secondary nuclear fusion reactions
Authors: Azechi H. , Miyanaga N. , Stapf R. O. , Itoga K. , Nakaishi H. , Yamanaka M. , Shiraga H. , Tsuji R. , Ido S. , Nishihara K. , Izawa Y. , Yamanaka T. , Yamanaka C.
Published: July 2002

The first demonstration of a fuel density-radius product measurement using secondary nuclear fusion reactions is presented. This technique involves using neutrons and protons generated by DT {T(d,n)α} and D3He {3He(d,p)α} fusion reactions, respectively, in a pure deuterium fuel.
Time-resolved studies of intense, relativistic electron beams with a subnanosecond Čerenkov electro-optic shutter
Authors: Hartemann F. , Bekefi G.
Published: July 2002

Time-resolved studies of intense, relativistic electron beams using a novel subnanosecond Čerenkov electro-optic shutter are described. The technique is applied to the measurements of the electron beam emittance from a multielectrode field emission gun (1.6 MV, 1 kA, 30 ns), and to the study of the stability of a rotating relativistic electron ring (200 kV, 100 A, 1 μs).
Monte Carlo algorithm for hot phonons in polar semiconductors
Authors: Lugli P. , Jacoboni C. , Reggiani L. , Kocevar P.
Published: July 2002

We present a novel ensemble Monte Carlo procedure for the study of electron and phonon dynamics during the relaxation of photoexcited hot carriers. For the first time hot-electron and hot-phonon effects are included together in the same Monte Carlo simulation. The algorithm is applied to a simplified model of GaAs, consisting of one-type carriers (electrons) in a two-valley system (L and Γ valleys). The buildup of the phonon population on a picosecond scale is monitored, in parallel with the cooling of the electron distribution. As expected, the presence of nonequilibrium phonons is found to slow down the electron relaxation.
Growth of diamond thin films by dc plasma chemical vapor deposition
Authors: Suzuki Kazuhiro , Sawabe Atsuhito , Yasuda Hiroaki , Inuzuka Tadao
Published: July 2002

Diamond thin films have been formed by dc plasma chemical vapor deposition with a high growth rate (∼20 μm/h). The diamond has been grown from methane (CH4) and hydrogen (H2) mixed gases on Si and α-Al2O3 substrates at a pressure of 200 Torr without surface scratching by diamond or c-BN powder. The obtained films have good crystallinity in the sense of electron and x-ray diffraction. Vicker’s hardness of the film is the same as that of natural diamond (∼10 000 kg/mm2). The influence of the dc discharge in a low vacuum (∼200 Torr) on diamond synthesis will be discussed briefly.
Self-starting passive phase conjugate mirror with Ce-doped strontium barium niobate
Authors: Rakuljic George A. , Sayano Koichi , Yariv Amnon , Neurgaonkar Ratnakar R.
Published: July 2002

We report the use of Ce-doped SrxBa1−xNb2O6, x=0.60 and 0.75, as the holographic four-wave mixing medium in the construction of a self-starting passive phase conjugate mirror using internal reflection. Without correcting for Fresnel reflections, a steady-state phase conjugate reflectivity of 25% was measured with Sr0.75Ba0.25Nb2O6:Ce. The distortion correcting property of such a mirror was demonstrated using an imaging experiment.
Unexpected unidirectional anisotropy in amorphous Tb-Fe/Ni-Fe-Mo bilayer films
Authors: Hellman F. , van Dover R. B. , Gyorgy E. M.
Published: July 2002

The exchange interaction between amorphous Tb-Fe (a-Tb-Fe) and crystalline Ni-Fe-Mo produces a unidirectional anisotropy in the magnetically soft Ni-Fe-Mo layer. This anisotropy appeared anomalous because the magnetizations of the layers were previously believed to be orthogonal to each other. The magnitude of the unidirectional anisotropy is quite large by comparison to values quoted in the literature for Permalloy of a comparable thickness exchange coupled to an in-plane antiferromagnet. Precise measurement of the direction of the easy axis in a-Tb-Fe shows that it is in fact tilted at a small angle with respect to the normal to the Ni-Fe-Mo moment which lies in the film plane. An expression relating the unidirectional anisotropy to measured properties of the a-Tb-Fe layer fits the experimental results. The tilt appears to be the consequence of a nonperpendicular incident angle of deposition and depends critically on deposition parameters such as substrate temperature, Tb-Fe layer thickness and composition, and the incident angles of the Tb and Fe vapor beams.
Defect annihilation in shallow p+ junctions using titanium silicide
Authors: Wen D. S. , Smith P. L. , Osburn C. M. , Rozgonyi G. A.
Published: July 2002

The residual extended defects due to end-of-range ion implantation damage can be totally eliminated by Ti silicidation. Shallow p+ junctions were formed by amorphizing the silicon with Ge implantation (85 keV, 1×1015 cm−2) prior to implanting boron (85 keV, 1×1015 cm−2), recrystallizing the amorphous region at 550 °C, and then rapid thermal annealing at 1050 °C for 10 s. A buried sheet of interstitial dislocation loops lying below the surface remained. However, following a self-aligned Ti silicide process, the end-of-range defects due to Ge ion implantation damage were no longer observed in cross-sectional transmission electron micrographs. The annihilation of these end-of-range interstitial dislocation loops is attributed to the injection of vacancies during Ti silicidation.
Effect of inelastic scattering on resonant and sequential tunneling in double barrier heterostructures
Authors: Jonson M. , Grincwajg Anna
Published: July 2002

We demonstrate that the current through a double barrier heterostructure is independent of whether the electron tunneling mechanism is sequential or Fabry–Perot like. For typical experimental parameters we show that inelastic scattering, which destroys the phase coherence, is an important effect that strongly reduces the probability for coherent tunneling. As a result, the tunneling will be mainly incoherent (sequential). However, in a model calculation where the degree of coherency can be varied, we find that the tunneling current does not depend on which of the two mechanisms dominate as long as the resonant energy is well defined.
Germanium blocked-impurity-band far-infrared detectors
Authors: Watson Dan M. , Huffman James E.
Published: July 2002

Ge:Ga blocked-impurity-band detectors having long-wavelength thresholds of 190 μm and peak quantum efficiencies of 4% have been fabricated. This performance approaches that of state-of-the-art discrete Ge:Ga photoconductors, with the additional benefit of good response at wavelengths longer than that obtained with unstressed photoconductors.
cw laser action of Er3+ in double sensitized fluoroaluminate glass at room temperature
Authors: Heumann E. , Ledig M. , Ehrt D. , Seeber W. , Duczynski E. W. , Heide H.-J. v.d. , Huber G.
Published: July 2002

cw lasing at 1.6 μm was obtained for the first time in Cr, Yb, Er:fluoroaluminate glass. Double step pumping via Cr3+ and Yb3+ with a krypton laser yields a threshold pump power of 80 mW. Efficient lasing can be expected using glass samples of optimized dopant concentration and improved optical quality.
Study of electromigration-induced resistance and resistance decay in Al thin-film conductors
Authors: Lloyd J. R. , Koch R. H.
Published: July 2002

Using an ac Bridge technique, the resistance of thin-film (500 nm thick) Al and AlCu(5%) conductor stripes was monitored during high direct current density (1×106 A cm−2) stressing. The resistance was found to increase approximately linearly with time during stressing with a rate that was thermally activated. Surprisingly the activation energy varied considerably between nominally identical samples. After 3 h of stressing, the current was turned off and an exponential decay in the resistance was observed with a time constant of several hours. The decay was also thermally activated with an energy that varied from film to film. Both results suggest that the activation energy for resistance change during electrical stress can be significantly different in nominally identical films.
Indium diffusion in the chemical potential gradient at an In0.53Ga0.47As/In0.52Al0.48As interface
Authors: Baird R. J. , Potter T. J. , Kothiyal G. P. , Bhattacharya P. K.
Published: July 2002

We have measured the distribution of group III metals at In0.53Ga0.47As/In0.52Al0.48As interfaces before and after annealing at 1085 K. We find little evidence for Al interdiffusion, but the Ga concentration profiles show some broadening on annealing. Also, the originally nearly constant In profiles develop strong modulations with near discontinuities at the original interfaces. This phenomenon is explained and modeled in terms of In diffusion in the chemical potential gradient established by the disparity of the Al and Ga mobilities and the requirement of III-V stoichiometry in the alloys.
Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst
Authors: Parsons Lawrence M. , Denton Derek , Egan Gary , McKinley Michael , Shade Robert , Lancaster Jack , Fox Peter T.
Published: July 2002

Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is “vigilant” and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst.
Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase p85α
Authors: Almind Katrine , Delahaye Laurent , Hansen Torben , Van Obberghen Emmanuel , Pedersen Oluf , Kahn C. Ronald
Published: July 2002

Phosphatidylinositol 3-kinase is a key step in the metabolic actions of insulin. Two amino acid substitutions have been identified in the gene for the regulatory subunit of human p85α, Met-326Ile, and Asn-330Asp, and the former has been associated with alterations in glucose/insulin homeostasis. When the four human p85α proteins were expressed in yeast, a 27% decrease occurred in the level of protein expression of p85α
Ile/Asp
(
P
= 0.03) and a 43% decrease in p85α
Ile/Asn
(
P
= 0.08) as compared with p85α
Met/Asp
. Both p85α
Ile/Asp
and p85α
Ile/Asn
also exhibited increased binding to phospho-insulin receptor substrate-1 by 41% and 83%, respectively (
P
< 0.001), as compared with p85α
Met/Asp
. The expression of p85α
Ile
was also slightly decreased and the binding to insulin receptor substrate-1 slightly increased in brown preadipocytes derived from p85α knockout mice. Both p85α
Met
and p85α
Ile
had similar effects on AKT activity and were able to reconstitute differentiation of the preadipocytes, although the triglyceride concentration in fully differentiated adipocytes and insulin-stimulated 2-deoxyglucose uptake were slightly lower than in adipocytes expressing p85α
Met
. Thus, the Met-326Ile variant of p85α is functional for intracellular signaling and adipocyte differentiation but has small alterations in protein expression and activity that could play a role in modifying insulin action.
A feedback-controlled ensemble model of the stress-responsive hypothalamo-pituitary-adrenal axis
Authors: Keenan Daniel M. , Licinio Julio , Veldhuis Johannes D.
Published: July 2002

The present work develops and implements a biomathematical
statement of how reciprocal connectivity drives stress-adaptive
homeostasis in the corticotropic (hypothalamo-pituitary-adrenal) axis.
In initial analyses with this interactive construct, we test six
specific
a priori
hypotheses of mechanisms linking
circadian (24-h) rhythmicity to pulsatile secretory output. This
formulation offers a dynamic framework for later statistical estimation
of unobserved
in vivo
neurohormone secretion and
within-axis, dose-responsive interfaces in health and disease.
Explication of the core dynamics of the stress-responsive corticotropic
axis based on secure physiological precepts should help to unveil new
biomedical hypotheses of stressor-specific system failure.
Expression of the
Anabaena hetR
gene from a copper-regulated promoter leads to heterocyst differentiation under repressing conditions
Authors: Buikema William J. , Haselkorn Robert
Published: July 2002

Heterocyst differentiation in the filamentous cyanobacterium
Anabaena
PCC 7120 requires a functional
hetR
gene. Increased expression of the
hetR
gene is seen in developing and mature heterocysts
in response to fixed nitrogen limitation. We mapped four likely
transcriptional start sites for
hetR
and identified a
specific transcript that is positively autoregulated. By using the
copper-responsive
petE
promoter from
Anabaena
PCC 7120 to drive
hetR
expression, we show that ectopic expression of
hetR
increases heterocyst frequency and induces heterocyst differentiation
under fully repressing conditions. Coexpression of a reporter gene
shows that expression from the
petE
promoter is smoothly
induced depending on the amount of copper supplied. In the heterocyst
pattern mutant PatA, where terminally positioned heterocysts are formed
almost exclusively, expression of the
petE
∷
hetR
fusion does not result in
the formation of intercalary heterocysts. These results suggest that
although the intracellular concentration of HetR has to be elevated for
the differentiation decision, PatA plays a role as well. This role may
be in the form of posttranslational modification of HetR, because PatA
is a member of the response regulator family of proteins.
Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix
Authors: Allain Fabrice , Vanpouille Christophe , Carpentier Mathieu , Slomianny Marie-Christine , Durieux Sandrine , Spik Geneviève
Published: July 2002

Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPBKKK−, a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of α4β1 and α4β7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB–GAG interaction in the chemokine-like activity of this protein.
Metabolic efficiency and amino acid composition in the proteomes of
Escherichia coli
and
Bacillus subtilis
Authors: Akashi Hiroshi , Gojobori Takashi
Published: July 2002

Biosynthesis of an
Escherichia coli
cell, with organic compounds as sources of energy and carbon, requires approximately 20 to 60 billion high-energy phosphate bonds [Stouthamer, A. H. (1973)
Antonie van Leeuwenhoek
39, 545–565]. A substantial fraction of this energy budget is devoted to biosynthesis of amino acids, the building blocks of proteins. The fueling reactions of central metabolism provide precursor metabolites for synthesis of the 20 amino acids incorporated into proteins. Thus, synthesis of an amino acid entails a dual cost: energy is lost by diverting chemical intermediates from fueling reactions and additional energy is required to convert precursor metabolites to amino acids. Among amino acids, costs of synthesis vary from 12 to 74 high-energy phosphate bonds per molecule. The energetic advantage to encoding a less costly amino acid in a highly expressed gene can be greater than 0.025% of the total energy budget. Here, we provide evidence that amino acid composition in the proteomes of
E. coli
and
Bacillus subtilis
reflects the action of natural selection to enhance metabolic efficiency. We employ synonymous codon usage bias as a measure of translation rates and show increases in the abundance of less energetically costly amino acids in highly expressed proteins.
Inclusion of methylviologen in cucurbit[7]uril
Authors: Kim Hee-Joon , Jeon Woo Sung , Ko Young Ho , Kim Kimoon
Published: July 2002

The inclusion behavior of methylviologen (
N
,
N
′-dimethyl-4,4′-bipyridinium, MV) dication in cucurbit[7]uril (CB[7]) has been studied by using various spectroscopic and electrochemical methods. The inclusion complex of MV dication in CB[7] is stable thermodynamically and kinetically. The electrochemical study reveals that unlike β-cyclodextrin, CB[7] prefers the charged species, MV dication (MV
2+
), and cation radical (MV
+
⋅
) to the fully reduced neutral (MV
0
species as guests. Dimerization of MV
+
⋅
is suppressed effectively by forming a stable complex with CB[7] in aqueous solution as confirmed by spectroelectrochemical experiments. Furthermore, the first redox process (MV
2+
/MV
+
⋅
) of the MV
2+
–CB[7] complex occurs predominantly via the direct electron transfer pathway, whereas the second redox process (MV
+
⋅
/MV
0
) occurs via both the direct and indirect pathway because of the low affinity of the fully reduced species MV
0
to CB[7].
Cardiac fibrosis in mice lacking brain natriuretic peptide
Authors: Tamura Naohisa , Ogawa Yoshihiro , Chusho Hideki , Nakamura Kenji , Nakao Kazuki , Suda Michio , Kasahara Masato , Hashimoto Ryuju , Katsuura Goro , Mukoyama Masashi , Itoh Hiroshi , Saito Yoshihiko , Tanaka Issei , Otani Hiroki , Katsuki Motoya , Nakao Kazuwa
Published: July 2002

Cardiac fibrosis, defined as a proliferation of interstitial fibroblasts and biosynthesis of extracellular matrix components in the ventricles of the heart, is a consequence of remodeling processes initiated by pathologic events associated with a variety of cardiovascular disorders, which leads to abnormal myocardial stiffness and, ultimately, ventricular dysfunction. Brain natriuretic peptide (BNP) is a cardiac hormone produced primarily by ventricular myocytes, and its plasma concentrations are markedly elevated in patients with congestive heart failure and acute myocardial infarction. However, its precise functional significance has been undefined. In this paper, we report the generation of mice with targeted disruption of BNP (
Nppb
−/−
mice). We observed multifocal fibrotic lesions in the ventricles from
Nppb
−/−
mice. No signs of systemic hypertension and ventricular hypertrophy are noted in
Nppb
−/−
mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in
Nppb
−/−
mice, whereas no focal fibrotic changes are found in wild-type littermates (
Nppb
+/+
mice). This study establishes BNP as a cardiomyocyte-derived antifibrotic factor
in vivo
and provides evidence for its role as a local regulator of ventricular remodeling.
Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles
Authors: Vauthey Sylvain , Santoso Steve , Gong Haiyan , Watson Nicki , Zhang Shuguang
Published: July 2002

Several surfactant-like peptides undergo self-assembly to form nanotubes and nanovesicles having an average diameter of 30–50 nm with a helical twist. The peptide monomer contains 7–8 residues and has a hydrophilic head composed of aspartic acid and a tail of hydrophobic amino acids such as alanine, valine, or leucine. The length of each peptide is ≈2 nm, similar to that of biological phospholipids. Dynamic light-scattering studies showed structures with very discrete sizes. The distribution becomes broader over time, indicating a very dynamic process of assembly and disassembly. Visualization with transmission electron microscopy of quick-freeze/deep-etch sample preparation revealed a network of open-ended nanotubes and some vesicles, with the latter being able to “fuse” and “bud” out of the former. The structures showed some tail sequence preference. Many three-way junctions that may act as links between the nanotubes have been observed also. Studies of peptide surfactant molecules have significant implications in the design of nonlipid biological surfactants and the understanding of the complexity and dynamics of the self-assembly processes.
Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet
Authors: Lyons J. , Rauh-Pfeiffer A. , Yu Y. M. , Lu X.-M. , Zurakowski D. , Tompkins R. G. , Ajami A. M. , Young V. R. , Castillo L.
Published: July 2002

The availability of cysteine is thought to be the rate limiting factor for synthesis of the tripeptide glutathione (GSH), based on studies in rodents. GSH status is compromised in various disease states and by certain medications leading to increased morbidity and poor survival. To determine the possible importance of dietary cyst(e)ine availability for whole blood glutathione synthesis in humans, we developed a convenient mass spectrometric method for measurement of the isotopic enrichment of intact GSH and then applied it in a controlled metabolic study. Seven healthy male subjects received during two separate 10-day periods an
l
-amino acid based diet supplying an adequate amino acid intake or a sulfur amino acid (SAA) (methionine and cysteine) free mixture (SAA-free). On day 10,
l
-[1-
13
C]cysteine was given as a primed, constant i.v. infusion (3μmol⋅kg
−1
⋅h
−1
) for 6 h, and incorporation of label into whole blood GSH determined by GC/MS selected ion monitoring. The fractional synthesis rate (mean ± SD; day
-1
) of whole blood GSH was 0.65 ± 0.13 for the adequate diet and 0.49 ± 0.13 for the SAA-free diet (
P
< 0.01). Whole blood GSH was 1,142 ± 243 and 1,216 ± 162 μM for the adequate and SAA-free periods (
P
> 0.05), and the absolute rate of GSH synthesis was 747 ± 216 and 579 ± 135 μmol⋅liter
−1
⋅day
−1
, respectively (
P
< 0.05). Thus, a restricted dietary supply of SAA slows the rate of whole blood GSH synthesis and diminishes turnover, with maintenance of the GSH concentration in healthy subjects.
Conversion of a
c
type cytochrome to a
b
type that spontaneously forms
in vitro
from apo protein and heme: Implications for
c
type cytochrome biogenesis and folding
Authors: Tomlinson Esther J. , Ferguson Stuart J.
Published: July 2002

Cytochrome
c
552
from
Hydrogenobacter thermophilus
, a thermophilic bacterium, has been converted into a
b
type cytochrome, after mutagenesis of both heme-binding cysteines to alanine and expression in the cytoplasm of
Escherichia coli
. The
b
type variant is less stable, with the guanidine hydrochloride unfolding midpoint occurring at a concentration 2 M lower than for the wild-type protein. The reduction potential is 75 mV lower than that of the recombinant wild-type protein. The heme can be removed from the
b
type variant, thus generating an apo protein that has, according to circular dichroism spectroscopy, an α-helical content different from that of the holo
b
type protein. The latter is readily reformed
in vitro
by addition of heme to the apo protein. This reforming suggests that previously observed assembly of cytochrome
c
552
, which has the typical class I cytochrome
c
fold, in the
E. coli
cytoplasm is a consequence of spontaneous thioether bond formation after binding of heme to a prefolded polypeptide. These observations have implications for the general problem of
c
type cytochrome biogenesis.
Preferential binding of ATR protein to UV-damaged DNA
Authors: Ünsal-Kaçmaz Keziban , Makhov Alexander M. , Griffith Jack D. , Sancar Aziz
Published: July 2002

The ATR protein is a member of the phosphoinositide 3-kinase-related kinase family and plays an important role in UV-induced DNA damage checkpoint response. Its role as a signal transducer in cell cycle checkpoint is well established, but it is currently unclear whether ATR functions as a damage sensor as well. Here we have purified the ATR protein and investigated its interaction with DNA by using biochemical analysis and electron microscopy. We find that ATR is a DNA-binding protein with higher affinity to UV-damaged than undamaged DNA. In addition, damaged DNA stimulates the kinase activity of ATR to a significantly higher level than undamaged DNA. Our data suggest that ATR may function as an initial sensor in the DNA damage checkpoint response.
A core–BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes
Authors: Hakimi Mohamed-Ali , Bochar Daniel A. , Chenoweth Josh , Lane William S. , Mandel Gail , Shiekhattar Ramin
Published: July 2002

BRAF35, a structural DNA-binding protein, initially was identified as a component of a large BRCA2-containing complex. Biochemical analysis revealed the presence of a smaller core–BRAF35 complex devoid of BRCA2. Here we report the isolation of a six-subunit core–BRAF35 complex with the capacity to deacetylate histones, termed the BRAF–histone deacetylase complex (BHC), from human cells. BHC contains polypeptides reminiscent of the chromatin-remodeling complexes SWI/SNF and NuRD (nucleosome remodeling and deacetylating). Similar to NuRD, BHC contains an Mi2-like subunit, BHC80, and a PHD zinc-finger subunit as well as histone deacetylases 1/2 and an MTA-like subunit, the transcriptional corepressor CoREST. We show that BHC mediates repression of neuron-specific genes through the cis-regulatory element known as the repressor element 1 or neural restrictive silencer (RE1/NRS). Chromatin-immunoprecipitation experiments demonstrate the recruitment of BHC by the neuronal repressor REST. Expression of BRAF35 containing a single point mutation in the HMG domain of the protein abrogated REST-mediated transcriptional repression. These results demonstrate a role for core–BRAF35-containing complex in the regulation of neuron-specific genes through modulation of the chromatin structure.
Regulatory interaction of phosducin-like protein with the cytosolic chaperonin complex
Authors: McLaughlin Joseph N. , Thulin Craig D. , Hart Sarah J. , Resing Katheryn A. , Ahn Natalie G. , Willardson Barry M.
Published: July 2002

Phosducin and phosducin-like protein (PhLP) bind G protein βγ subunits and regulate their activity. This report describes a previously uncharacterized binding partner unique to PhLP that was discovered by coimmunoprecipitation coupled with mass spectrometric identification. Chaperonin containing tailless complex polypeptide 1 (CCT), a cytosolic chaperone responsible for the folding of many cellular proteins, binds PhLP with a stoichiometry of one PhLP per CCT complex. Unlike protein-folding substrates of CCT, which interact only in their nonnative conformations, PhLP binds in its native state. Native PhLP competes directly for binding of protein substrates of CCT and thereby inhibits CCT activity. Overexpression of PhLP inhibited the ability of CCT to fold newly synthesized β-actin by 80%. These results suggest that the interaction between PhLP and CCT may be a means to regulate CCT-dependent protein folding or alternatively, to control the availability of PhLP to modulate G protein signaling.
Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: Toward realistic long-term neurological gene therapy for chronic diseases
Authors: Thomas Clare E. , Schiedner Gudrun , Kochanek Stefan , Castro Maria G. , Löwenstein Pedro R.
Published: July 2002

Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, expression is eliminated by a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after peripheral infection with adenovirus. Here, we demonstrate that high-capacity adenoviral (HC-Ad) vectors succeed in maintaining long-term transgene expression in the brain, even in the presence of an active peripheral immunization with adenovirus that completely eliminates expression from first-generation vectors within 60 days. Importantly, even 60 days after the peripheral infection, brains injected with first-generation vectors exhibited evidence of a chronic infiltration of CD8
+
cells, macrophage/microglial activation, and up-regulation of brain MHC-I expression. No inflammation was observed in the brains injected with the HC-Ad vector. Thus, these results demonstrate that HC-Ad vectors will allow safe, stable, and long-term transgene expression in the brain, even in the presence of peripheral infection with adenovirus. This markedly improves the prospects for the use of adenoviral vectors for long-term gene therapy of neurological disorders.
Antillatoxin is a marine cyanobacterial toxin that potently activates voltage-gated sodium channels
Authors: Li W. I. , Berman F. W. , Okino T. , Yokokawa F. , Shioiri T. , Gerwick W. H. , Murray T. F.
Published: July 2002

Antillatoxin (ATX) is a lipopeptide derived from the pantropical marine cyanobacterium
Lyngbya majuscula
. ATX is neurotoxic in primary cultures of rat cerebellar granule cells, and this neuronal death is prevented by either
N-
methyl-
d
-aspartate (NMDA) receptor antagonists or tetrodotoxin. To further explore the potential interaction of ATX with voltage-gated sodium channels, we assessed the influence of tetrodotoxin on ATX-induced Ca
2+
influx in cerebellar granule cells. The rapid increase in intracellular Ca
2+
produced by ATX (100 nM) was antagonized in a concentration-dependent manner by tetrodotoxin. Additional, more direct, evidence for an interaction with voltage-gated sodium channels was derived from the ATX-induced allosteric enhancement of [
3
H]batrachotoxin binding to neurotoxin site 2 of the α subunit of the sodium channel. ATX, moreover, produced a strong synergistic stimulation of [
3
H]batrachotoxin binding in combination with brevetoxin, which is a ligand for neurotoxin site 5 on the voltage-gated sodium channel. Positive allosteric interactions were not observed between ATX and either α-scorpion toxin or the pyrethroid deltamethrin. That ATX interaction with voltage-gated sodium channels produces a gain of function was demonstrated by the concentration-dependent and tetrodotoxin-sensitive stimulation of
22
Na
+
influx in cerebellar granule cells exposed to ATX. Together these results demonstrate that the lipopeptide ATX is an activator of voltage-gated sodium channels. The neurotoxic actions of ATX therefore resemble those of brevetoxins that produce neural insult through depolarization-evoked Na
+
load, glutamate release, relief of Mg
2+
block of NMDA receptors, and Ca
2 +
influx.
Corticosterone levels predict survival probabilities of Galápagos marine iguanas during El Niño events
Authors: Romero L. Michael , Wikelski Martin
Published: July 2002

Plasma levels of corticosterone are often used as a measure of “stress” in wild animal populations. However, we lack conclusive evidence that different stress levels reflect different survival probabilities between populations. Galápagos marine iguanas offer an ideal test case because island populations are affected differently by recurring El Niño famine events, and population-level survival can be quantified by counting iguanas locally. We surveyed corticosterone levels in six populations during the 1998 El Niño famine and the 1999 La Niña feast period. Iguanas had higher baseline and handling stress-induced corticosterone concentrations during famine than feast conditions. Corticosterone levels differed between islands and predicted survival through an El Niño period. However, among individuals, baseline corticosterone was only elevated when body condition dropped below a critical threshold. Thus, the population-level corticosterone response was variable but nevertheless predicted overall population health. Our results lend support to the use of corticosterone as a rapid quantitative predictor of survival in wild animal populations.
Physical and functional interactions between
Drosophila
TRAF2 and Pelle kinase contribute to Dorsal activation
Authors: Shen Baohe , Liu H. , Skolnik Edward Y. , Manley James L.
Published: July 2002

Signaling through the Toll receptor is required for dorsal/ventral polarity in
Drosophila
embryos, and also plays an evolutionarily conserved role in the immune response. Upon ligand binding, Toll appears to multimerize and activate the associated kinase, Pelle. However, the immediate downstream targets of Pelle have not been identified. Here we show that
Drosophila
tumor necrosis factor receptor-associated factor 2 (dTRAF2), a homologue of human TRAF6, physically and functionally interacts with Pelle, and is phosphorylated by Pelle
in vitro
. Importantly, dTRAF2 and Pelle cooperate to activate Dorsal synergistically in cotransfected Schneider cells. Deletion of the C-terminal TRAF domain of dTRAF2 enhances Dorsal activation, perhaps reflecting the much stronger interaction of the mutant protein with phosphorylated, active Pelle. Taken together, our results indicate that Pelle and dTRAF2 physically and functionally interact, and that the TRAF domain acts as a regulator of this interaction. dTRAF2 thus appears to be a downstream target of Pelle. We discuss these results in the context of Toll signaling in flies and mammals.
New isotopic evidence for chronic lead contamination in the San Francisco Bay estuary system: Implications for the persistence of past industrial lead emissions in the biosphere
Authors: Steding Douglas J. , Dunlap Charles E. , Flegal A. Russell
Published: July 2002

Measurements of lead isotope compositions in unfiltered San
Francisco Bay waters from 1989 to 1998 have brought new insights into
the cycling of anthropogenic lead in estuaries. Isotopic compositions
of lead in the shallow (<2 m) southern reach were essentially
invariant (∼90% derived from 1960s–1970s leaded gasoline) during
the study period because of limited hydraulic flushing and the
remobilization of lead from bottom sediments. In contrast, in the
northern reach freshwater flushing from the San Joaquin and Sacramento
rivers produced seasonal and decadal variations in lead isotope
compositions. The seasonal shifts are attributed to advection of soils
containing late 1980s gasoline lead into the bay during winter rains.
Mass balance calculations indicate that only a small fraction (1–10%)
of this leaded gasoline fallout from the late 1980s has been washed out
of the San Joaquin and Sacramento rivers' drainage basin by 1995.
Superimposed on this seasonal cycling was a long-term systematic shift
in the component of gasoline lead expressed in the river systems, with
a small (∼5–10%) decrease in the amount of 1960s–1970s gasoline
lead in river and North Bay waters. The retention of gasoline lead in
the river systems draining into the bay as well as San Francisco Bay
sediments indicates that historic gasoline deposits may remain in the
combined riparian/estuarine system for decades. Such a persistence is
in contraindication to recent reports of rapid (annual) decreases in
lead contamination in other environments, and the link between climate
and contaminant transport suggests local or global climate change will
have an impact on contaminant distribution and fate.
Water clusters: Untangling the mysteries of the liquid, one molecule at a time
Authors: Keutsch Frank N. , Saykally Richard J.
Published: July 2002

Extensive terahertz laser vibration-rotation-tunneling spectra and mid-IR laser spectra have been compiled for several isotopomers of small (dimer through hexamer) water clusters. These data, in conjunction with new theoretical advances, quantify the structures, force fields, dipole moments, and hydrogen bond rearrangement dynamics in these clusters. This new information permits us to systematically untangle the intricacies associated with cooperative hydrogen bonding and promises to lead to a more complete molecular description of the liquid and solid phases of water, including an accurate universal force field.
Local expression of expansin induces the entire process of leaf development and modifies leaf shape
Authors: Pien Stéphane , Wyrzykowska Joanna , McQueen-Mason Simon , Smart Cheryl , Fleming Andrew
Published: July 2002

Expansins are a family of extracellular proteins proposed to play a key role in wall stress relaxation and, thus, in cell and tissue growth. To test the possible function of expansins in morphogenesis, we have developed a technique that allows transient local microinduction of gene expression in transgenic plants. We have used this system to manipulate expansin gene expression in various tissues. Our results indicate that local expansin expression within the meristem induces a developmental program that recapitulates the entire process of leaf formation. Moreover, local transient induction of expansin expression on the flank of developing primordia leads to the induction of ectopic lamina tissue and thus modulation of leaf shape. These data describe an approach for the local manipulation of gene expression and indicate a role for expansin in the control of both leaf initiation and shape. These results are consistent with the action of cell division-independent mechanisms in plant morphogenesis.
Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses
Authors: Bhattacharjee Arindam , Richards William G. , Staunton Jane , Li Cheng , Monti Stefano , Vasa Priya , Ladd Christine , Beheshti Javad , Bueno Raphael , Gillette Michael , Loda Massimo , Weber Griffin , Mark Eugene J. , Lander Eric S. , Wong Wing , Johnson Bruce E. , Golub Todd R. , Sugarbaker David J. , Meyerson Matthew
Published: July 2002

We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients.
Ecological basis of extinction risk in birds: Habitat loss versus human persecution and introduced predators
Authors: Owens Ian P. F. , Bennett Peter M.
Published: July 2002

Understanding the ecological mechanisms that underlie extinction is fundamental to conservation. It is well established that not all taxa are equally vulnerable to extinction, but the reasons for these differences are poorly understood. This may be, in part, because different taxa are threatened by different mechanisms. Theoretically, sources of extinction risk that perturb the balance between fecundity and longevity, such as human persecution and introduced predators, should be particularly hazardous for taxa that have slow rates of population growth. In contrast, sources of extinction risk that reduce niche availability, such as habitat loss, should represent a particular threat to taxa that are ecologically specialized. Here we test these predictions by using a phylogenetic comparative method and a database on 95 families of birds. As theory predicts, extinction risk incurred through persecution and introduced predators is associated with large body size and long generation time but is not associated with degree of specialization, whereas extinction risk incurred through habitat loss is associated with habitat specialization and small body size but not with generation time. These results demonstrate the importance of considering separately the multiple mechanisms that underlie contemporary patterns of extinction. They also reveal why it has previously proven so difficult to identify simple ecological correlates of overall extinction risk.