bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-to-high confinement transition simulations in divertor geometry
Authors: Xu X. Q. , Cohen R. H. , Rognlien T. D. , Myra J. R.
Published: July 2002

Recent results are presented for turbulence in tokamak boundary plasmas and its relationship to the low-to-high confinement (L–H) transition in a realistic divertor geometry. These results are obtained from a three-dimensional (3D) nonlocal electromagnetic turbulence code, which models the boundary plasma using fluid equations for plasma vorticity, density, electron and ion temperatures and parallel momenta. With sources added in the core-edge region and sinks in the scrape-off layer (SOL), the code follows the self-consistent profile evolution together with turbulence. Under DIII-D [Luxon et al., International Conference on Plasma Physics and Controlled Nuclear Fusion (International Atomic Energy Agency, Vienna, 1986), p. 159] tokamak L-mode conditions, the dominant source of turbulence is pressure-gradient-driven resistive X-point modes. These modes are electromagnetic and curvature-driven at the outside mid-plane region but become electrostatic near X-points due to magnetic shear and collisionality. Classical resistive ballooning modes at high toroidal mode number, n, coexist with these modes but are sub-dominant. Results indicate that, as the power is increased, these modes are stabilized by increased turbulence-generated velocity shear, resulting in an abrupt suppression of high-n turbulence and the formation of a pedestal in density and temperature, as is characteristic of the H-mode transition. The sensitivity of the boundary turbulence to the direction of the toroidal field Bt is discussed.
Robustness and flexibility in compact quasiaxial stellarators: Global ideal magnetohydrodynamic stability and energetic particle transport
Authors: Redi M. H. , Diallo A. , Cooper W. A. , Fu G. Y. , Nührenberg C. , Pomphrey N. , Reiman A. H. , Zarnstorff M. C. ,   NCSX Team
Published: July 2002

Concerns about the flexibility and robustness of a compact quasiaxial stellarator design are addressed by studying the effects of varied pressure and rotational transform profiles on expected performance. For thirty, related, fully three-dimensional configurations the global, ideal magnetohydrodynamic (MHD) stability and energetic particle transport are evaluated. It is found that tokamak intuition is relevant to understanding the magnetohydrodynamic stability, with pressure gradient driving terms and shear stabilization controlling both the periodicity preserving, N=0, and the nonperiodicity preserving, N=1, unstable kink modes. Global kink modes are generated by steeply peaked pressure profiles near the half radius and edge localized kink modes are found for plasmas with steep pressure profiles at the edge as well as with edge rotational transform above 0.5. Energetic particle transport is not strongly dependent on these changes of pressure and current (or rotational transform) profiles, although a weak inverse dependence on pressure peaking through the corresponding Shafranov shift is found. While good transport and MHD stability are not anticorrelated in these equilibria, stability only results from a delicate balance of the pressure and shear stabilization forces. A range of interesting MHD behaviors is found for this large set of equilibria, exhibiting similar particle transport properties.
Optical pulse compression to 8 fs at a 5-kHz repetition rate
Authors: Knox W. H. , Fork R. L. , Downer M. C. , Stolen R. H. , Shank C. V. , Valdmanis J. A.
Published: July 2002

Single amplified 40-fs optical pulses are compressed to 8-fs duration at a 5-kHz repetition rate using self-phase modulation in a single-mode optical fiber.
Theoretical model for the oxidation of silicon
Authors: Samalam Vijay K.
Published: July 2002

A theoretical model for the rapid growth of silicon dioxide in a dry oxygen ambient is presented. The model is based on the fact that silicon dioxide has micropores through which the oxygen molecules can travel easily. The theory is compared to experiment and shows good agreement.
Capacitance and conductance deep level transient spectroscopy in field-effect transistors
Authors: Hawkins I. D. , Peaker A. R.
Published: July 2002

An analysis of conductance transients in field-effect transistors for small values of drain-source voltage is presented which enables absolute values of trap concentration to be evaluated. The relationships use parameters which can be easily measured as distinct from the estimated values of mobility profiles used in previously published calculations. Excellent quantitative agreement between capacitance and conductance results on large area gallium arsenide field-effect transistors has been obtained. In addition, conductance deep level transient studies have demonstrated that the method of measurement and analysis can be used for micron and submicron devices which are much too small for capacitive measurements.
Amphoteric defects at the Si-SiO2 interface
Authors: Chang S. T. , Wu J. K. , Lyon S. A.
Published: July 2002

We have investigated the defects generated at the Si-SiO2 interface by x-ray irradiation and Fowler–Nordheim tunneling. When the positive charge trapped in the SiO2 after tunneling at low temperature is annihilated by photoinjected electrons, equal numbers of acceptorlike and donorlike interface states form. One interface state of each type is produced for each trapped positive charge. Similarly, if some interface states are allowed to form after x-ray irradiation, and then the remaining trapped holes are eliminated by photoinjecting electrons at 90 K, equal numbers of acceptorlike and donorlike interface states remain. The data indicate that each trapped positive charge can produce a single amphoteric center, probably a trivalent silicon interfacial defect. These defects account for all of the interface states observed in this study.
High-brightness green-emitting electroluminescent devices with ZnS:Tb,F active layers
Authors: Ogura T. , Mikami A. , Tanaka K. , Taniguchi K. , Yoshida M. , Nakajima S.
Published: July 2002

The dependence of brightness on the concentration ratio of fluorine to terbium was studied in thin-film electroluminescent devices with rf-sputtered ZnS:Tb,F active layers. It was found that the device exhibits a maximum brightness at the concentration ratio of about 1. By optimizing not only the concentration ratio but also the terbium concentration, a brightness more than 300 fL is obtained under 1 kHz pulse excitation.
X-point excitons in AlAs/GaAs superlattices
Authors: Finkman E. , Sturge M. D. , Tamargo M. C.
Published: July 2002

We have found a long-lived emission at low temperatures in AlAs/GaAs superlattices with approximately equal thicknesses of AlAs and GaAs and with periods in the range 18–60 Å. The emission shows the nonexponential time decay characteristic of an indirect exciton made allowed by disorder. The exciton is found to be at the zone boundary, and to consist of a Γ hole localized in the GaAs and an AlAs X-point electron. The disorder is at the AlAs-GaAs interfaces. There is no ‘‘camel’s back’’ in the exciton dispersion.
Generalized model of the isothermal vapor phase epitaxy of (Hg,Cd)Te
Authors: Djuric Zoran , Piotrowsky Jozef
Published: July 2002

A generalized model of the isothermal vapor phase epitaxy of (Hg,Cd)Te is presented, which for the first time enables us to predict the compositional profiles of the layers in dependence on growth parameters (temperature and time of deposition, mercury and inert gas partial pressures in the growth chamber, source to substrate spacing). The model can be applied to both closed and opened tube isothermal vapor phase epitaxy of (Hg,Cd)Te, and it explains quantitatively all the peculiarities of the epitaxial growth using this method. The model is confronted with experimental data, which correspond satisfactorily to the calculations without any fitting parameters.
Concentration dependence of optical emission from sulfur-doped crystalline silicon
Authors: Brown T. G. , Bradfield P. L. , Hall D. G.
Published: July 2002

We report the measured dependence of the near-infrared optical emission from sulfur-related impurity centers in crystalline silicon on the sulfur concentration in the sample. The results suggest that each impurity complex contains only a single sulfur atom. Additional experiments support the possible presence of oxygen in the impurity center. We also report the observation of concentration quenching of the emission and the observation of absorption by the ground state of the impurity complex.
Novel infrared band-aligned superlattice laser
Authors: Yuh Perng-fei , Wang K. L.
Published: July 2002

A novel infrared laser is proposed which uses the intersubband optical transition in a band-aligned superlattice. In this band-aligned superlattice laser, the miniband discontinuity within the conduction of valence band functions as a band offset in the heterojunction structure, and the population inversion is achieved by current injection as in the conventional heterojunction laser. It is more flexible than a heterojunction laser of a quantum well laser since one may tailor the bandwidth and band structures as well as the band gap of the minibands. Also indirect band-gap materials like Si and Ge can be used for lasing in the intersubband transitions. The intersubband optical transition is similar to an atomic two-level system which exhibits low threshold current, and a gain coefficient with weak temperature dependence and a narrow spectrum which is determined only by the line-shape function. These special features make the band-aligned superlattice laser competitive with and perhaps superior to the quantum well dot laser which is not presently feasible.
Resonant level lifetime in GaAs/AlGaAs double-barrier structures
Authors: Bahder Thomas B. , Morrison Clyde A. , Bruno John D.
Published: July 2002

The lifetime of the lowest quasibound state localized between the barriers of a GaAs/AlGaAs double-barrier structure is calculated as a function of barrier and well dimensions. The results are consistent with high-frequency experiments.
High critical currents in Y-Ba-Cu-O superconductors
Authors: Jin S. , Tiefel T. H. , Sherwood R. C. , Davis M. E. , van Dover R. B. , Kammlott G. W. , Fastnacht R. A. , Keith H. D.
Published: July 2002

Melt-textured growth of polycrystalline YBa2Cu3O7−δ superconductor using directional solidification created an essentially 100% dense structure consisting of long, needle- or plate-shaped crystals preferentially aligned parallel to the a-b conduction plane. The new microstructure, which completely replaces the previous granular and random structure in the sintered precursor, exhibits dramatically improved transport Jc values at 77 K of ∼17 000 A/cm2 in zero field and ∼4000 A/cm2 at H=1 T (as compared to ∼500 and ∼1 A/cm2, respectively, for the as-sintered structure), with the severe field dependence of Jc (‘‘weak-link’’ problem) no longer evident in the new melt-textured material. The improvement in Jc is attributed to the combined effects of densification, alignment of crystals, and formation of cleaner grain boundaries. Microstructure and distribution of various phases present in the melt-textured material are discussed in relation to the superconducting properties.
Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium
Authors: Thompson Deborah , Szabo Csilla I. , Mangion Jon , Oldenburg Rogier A. , Odefrey Fabrice , Seal Sheila , Barfoot Rita , Kroeze-Jansema Karin , Teare Dawn , Rahman Nazneen , Renard Hélène ,   KConFab Consortiumf, Mann Graham , Hopper John L. , Buys Saundra S. , Andrulis Irene L. , Senie Ruby , Daly Mary B. , West Dee , Ostrander Elaine A. , Offit Ken , Peretz Tamar , Osorio Ana , Benitez J. , Nathanson Katherine L. , Sinilnikova Olga M. , Olàh Edith , Bignon Yves-Jean , Ruiz Pablo , Badzioch Michael D. , Vasen Hans F. A. , Futreal Andrew P. , Phelan Catherine M. , Narod Steven A. , Lynch Henry T. , Ponder Bruce A. J. , Eeles Ros A. , Meijers-Heijboer Hanne , Stoppa-Lyonnet Dominique , Couch Fergus J. , Eccles Diana M. , Evans D. Gareth , Chang-Claude Jenny , Lenoir Gilbert , Weber Barbara L. , Devilee Peter , Easton Douglas F. , Goldgar David E. , Stratton Michael R.
Published: July 2002

The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate “BRCA3” locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (α) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu
et al.
[(2000)
Proc. Natl. Acad. Sci. USA
97, 9603–9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (α = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu
et al.
(0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at α = 0.65 was −11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.
Behavioral inferences from the Skhul/Qafzeh early modern human hand remains
Authors: Niewoehner Wesley A.
Published: July 2002

Two groups of humans are found in the Near East ≈100,000 years
ago, the late archaic Neanderthals and the early modern Skhul/Qafzeh
humans. Observations that Neanderthals were more heavily muscled, had
stronger upper-limb bones, and possessed unusual shapes and
orientations of some upper-limb joint complexes relative to the
Skhul/Qafzeh hominids, have led some researchers to conclude that
significant between-group upper-limb-related behavioral differences
must have been present, despite the association of the two groups with
similar Middle Paleolithic archeological complexes. A three-dimensional
morphometric analysis of the hand remains of the Skhul/Qafzeh
hominids, Neanderthals, early and late Upper Paleolithic humans, and
Holocene humans supports the dichotomy. The Skhul/Qafzeh
carpometacarpal remains do not have any unique morphologies relative to
the other fossil samples remains examined. However, in the functionally
significant metacarpal 1 and 3 bases they resemble Upper Paleolithic
humans, not Neanderthals. Furthermore, the Skhul/Qafzeh sample
differs significantly from the Neanderthals in many other aspects of
hand functional anatomy. Given the correlations between changes in tool
technologies and functional adaptations seen in the hands of Upper
Paleolithic humans, it is concluded that the Skhul/Qafzeh hand
remains were adapted to Upper Paleolithic-like manipulative
repertoires. These results support the inference of significant
behavioral differences between Neanderthals and the Skhul/Qafzeh
hominids and indicate that a significant shift in human manipulative
behaviors was associated with the earliest stages of the emergence of
modern humans.
Zinc metallothionein imported into liver mitochondria modulates respiration
Authors: Ye Bin , Maret Wolfgang , Vallee Bert L.
Published: July 2002

Metallothionein (MT) localizes in the intermembrane space
of liver mitochondria as well as in the cytosol and nucleus. Incubation
of intact liver mitochondria with physiological, micromolar
concentrations of MT leads to the import of MT into the mitochondria
where it inhibits respiration. This activity is caused by the
N-terminal β-domain of MT; in this system, the
isolated C-terminal α-domain is inactive. Free zinc inhibits
respiration at concentrations commensurate with the zinc content of
either MT or the isolated β-domain, indicating that MT inhibition
involves zinc delivery to mitochondria. Respiratory inhibition of
uncoupled mitochondria identifies the electron transfer chain as the
primary site of inhibition. The apoform of MT, thionein, is an
endogenous chelating agent and activates zinc-inhibited
respiration with a 1:1 stoichiometry ([zinc binding
sites]/[zinc]). Carbamoylation of the lysines of MT significantly
attenuates the inhibitory effect, suggesting that these residues are
critical for the passage of MT through the outer mitochondrial
membrane. Such an import pathway has been proposed for other proteins
that also lack a mitochondrial targeting sequence, e.g., apocytochrome
c
, and possibly Cox17, a mitochondrial copper chaperone
that is the only protein known so far to exhibit significant primary
sequence homology to MT. The presence and respiratory inhibition of MT
in liver, but not heart, mitochondria suggest a hitherto unknown
biological modulating activity of MT in cellular respiration and energy
metabolism in a tissue-specific manner.
Framing effects and risky decisions in starlings
Authors: Marsh Barnaby , Kacelnik Alex
Published: July 2002

Animals are predominantly risk prone toward reward delays and risk averse toward reward amounts. Humans in turn tend to be risk-seeking for losses and risk averse for gains. To explain the human results, Prospect Theory postulates a convex utility for losses and concave utility for gains. In contrast, Scalar Utility Theory (SUT) explains the animal data by postulating that the cognitive representation of outcomes follows Weber's Law, namely that the spread of the distribution of expected outcomes is proportional to its mean. SUT also would explain human results if utility (even if it is linear on expected outcome) followed Weber's Law. We present an experiment that simulates losses and gains in a bird, the European Starling, to test the implication of SUT that risk proneness/aversion should extend to any aversive/desirable dimension other than time and amount of reward. Losses and gains were simulated by offering choices of fixed vs. variable outcomes with lower or higher outcomes than what the birds expected. The subjects were significantly more risk prone for losses than for gains but, against expectations, they were not significantly risk averse toward gains. The results are thus, in part, consistent with Prospect Theory and SUT and show that risk attitude in humans and birds may obey a common fundamental principle.
A nonpetide integrin antagonist can inhibit epithelial cell ingestion of
Streptococcus pyogenes
by blocking formation of integrin α5β1-fibronectin-M1 protein complexes
Authors: Cue David , Southern Sarka O. , Southern Peter J. , Prabhakar Jadhar , Lorelli William , Smallheer Joanne M. , Mousa Shaker A. , Cleary P. Patrick
Published: July 2002

Streptococcus pyogenes
can be efficiently internalized
by a variety of human epithelial cells. β-lactam antibiotics,
commonly used to treat
S. pyogenes
infections, do not
readily permeate mammalian cells. There is growing evidence that the
ability of streptococci to enter host cells contributes to the frequent
failure of antibiotics to eradicate the organism from infected
individuals. Recent studies have suggested that host cell entry
requires the formation of a complex of a bacterial fibronectin (Fn)
binding protein (e.g., M1 protein or protein F1/SfbI), human Fn, and
the epithelial cell Fn receptor, integrin α5β1. We report here that
a low molecular weight, nonpeptide antagonist of integrin α5β1,
SJ755, can inhibit internalization of streptococci by primary human
tonsillar epithelial cells and immortalized human epithelial (A549)
cells, thus increasing the extent of bacterial killing by antibiotics.
SJ755 blocked Fn binding by human tonsillar epithelial and A549 cells,
suggesting that integrin α5β1 is the major Fn receptor expressed by
both cell types. SJ755 did not affect Fn binding by purified M1 protein
or M1
+
bacteria. Purified M1 protein failed to associate
with integrin α5β1 unless the integrin had been prebound by Fn.
Also, SJ755 blocked formation of α5β1-Fn-M1 complexes
in
vitro
. These results support the previous proposal that Fn
functions as a molecular bridge between M1 protein and integrin
α5β1. Furthermore, these results suggest that integrin antagonists
may enhance the efficacy of antibiotics in treatment of
S.
pyogenes
infections.
Localization and regulation of GLUTx1 glucose transporter in the hippocampus of streptozotocin diabetic rats
Authors: Reagan Lawrence P. , Gorovits Naira , Hoskin Elena K. , Alves Stephen E. , Katz Ellen B. , Grillo Claudia A. , Piroli Gerardo G. , McEwen Bruce S. , Charron Maureen J.
Published: July 2002

We describe the localization of the recently identified glucose
transporter GLUTx1 and the regulation of GLUTx1 in the hippocampus of
diabetic and control rats. GLUTx1 mRNA and protein exhibit a unique
distribution when compared with other glucose transporter isoforms
expressed in the rat hippocampus. In particular, GLUTx1 mRNA was
detected in hippocampal pyramidal neurons and granule neurons of the
dentate gyrus as well as in nonprincipal neurons. With
immunohistochemistry, GLUTx1 protein expression is limited to neuronal
cell bodies and the most proximal dendrites, unlike GLUT3 expression
that is observed throughout the neuropil. Immunoblot analysis of
hippocampal membrane fractions revealed that GLUTx1 protein expression
is primarily localized to the intracellular compartment and exhibits
limited association with the plasma membrane. In streptozotocin
diabetic rats compared with vehicle-treated controls, quantitative
autoradiography showed increased GLUTx1 mRNA levels in pyramidal
neurons and granule neurons; up-regulation of GLUTx1 mRNA also was
found in nonprincipal cells, as shown by single-cell emulsion
autoradiography. In contrast, diabetic and control rats expressed
similar levels of hippocampal GLUTx1 protein. These results indicate
that GLUTx1 mRNA and protein have a unique expression pattern in rat
hippocampus and suggest that streptozotocin diabetes increases
steady-state mRNA levels in the absence of concomitant increases in
GLUTx1 protein expression.
Heterogeneous transcription of an indoleacetic acid biosynthetic gene in
Erwinia herbicola
on plant surfaces
Authors: Brandl M. T. , Quiñones B. , Lindow S. E.
Published: July 2002

We investigated the spatial pattern of expression of
ipdC
, a plant inducible gene involved in indoleacetic
acid biosynthesis in
Erwinia herbicola
, among individual
cells on plants to gain a better understanding of the role of this
phenotype in the epiphytic ecology of bacteria and the factors involved
in the regulation of
ipdC
. Nonpathogenic
E.
herbicola
strain 299R harboring a transcriptional fusion of
ipdC
to
gfp
was inoculated onto bean
plants, recovered from individual leaves 48 h after inoculation,
and subjected to fluorescence
in situ
hybridization
using a 16S rRNA oligonucleotide probe specific to strain 299R.
Epifluorescence images captured through a rhodamine filter were used to
distinguish the 5carboxytetramethylrhodamine-labeled cells of
strain 299R from other leaf microflora. Quantification of the green
fluorescence intensity of individual cells by analysis of digital
images revealed that about 65% of the 299R cells recovered from bean
leaves had higher
ipdC
expression than in culture.
Additionally, 10% of the cells exhibited much higher levels of green
fluorescence than the median fluorescence intensity, indicating that
they are more heterogeneous with respect to
ipdC
expression on plants than in culture. Examination of 299R cells
in situ
on leaf surfaces by confocal laser scanning
microscopy after fluorescence
in situ
hybridization of
cells on leaf samples showed that even cells that were in close
proximity exhibited dramatically different green fluorescence
intensities, and thus, were in a physical or chemical microenvironment
that induced differential expression of
ipdC
.
Brownian flocculation of polymer colloids in the presence of a secondary minimum
Authors: Schowalter William R. , Eidsath Alec B.
Published: July 2002

Most analyses of Brownian flocculation apply to conditions where
London–van der Waals attractive forces cause particles to be strongly
bound in a deep interparticle potential well. In this paper, results
are reported that show the interaction between primary- and
secondary-minimum flocculation when the interparticle potential curve
reflects both attractive and electrostatic repulsive forces. The
process is highly time-dependent because of transfer of particles from
secondary- to primary-minimum flocculation. Essential features of the
analysis are corroborated by experiments with 0.80-μm polystyrene
spheres suspended in aqueous solutions of NaCl over a range of ionic
strengths. In all cases, experiments were restricted to the initial
stage of coagulation, where singlets and doublets predominate.
Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force
Authors: Evans Evan , Leung Andrew , Hammer Dan , Simon Scott
Published: July 2002

Carbohydrate–protein bonds interrupt the rapid flow of leukocytes
in the circulation by initiation of rolling and tethering at vessel
walls. The cell surface carbohydrate ligands are glycosylated proteins
like the mucin P-selectin glycoprotein ligand-1 (PSGL-1), which bind
ubiquitously to the family of E-, P-, and L-selectin proteins in
membranes of leukocytes and endothelium. The current view is that
carbohydrate–selectin bonds dissociate a few times per second, and the
unbinding rate increases weakly with force. However, such studies have
provided little insight into how numerous hydrogen bonds, a
Ca
2+
metal ion bond, and other interactions contribute to
the mechanical strength of these attachments. Decorating a force probe
with very dilute ligands and controlling touch to achieve rare
single-bond events, we have varied the unbinding rates of
carbohydrate–selectin bonds by detachment with ramps of force/time
from 10 to 100,000 pN/sec. Testing PSGL-1, its outer 19 aa (19FT),
and sialyl Lewis
X
(sLe
X
) against L-selectin
in vitro
on glass microspheres and
in
situ
on neutrophils, we found that the unbinding rates followed
the same dependence on force and increased by nearly 1,000-fold as
rupture forces rose from a few to ≈200 pN. Plotted on a logarithmic
scale of loading rate, the rupture forces reveal two prominent energy
barriers along the unbinding pathway. Strengths above 75 pN arise from
rapid detachment (<0.01 sec) impeded by an inner barrier that requires
a Ca
2+
bond between a single sLe
X
and the
lectin domain. Strengths below 75 pN occur under slow detachment
(>0.01 sec) impeded by the outer barrier, which appears to involve an
array of weak (putatively hydrogen) bonds.
Predicted highly expressed and putative alien genes of
Deinococcus radiodurans
and implications for resistance to ionizing radiation damage
Authors: Karlin Samuel , Mrázek Jan
Published: July 2002

Predicted highly expressed (PHX) and putative alien genes
determined by codon usages are characterized in the genome of
Deinococcus radiodurans
(strain R1).
Deinococcus
radiodurans
(DEIRA) can survive very high doses of ionizing
radiation that are lethal to virtually all other organisms. It has been
argued that DEIRA is endowed with enhanced repair systems that provide
protection and stability. However, predicted expression levels of DNA
repair proteins with the exception of RecA tend to be low and do not
distinguish DEIRA from other prokaryotes. In this paper, the capability
of DEIRA to resist extreme doses of ionizing and UV radiation is
attributed to an unusually high number of PHX chaperone/degradation,
protease, and detoxification genes. Explicitly, compared with all
current complete prokaryotic genomes, DEIRA contains the greatest
number of PHX detoxification and protease proteins. Other sources of
environmental protection against severe conditions of UV radiation,
desiccation, and thermal effects for DEIRA are the several S-layer
(surface structure) PHX proteins. The top PHX gene of DEIRA is the
multifunctional tricarboxylic acid (TCA) gene aconitase, which, apart
from its role in respiration, also alerts the cell to oxidative damage.
The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins
Authors: Henis-Korenblit Sivan , Shani Gidi , Sines Tal , Marash Lea , Shohat Galit , Kimchi Adi
Published: July 2002

Apoptosis is characterized by a translation switch from capdependent to internal ribosome entry site (IRES)-mediated protein translation. During apoptosis, several members of the eukaryotic initiation factor (eIF)4G family are cleaved specifically by caspases. Here we investigated which of the caspase-cleaved eIF4G family members could support cap-independent translation through IRES elements that retain activity in the dying cell. We focused on two major fragments arising from the cleavage of eIF4GI and death-associated protein 5 (DAP5) proteins (eIF4GI M-FAG/p76 and DAP5/p86, respectively), because they are the only potential candidates to preserve the minimal scaffold function needed to mediate translation. Transfection-based experiments in cell cultures indicated that expression of DAP5/p86 in cells stimulated protein translation from the IRESs of c-Myc, Apaf-1, DAP5, and XIAP. In contrast, these IRESs were refractory to the ectopically expressed eIF4GI M-FAG/p76. Furthermore, our study provides
in vivo
evidence that the caspase-mediated removal of the C-terminal tail of DAP5/p97 relieves an inhibitory effect on the protein's ability to support cap-independent translation through the DAP5 IRES. Altogether, the data suggest that DAP5 is a caspase-activated translation factor that mediates translation through a repertoire of IRES elements, supporting the translation of apoptosis-related proteins.
The phylogeny of closely related species as revealed by the genealogy of a speciation gene,
Odysseus
Authors: Ting Chau-Ti , Tsaur Shun-Chern , Wu Chung-I
Published: July 2002

Molecular differentiation between races or closely related species is often incongruent with the reproductive divergence of the taxa of interest. Shared ancient polymorphism and/or introgression during secondary contact may be responsible for the incongruence. At loci contributing to speciation, these two complications should be minimized (1, 2); hence, their variation may more faithfully reflect the history of the species' reproductive differentiation. In this study, we analyzed DNA polymorphism at the
Odysseus
(
OdsH
) locus of hybrid sterility between
Drosophila mauritiana
and
Drosophila simulans
and were able to verify such a prediction. Interestingly, DNA variation only a short distance away (1.8 kb) appears not to be influenced by the forces that shape the recent evolution of the
OdsH
coding region. This locus thus may represent a test case of inferring phylogeny of very closely related species.
A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9
Authors: Dash Ajeeta B. , Williams Ifor R. , Kutok Jeffery L. , Tomasson Michael H. , Anastasiadou Ema , Lindahl Kathleen , Li Shaoguang , Van Etten Richard A. , Borrow Julian , Housman David , Druker Brian , Gilliland D. Gary
Published: July 2002

Constitutive activation of tyrosine kinases, such as the BCR/ABL fusion associated with t(9;22)(q34;q22), is a hallmark of chronic myeloid leukemia (CML) syndromes in humans. Expression of BCR/ABL is both necessary and sufficient to cause a chronic myeloproliferative syndrome in murine bone marrow transplantation models, and absolutely depends on kinase activity. Progression of CML to acute leukemia (blast crisis) in humans has been associated with acquisition of secondary chromosomal translocations, including the t(7;11)(p15;p15) resulting in the NUP98/HOXA9 fusion protein. We demonstrate that BCR/ABL cooperates with NUP98/HOXA9 to cause blast crisis in a murine model. The phenotype depends both on expression of BCR/ABL and NUP98/HOXA9, but tumors retain sensitivity to the ABL inhibitor STI571
in vitro
and
in vivo
. This paradigm is applicable to other constitutively activated tyrosine kinases such as TEL/PDGFβR. These experiments document cooperative effects between constitutively activated tyrosine kinases, which confer proliferative and survival properties to hematopoietic cells, with mutations that impair differentiation, such as the NUP98/HOXA9, giving rise to the acute myeloid leukemia (AML) phenotype. Furthermore, these data indicate that despite acquisition of additional mutations, CML blast crisis cells retain their dependence on BCR/ABL for proliferation and survival.
Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in
Escherichia coli
Authors: Pham Phuong , Rangarajan Savithri , Woodgate Roger , Goodman Myron F.
Published: July 2002

DNA polymerase V, composed of a heterotrimer of the DNA damage-inducible UmuC and UmuD

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proteins, working in conjunction with RecA, single-stranded DNA (ssDNA)-binding protein (SSB), β sliding clamp, and γ clamp loading complex, are responsible for most SOS lesion-targeted mutations in
Escherichia coli
, by catalyzing translesion synthesis (TLS). DNA polymerase II, the product of the damage-inducible
polB
(
dinA
) gene plays a pivotal role in replication-restart, a process that bypasses DNA damage in an error-free manner. Replication-restart takes place almost immediately after the DNA is damaged (≈2 min post-UV irradiation), whereas TLS occurs after pol V is induced ≈50 min later. We discuss recent data for pol V-catalyzed TLS and pol II-catalyzed replication-restart. Specific roles during TLS for pol V and each of its accessory factors have been recently determined. Although the precise molecular mechanism of pol II-dependent replication-restart remains to be elucidated, it has recently been shown to operate in conjunction with RecFOR and PriA proteins.
Corepressor-induced organization and assembly of the biotin repressor: A model for allosteric activation of a transcriptional regulator
Authors: Weaver Larry H. , Kwon Keehwan , Beckett Dorothy , Matthews Brian W.
Published: July 2002

The
Escherichia coli
biotin repressor binds to the
biotin operator to repress transcription of the biotin biosynthetic
operon. In this work, a structure determined by x-ray crystallography
of a complex of the repressor bound to biotin, which also functions as
an activator of DNA binding by the biotin repressor (BirA), is
described. In contrast to the monomeric aporepressor, the complex is
dimeric with an interface composed in part of an extended β-sheet.
Model building, coupled with biochemical data, suggests that this is
the dimeric form of BirA that binds DNA. Segments of three surface
loops that are disordered in the aporepressor structure are located in
the interface region of the dimer and exhibit greater order than was
observed in the aporepressor structure. The results suggest that the
corepressor of BirA causes a disorder-to-order transition that is a
prerequisite to repressor dimerization and DNA binding.
Retinoids down-regulate telomerase and telomere length in a pathway distinct from leukemia cell differentiation
Authors: Pendino Frédéric , Flexor Maria , Delhommeau François , Buet Dorothée , Lanotte Michel , Ségal-Bendirdjian Evelyne
Published: July 2002

Human telomerase, a cellular reverse transcriptase (hTERT), is a
nuclear ribonucleoprotein enzyme complex that catalyzes the synthesis
and extension of telomeric DNA. This enzyme is specifically activated
in most malignant tumors but is usually inactive in normal somatic
cells, suggesting that telomerase plays an important role in cellular
immortalization and tumorigenesis. Terminal maturation of tumor cells
has been associated with the repression of telomerase activity. Using
maturation-sensitive and -resistant NB4 cell lines, we analyzed the
pattern of telomerase expression during the therapeutic treatment of
acute promyelocytic leukemia (APL) by retinoids. Two pathways leading
to the down-regulation of hTERT and telomerase activity were
identified. The first pathway results in a rapid down-regulation of
telomerase that is associated with retinoic acid receptor
(RAR)-dependent maturation of NB4 cells. Furthermore, during NB4 cell
maturation, obtained independently of RAR by retinoic X receptor
(RXR)-specific agonists (rexinoids), no change in telomerase activity
was observed, suggesting that hTERT regulation requires a specific
signaling and occurs autonomously. A second pathway of hTERT
regulation, identified in the RAR-responsive, maturation-resistant
NB4-R1 cell line, results in a down-regulation of telomerase that
develops slowly during two weeks of all-
trans
retinoic
acid (ATRA) treatment. This pathway leads to telomere shortening,
growth arrest, and cell death, all events that are overcome by ectopic
expression of hTERT. These findings demonstrate a clear and full
dissociation between the process of tumor cell maturation and the
regulation of hTERT mRNA expression and telomerase activity by
retinoids. We propose telomerase expression as an efficient and
selective target of retinoids in the therapy of tumors.
A polymorphic gene nested within an intron of the
tau
gene: Implications for Alzheimer's disease
Authors: Conrad Chris , Vianna Cintia , Freeman Melissa , Davies Peter
Published: July 2002

A previously undescribed gene, Saitohin (STH), has been discovered in the intron between exons 9 and 10 of the human
tau
gene. STH is an intronless gene that encodes a 128-aa protein with no clear homologs. The tissue expression of STH is similar to
tau
, a gene that is implicated in many neurodegenerative disorders. In humans, a single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in STH and was used in a case control study. The Q7R polymorphism appears to be over-represented in the homozygous state in late onset Alzheimer's disease subjects.
Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase that prevents starch biosynthesis
Authors: Rodríguez-López Milagros , Baroja-Fernández Edurne , Zandueta-Criado Aitor , Pozueta-Romero Javier
Published: July 2002

A distinct phosphodiesterasic activity (EC 3.1.4) was found in both mono- and dicotyledonous plants that catalyzes the hydrolytic breakdown of ADPglucose (ADPG) to produce equimolar amounts of glucose-1-phosphate and AMP. The enzyme responsible for this activity, referred to as ADPG pyrophosphatase (AGPPase), was purified over 1,100-fold from barley leaves and subjected to biochemical characterization. The calculatedKeq′ (modified equilibrium constant) value for the ADPG hydrolytic reaction at pH 7.0 and 25°C is 110, and its standard-state free-energy change value (ΔG′) is −2.9 kcal/mol (1 kcal = 4.18 kJ). Kinetic analyses showed that, although AGPPase can hydrolyze several low-molecular weight phosphodiester bond-containing compounds, ADPG proved to be the best substrate (Km= 0.5 mM). Piand phosphorylated compounds such as 3-phosphoglycerate, PPi, ATP, ADP, NADP+, and AMP are inhibitors of AGPPase. Subcellular localization studies revealed that AGPPase is localized exclusively in the plastidial compartment of cultured cells of sycamore (Acer pseudoplatanusL.), whereas it occurs both inside and outside the plastid in barley endosperm. In this paper, evidence is presented that shows that AGPPase, whose activity declines concomitantly with the accumulation of starch during development of sink organs, competes with starch synthase (ADPG:1,4-α-d-glucan 4-α-d-glucosyltransferase; EC2.4.1.21) for ADPG, thus markedly blocking the starch biosynthesis.
Crystal structure of the regulatory subunit H of the V-type ATPase of
Saccharomyces cerevisiae
Authors: Sagermann Martin , Stevens Tom H. , Matthews Brian W.
Published: July 2002

In contrast to the F-type ATPases, which use a proton gradient to generate ATP, the V-type enzymes use ATP to actively transport protons into organelles and extracellular compartments. We describe here the structure of the H-subunit (also called Vma13p) of the yeast enzyme. This is the first structure of any component of a V-type ATPase. The H-subunit is not required for assembly but plays an essential regulatory role. Despite the lack of any apparent sequence homology the structure contains five motifs similar to the so-called HEAT or armadillo repeats seen in the importins. A groove, which is occupied in the importins by the peptide that targets proteins for import into the nucleus, is occupied here by the 10 amino-terminal residues of subunit H itself. The structural similarity suggests how subunit H may interact with the ATPase itself or with other proteins. A cleft between the amino- and carboxyl-terminal domains also suggests another possible site of interaction with other factors.
A role for CD36 in the regulation of dendritic cell function
Authors: Urban Britta C. , Willcox Nick , Roberts David J.
Published: July 2002

Dendritic cells (DC) are crucial for the induction of immune responses and thus an inviting target for modulation by pathogens. We have previously shown thatPlasmodium falciparum-infected erythrocytes inhibit the maturation of DCs. IntactP. falciparum-infected erythrocytes can bind directly to CD36 and indirectly to CD51. It is striking that these receptors, at least in part, also mediate the phagocytosis of apoptotic cells. Here we show that antibodies against CD36 or CD51, as well as exposure to early apoptotic cells, profoundly modulate DC maturation and function in response to inflammatory signals. Although modulated DCs still secrete tumor necrosis factor-α, they fail to activate T cells and now secrete IL-10. We therefore propose that intactP. falciparum-infected erythrocytes and apoptotic cells engage similar pathways regulating DC function. These findings may have important consequences for the treatment of malaria and may suggest strategies for modulating pathological immune responses in autoimmune diseases.
Hepatitis C virus replication is directly inhibited by IFN-α in a full-length binary expression system
Authors: Chung Raymond T. , He Wenping , Saquib Afroz , Contreras Ana M. , Xavier Ramnik J. , Chawla Ashish , Wang Timothy C. , Schmidt Emmett V.
Published: July 2002

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis,
cirrhosis, and hepatocellular carcinoma. The absence of culture systems
permissive for HCV replication has presented a major bottleneck to
antiviral development. We sought to recapitulate the early steps in the
life cycle of HCV by means of DNA-based expression of viral genomic
sequences. Here we report expression of replicating HCV RNA by using a,
to our knowledge, novel binary expression system in which cells were
transfected with a T7 polymerase-driven full-length HCV cDNA plasmid
containing a
cis
-acting hepatitis Δ ribozyme to
control 3′ cleavage, and infected with vaccinia-T7 polymerase. HCV
genomic and replicative strand synthesis, in addition to protein
synthesis, was detectable and depended on full-length HCV sequences.
Moreover, the system was capable of generating HCV RNA quasispecies,
consistent with the action of the low-fidelity HCV NS5B RNA polymerase.
IFN-α, but not ribavirin, directly inhibited the viral replicative
cycle in these cells, identifying the virus itself and not solely the
immune system as a direct target of IFN action. The availability of a
cell-based test for viral replication will facilitate screening of
inhibitory compounds, analysis of IFN-resistance mechanisms, and
analysis of virus–host cell interactions.
Transcriptional repression of euchromatic genes by
Drosophila
heterochromatin protein 1 and histone modifiers
Authors: Hwang Kyu-Kye , Eissenberg Joel C. , Worman Howard J.
Published: July 2002

In
Drosophila,
heterochromatin protein 1 (HP1)
suppresses the expression of euchromatic genes that are artificially
translocated adjacent to heterochromatin by expanding heterochromatin
structure into neighboring euchromatin. The purpose of this study was
to determine whether HP1 functions as a transcriptional repressor in
the absence of chromosome rearrangements. Here, we show that
Drosophila
HP1 normally represses the expression of four
euchromatic genes in a dosage-dependent manner. Three genes regulated
by HP1 map to cytological region 31 of chromosome 2, which is
immunostained by anti-HP1 antibodies in the salivary gland. The
repressive effect of HP1 is decreased by mutation in
Su(var)3–9,
whose mammalian orthologue encodes a
histone H3 methyltransferase and mutation in
Su(var)2–1,
which is correlated with histone H4
deacetylation. These data provide genetic evidence that an HP1-family
protein represses the expression of euchromatic genes in a metazoan,
and that histone modifiers cooperate with HP1 in euchromatic gene
repression.
Crystal structure of the central region of bovine fibrinogen (E
5
fragment) at 1.4-Å resolution
Authors: Madrazo Joel , Brown Jerry H. , Litvinovich Sergei , Dominguez Roberto , Yakovlev Sergei , Medved Leonid , Cohen Carolyn
Published: July 2002

The high-resolution crystal structure of the N-terminal central region of bovine fibrinogen (a 35-kDa E
5
fragment) reveals a remarkable dimeric design. The two halves of the molecule bond together at the center in an extensive molecular “handshake” by using both disulfide linkages and noncovalent contacts. On one face of the fragment, the Aα and Bβ chains from the two monomers form a funnel-shaped domain with an unusual hydrophobic cavity; here, on each of the two outer sides there appears to be a binding site for thrombin. On the opposite face, the N-terminal γ chains fold into a separate domain. Despite the chemical identity of the two halves of fibrinogen, an unusual pair of adjacent disulfide bonds locally constrain the two γ chains to adopt different conformations. The striking asymmetry of this domain may promote the known supercoiling of the protofibrils in fibrin. This information on the detailed topology of the E
5
fragment permits the construction of a more detailed model than previously possible for the critical trimolecular junction of the protofibril in fibrin.
A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors
Authors: Ste. Marie Linda , Miura Grant I. , Marsh Donald J. , Yagaloff Keith , Palmiter Richard D.
Published: July 2002

Melanocortin-4 receptor (Mc4r)-null mice exhibit late-onset
obesity. To determine whether aberrant metabolism contributes to the
obesity, food consumption by Mc4r-null mice was restricted to (pair-fed
to) that consumed by wild-type (WT) mice. Pair-fed Mc4r-null females
maintained body weights intermediate to that of WT and nonpair-fed
Mc4r-null females, whereas pairfeeding normalized the body weights of
Mc4r-null male mice. Fat pad and circulating leptin levels were
elevated in both male and female pair-fed Mc4r-null mice compared with
WT mice. Oxygen consumption of Mc4r-null mice with similar body weights
as WT controls was reduced by 20%. Locomotor activity of young
nonobese Mc4r-null males was significantly lower than that of WT males;
however, locomotion of young nonobese females was normal. Core body
temperature of Mc4r-null mice was normal, and they responded normally
to cold exposure. Young nonobese Mc4r-null females were unable to
induce uncoupling protein 1 (UCP1) in brown adipose tissue in response
to peripheral leptin administration, whereas UCP1 mRNA was increased by
60% in the WT females. These results indicate that Mc4r deficiency
enhances caloric efficiency, similar to that seen in the agouti obesity
syndrome and in melanocortin-3 receptor-null mice.