bluuebunny/crossref_metadata_2025 huggingface dataset:
Properties of (Ge2)x(GaAs)1−x alloys grown by molecular beam epitaxy
Authors: Banerjee Indrajit , Chung Don W. , Kroemer Herbert
Published: July 2002

Single-crystalline (Ge2)x(GaAs)1−x alloys have been grown by molecular beam epitaxy on GaAs (100) substrates at substrate temperatures of 550 and 430 °C. The structure of these alloys has been studied using transmission electron microscopy. We observe that growths done at 550 °C show a compositional phase separation, within a structurally single-crystalline lattice, into Ge-rich and GaAs-rich domains whose sizes are of the order of 100 Å. Growths at 430 °C appear to be both single phase and single crystalline. Room-temperature Hall measurements on the single-phase alloys show them to be n type.
Enhancement of lateral solid phase epitaxial growth in evaporated amorphous Si films by phosphorus implantation
Authors: Yamamoto Hiroshi , Ishiwara Hiroshi , Furukawa Seijiro
Published: July 2002

Characteristics of lateral solid phase epitaxial (L-SPE) growth and random crystallization in amorphous Si films, which were deposited on (100) Si substrates with SiO2 patterns at elevated substrate temperature and amorphized by subsequent Si+ or P+ ion implantation, were investigated. It was found from Nomarski optical microscopy that phosphorus doping is effective to enhance the L-SPE growth rate and to reduce the random nucleation rate. Owing to these two effects, the maximum L-SPE length of about 24 μm was obtained in the film doped with 3×1020 P atoms/cm3 after 8-h annealing at 600 °C, which was about six times longer than that in the undoped films.
Clustering of molecular hydrogen in fused silica
Authors: Graebner J. E. , Lemaire P. J. , Allen L. C. , Haemmerle W. H.
Published: July 2002

Molecular hydrogen H2 in glass optical fibers has been detected calorimetrically at the 50 ppm level by monitoring the ortho-para conversion of H2 at low temperatures (T<1 K). The number of H2 molecules is determined and information about the local configuration can be inferred. It is concluded that the majority of the H2 is located in strings or very small clusters of two or three molecules each, rather than being uniformly distributed as isolated molecules.
Small-period electromagnet wigglers for free-electron lasers
Authors: Granatstein V. L. , Destler W. W. , Mayergoyz I. D.
Published: July 2002

A new configuration for wiggler magnets compatible with free-electron laser (FEL) deployment is described and demonstrated experimentally. The configuration is simple and inexpensive to fabricate and allows for continuous control of magnetic field amplitude. Because ferromagnetic cores are used, the wiggler fields are strong (∼0.1 T), while the wiggler period can be very small, on the order of 1 mm. It is shown that high power millimeter and submillimeter FEL’s could be built using such wigglers together with sheet electron beams, and that they would have substantially reduced electron energy requirements when compared with FEL’s employing larger period wigglers.
Non-alloyed ohmic contact to n-GaAs by solid phase epitaxy
Authors: Marshall E. D. , Chen W. X. , Wu C. S. , Lau S. S. , Kuech T. F.
Published: July 2002

A non-alloyed ohmic contact to n-type GaAs has been demonstrated. The technique of solid phase epitaxy through a transport medium has been used to obtain a metal/Ge(n+, epi)/GaAs(n, 〈100〉) heterostructure. The resulting contact displays a smooth surface and low contact resistivity (∼10−6–10−5 Ω cm2) when compared with standard Au-Ge contacts on n-GaAs with similar doping concentrations (∼1018/cm3).
Surface plasmon enhanced quantum efficiency of metal-insulator-semiconductor junctions in the visible
Authors: Berthold K. , Beinstingl W. , Berger R. , Gornik E.
Published: July 2002

Narrowband photosignals with quantum efficiencies up to 30% are observed on Al-SiO2-p-Si junctions. The frequency selective photosignals are due to surface plasmon polaritons confined to the metal-air interface excited by grating coupling. The best results are achieved with Ag-Al-SiO2-p-Si junctions providing a 12-nm linewidth and a signal to background ratio of 7:1 at a wavelength of 632.8 nm. The spectral sensitivity of these photodetectors is tunable over the whole visible spectrum either by a variation of the tilt angle or by a dielectric coating.
High performance GaInAsSb/GaSb p-n photodiodes for the 1.8–2.3 μm wavelength range
Authors: Srivastava A. K. , DeWinter J. C. , Caneau C. , Pollack M. A. , Zyskind J. L.
Published: July 2002

GaInAsSb/GaSb p-n heterojunction photodiodes prepared by liquid phase epitaxy are described. The low net acceptor concentration obtained by Te compensation of the quaternary layer permits a room-temperature external quantum efficiency of 67±5% to be achieved at a wavelength of 2.2 μm.
Four-channel AlGaAs/GaAs optoelectronic integrated transmitter array
Authors: Kuno M. , Sanada T. , Nobuhara H. , Makiuchi M. , Fujii T. , Wada O. , Sakurai T.
Published: July 2002

A monolithic four-channel optical transmitter at 0.8 μm wavelength has been fabricated. This has been achieved by using AlGaAs/GaAs optoelectronic integrated circuit (OEIC) approach. The OEIC chip contains four transmitter channels and each channel is composed of a graded-index waveguide separate-confinement heterostructure single quantum well laser, a monitor photodiode, and a laser driver circuit. The characteristics have been shown to be very uniform over four channels and pulse modulation responses over 1 Gb/s have been achieved.
Rotating ring fluxon oscillators: Gyroscopic effects
Authors: Marchesoni Fabio
Published: July 2002

We suggest the existence of gyroscopic effects in ring fluxon oscillators, which, due to the extremely narrow oscillation linewidths, could therefore be used as sensitive rotation rate sensors. For the sake of comparison we also improve on previous analytical determinations of the thermal background intensity for oscillating Josephson lines.
Nonlinear nonreciprocity in a coherent mismatched directional coupler
Authors: Trillo S. , Wabnitz S.
Published: July 2002

The analytical solution is given for the nonlinear propagation in a linearly mismatched directional coupler taking into account an arbitrary nonuniform nonlinearity. The effect of mismatching which causes nonreciprocal nonlinear switching of the device is analyzed in detail.
Effect of lattice mismatch in ZnSe epilayers grown on GaAs by molecular beam epitaxy
Authors: Mohammed K. , Cammack D. A. , Dalby R. , Newbury P. , Greenberg B. L. , Petruzzello J. , Bhargava R. N.
Published: July 2002

We report a detailed study of the effect of lattice mismatch on ZnSe epilayers grown on 〈001〉 GaAs by molecular beam epitaxy using photoluminescence (PL), x-ray diffraction, and transmission electron microscopy (TEM) techniques. We find that our samples are of high quality, exhibiting sharp and strong bound excitons, and that these bound excitons shift to higher energies due to tetragonal distortion as the thickness of the ZnSe epilayer is systematically reduced from ∼1 to 0.1 μm. Fairly good agreement is found between PL and x-ray data for the total strain relaxation as a function of layer thickness. TEM measurements are also used to estimate an inelastic component of the strain relaxation in the layers.
Linewidth-narrowed distributed feedback injection lasers with long cavity length and detuned Bragg wavelength
Authors: Liou K.-Y. , Dutta N. K. , Burrus C. A.
Published: July 2002

We report linewidth narrowing for 1.3-μm InGaAsP distributed feedback lasers with either a long cavity length or a detuned Bragg wavelength. The narrowest linewidth measured was 3 MHz at 6 mW for a 780-μm long-cavity laser, and was 8 MHz at 5.5 mW for a 250-μm regular-length laser with detuned wavelength. From our analysis, distributed feedback lasers with 1 MHz linewidth appear to be feasible.
Electric field distribution in the cathode sheath of an electron beam glow discharge
Authors: Lee S. A. , Andersen L.-U. A. , Rocca J. J. , Marconi M. , Reesor N. D.
Published: July 2002

We have measured the electric field distribution in the cathode sheath of an electron beam He glow discharge. Laser saturation spectroscopy was used to determine the quadratic Stark shift produced by the electric field. The experimental results are in good agreement with the calculations of a collisional model of the cathode sheath.
Compositional analysis of the rhodium metal-oxide interface by imaging atom-probe mass spectroscopy
Authors: Kellogg G. L.
Published: July 2002

The chemical composition of a thin rhodium oxide from the surface through the metal-oxide interface has been measured by imaging atom-probe mass spectroscopy. The surface oxide was produced by heating a clean, well-characterized field-emitter surface to 600 K in 1 Torr O2 for 15 min. The oxidized sample was subsequently transferred under ultrahigh vacuum to an imaging atom probe for analysis. To avoid problems associated with a nonuniform oxide layer, only a small volume of the oxide layer was mass analyzed. The results indicated that under these conditions 50–60 layers of stoichiometric Rh2O3 are produced with dissolved oxygen (possibly mixed with substoichiometric oxides) extending an additional 5–15 layers into the bulk. A small amount of H2O was detected within the oxide with an enhanced concentration observed at the interface.
Observation of charge-separating defects in HgCdTe using remote contact electron beam induced current
Authors: Bubulac L. O. , Tennant W. E.
Published: July 2002

A spatially resolved electron beam technique, remote contact electron beam induced current, has been developed to detect and map charge-separating defects in HgCdTe with two remote sample contacts. This technique, characterized by a high spatial resolution, ∼1 μm, and a high sensitivity (signal/noise) to fields produced by inclusions, damage, dislocations, strain, p-n junctions, and possibly compositional (band gap) and doping variations, shows promise for analyzing materials, passivation coatings, and diode arrays without making contacts to the individual devices.
Structure and superconducting properties of Y1Ba2Cu3O7−δ films prepared by transversely excited atmospheric pressure CO2 pulsed laser evaporation
Authors: Miura S. , Yoshitake T. , Satoh T. , Miyasaka Y. , Shohata N.
Published: July 2002

Superconducting Y1Ba2Cu3O7−δ films were prepared by TEA-CO2 pulsed laser evaporation. On SrTiO3(100) the a axis was oriented perpendicular to the substrate surface, while the 〈110〉 axis was oriented perpendicular to the substrate surface on SrTiO3(110). Sharp resistive superconducting transitions with zero resistance at 86 K on SrTiO3(110) and at 83 K on SrTiO3(100) were observed.
Kinetics of structural relaxation and hydrogen evolution from plasma deposited silicon nitride
Authors: Budhani R. C. , Bunshah R. F. , Flinn P. A.
Published: July 2002

Infrared absorption measurements and the temperature dependence of stress have been used to establish the kinetics of structural relaxation and hydrogen evolution from plasma deposited a-SixNy :H films. The Arrhenius rate law describes the dissociation of N–H and Si–H bonds which occurs on annealing the films above 600 °C. The activation energies deduced from the infrared data are lower than the respective bond dissociation energies. The films undergo a rapid stress relaxation in the temperature range 400–650 °C. The discussion of the experimental results highlights possible mechanisms for the evolution of hydrogen from a-SixNy:H networks.
Surface-emitting, multiple quantum well GaAs/AlGaAs laser with wavelength-resonant periodic gain medium
Authors: Raja M. Y. A. , Brueck S. R. J. , Osiński M. , Schaus C. F. , McInerney J. G. , Brennan T. M. , Hammons B. E.
Published: July 2002

A novel surface-emitting semiconductor laser with a vertical resonator, extremely short gain length, and enhanced gain at a specific design wavelength has been demonstrated. The gain medium consists of a series of GaAs quantum wells separated by AlGaAs spacers whose thicknesses are chosen to be one-half the wavelength of a particular transition in the quantum wells. This structure forces the antinodes of the standing-wave optical field to coincide with the gain elements, enhancing the gain and frequency selectivity in the vertical direction and substantially reducing amplified spontaneous emission. We have achieved optically pumped lasing with a threshold of 6 MW/cm2 at room temperature in a molecular beam epitaxially grown structure of thickness 4.3 μm, of which only 320 nm provided gain.
Heteroepitaxial growth of InP on a GaAs substrate by low-pressure metalorganic vapor phase epitaxy
Authors: Horikawa H. , Ogawa Y. , Kawai Y. , Sakuta M.
Published: July 2002

Good quality InP was successfully grown on (100)GaAs 2° off normal toward [011] substrates by introducing low-temperature grown GaAs/InP double buffer layers. It was found that addition of a thin GaAs buffer layer (20 nm thick) grown at low temperature (430 °C) between the GaAs substrate and an InP buffer layer was effective for improving the crystal quality. The full width at half-maximum of the x-ray rocking curve was as narrow as 200 arcsec for a 6-μm-thick InP layer. An electron mobility of 15 000 cm2/(V s) at 77 K was obtained for an unintentionally doped layer. The intensity of the photoluminescence at 77 K was as good as that for an InP substrate.
Growth and transport properties of InAs epilayers on GaAs
Authors: Kalem Seref , Chyi Jen-Inn , Morkoç Hadis , Bean Ross , Zanio Ken
Published: July 2002

A series of InAs epitaxial layers with thicknesses ranging from 0.5 up to 6.2 μm was grown on (100) oriented semi-insulating GaAs substrates by molecular beam epitaxy. The transport properties of the layers have been investigated by Hall effect measurements down to 10 K. The properties of the films are greatly influenced not only by the growth conditions but also by the InAs/GaAs interface structure. The mobility at room temperature is 1.8×104 cm2/V s (n=6.1×1015 cm−3) and peaks at about liquid-nitrogen temperature with a value of 5.173×104 cm2/V s (n=3.1×1015 cm−3) for a 6.2-μm-thick InAs layer. It is shown that the temperature dependence as well as the magnitude of the mobility can be explained by a combined impurity-phonon-dislocation scattering mechanism. From the combination, dislocation densities of the order of 106 cm−2 are found.
Regulatory DNA required for
vnd/NK-2
homeobox gene expression pattern in neuroblasts
Authors: Shao Xiaoping , Koizumi Keita , Nosworthy Neil , Tan Dong-Ping , Odenwald Ward , Nirenberg Marshall
Published: July 2002

Vnd/NK-2 protein was detected in 11 neuroblasts per hemisegment
in
Drosophila
embryos, 9 medial and 2 intermediate
neuroblasts. Fragments of DNA from the 5′-flanking region of the
vnd
/
NK-2
gene were inserted upstream of
an enhancerless
βgalactosidase
gene in a
P-element and used to generate transgenic fly lines. Antibodies
directed against Vnd/NK-2 and β-galactosidase proteins then were
used in double-label experiments to correlate the expression of
β-galactosidase and Vnd/NK-2 proteins in identified neuroblasts.
DNA region A, which corresponds to the −4.0 to −2.8-kb fragment of
DNA from the 5′-flanking region of the
vnd
/
NK-2
gene was shown to contain one
or more strong enhancers required for expression of the
vnd
/
NK-2
gene in ten neuroblasts. DNA
region B (−5.3 to −4.0 kb) contains moderately strong enhancers for
vnd
/
NK-2
gene expression in four
neuroblasts. Hypothesized DNA region C, whose location was not
identified, contains one or more enhancers that activate
vnd
/
NK-2
gene expression only in one
neuroblast. These results show that nucleotide sequences in at least
three regions of DNA regulate the expression of the
vnd
/
NK-2
gene, that the
vnd
/
NK-2
gene can be activated in
different ways in different neuroblasts, and that the pattern of
vnd
/
NK-2
gene expression in neuroblasts
of the ventral nerve cord is the sum of partial patterns.
Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status
Authors: Mao Yinghui , Mehl Issac R. , Muller Mark T.
Published: July 2002

The nonconserved, hydrophilic N-terminal domain of eukaryotic DNA topoisomerase I (topo I) is dispensable for catalytic activity
in vitro
but essential
in vivo
. There are at least five putative nuclear localization signals and a nucleolin-binding signal within the first 215 residues of the topo I N-terminal domain. We have investigated physiological functions of the topo I N-terminal domain by fusing it to an enhanced green fluorescent protein (EGFP). The first 170 residues of the N-terminal domain allow efficient import of chimeric proteins into nuclei and nucleoli. The nucleolar localization of this protein does not depend on its interaction with nucleolin, whereas ongoing rDNA transcription clearly is crucial. Immunoprecipitation experiments reveal that the topo I N terminus (topoIN)-EGFP fusion protein associates with the TATA-binding protein in cells. Furthermore, DNA damage results in extensive nuclear redistribution of the topoIN-EGFP chimeric product. The redistribution is also p53-dependent and the N terminus of topo I appears to interact with p53
in vivo
. These results show that the topo I localization to the nucleolus is related to the p53 and DNA damage, as well as changes in transcriptional status. Nucleolar release of topo I under conditions of cellular duress may represent an important, antecedent step in tumor cell killing by topoisomerase active agents.
Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α
Authors: Kline David D. , Peng Ying-Jie , Manalo Dominador J. , Semenza Gregg L. , Prabhakar Nanduri R.
Published: July 2002

To investigate whether the transcriptional activator hypoxia-inducible factor 1 (HIF-1) is required for ventilatory responses to hypoxia, we analyzed mice that were either wild type or heterozygous for a loss-of-function (knockout) allele at the
Hif1a
locus, which encodes the O
2
-regulated HIF-1α subunit. Although the ventilatory response to acute hypoxia was not impaired in
Hif1a

+/−

mice, the response was primarily mediated via vagal afferents, whereas in wild-type mice, carotid body chemoreceptors played a predominant role. When carotid bodies isolated from wild-type mice were exposed to either cyanide or hypoxia, a marked increase in sinus nerve activity was recorded, whereas carotid bodies from
Hif1a

+/−

mice responded to cyanide but not to hypoxia. Histologic analysis revealed no abnormalities of carotid body morphology in
Hif1a

+/−

mice. Wild-type mice exposed to hypoxia for 3 days manifested an augmented ventilatory response to a subsequent acute hypoxic challenge. In contrast, prior chronic hypoxia resulted in a diminished ventilatory response to acute hypoxia in
Hif1a

+/−

mice. Thus partial HIF-1α deficiency has a dramatic effect on carotid body neural activity and ventilatory adaptation to chronic hypoxia.
Centrosome amplification drives chromosomal instability in breast tumor development
Authors: Lingle Wilma L. , Barrett Susan L. , Negron Vivian C. , D'Assoro Antonino B. , Boeneman Kelly , Liu Wanguo , Whitehead Clark M. , Reynolds Carol , Salisbury Jeffrey L.
Published: July 2002

Earlier studies of invasive breast tumors have shown that 60–80% are aneuploid and ≈80% exhibit amplified centrosomes. In this study, we investigated the relationship of centrosome amplification with aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human breast tumors. Twenty invasive breast tumors and seven normal breast tissues were analyzed by fluorescence
in situ
hybridization with centromeric probes to chromosomes 3, 7, and 17. We analyzed these tumors for both aneuploidy and unstable karyotypes as determined by chromosomal instability. The results were then tested for correlation with three measures of centrosome amplification: centrosome size, centrosome number, and centrosome microtubule nucleation capacity. Centrosome size and centrosome number both showed a positive, significant, linear correlation with aneuploidy and chromosomal instability. Microtubule nucleation capacity showed no such correlation, but did correlate significantly with loss of tissue differentiation. Centrosome amplification was detected in
in situ
ductal carcinomas, suggesting that centrosome amplification is an early event in these lesions. Centrosome amplification and chromosomal instability occurred independently of p53 mutation, whereas p53 mutation was associated with a significant increase in centrosome microtubule nucleation capacity. Together, these results demonstrate that independent aspects of centrosome amplification correlate with chromosomal instability and loss of tissue differentiation and may be involved in tumor development and progression. These results further suggest that aspects of centrosome amplification may have clinical diagnostic and/or prognostic value and that the centrosome may be a potential target for cancer therapy.
The origin of the eukaryotic cell: A genomic investigation
Authors: Hartman Hyman , Fedorov Alexei
Published: July 2002

We have collected a set of 347 proteins that are found in eukaryotic cells but have no significant homology to proteins in Archaea and Bacteria. We call these proteins eukaryotic signature proteins (ESPs). The dominant hypothesis for the formation of the eukaryotic cell is that it is a fusion of an archaeon with a bacterium. If this hypothesis is accepted then the three cellular domains, Eukarya, Archaea, and Bacteria, would collapse into two cellular domains. We have used the existence of this set of ESPs to test this hypothesis. The evidence of the ESPs implicates a third cell (chronocyte) in the formation of the eukaryotic cell. The chronocyte had a cytoskeleton that enabled it to engulf prokaryotic cells and a complex internal membrane system where lipids and proteins were synthesized. It also had a complex internal signaling system involving calcium ions, calmodulin, inositol phosphates, ubiquitin, cyclin, and GTP-binding proteins. The nucleus was formed when a number of archaea and bacteria were engulfed by a chronocyte. This formation of the nucleus would restore the three cellular domains as the Chronocyte was not a cell that belonged to the Archaea or to the Bacteria.
Intracellular distribution of viral gene products regulates a complex mechanism of cauliflower mosaic virus acquisition by its aphid vector
Authors: Drucker Martin , Froissart Rémy , Hébrard Eugénie , Uzest Marilyne , Ravallec Marc , Espérandieu Pascal , Mani Jean-Claude , Pugnière Martine , Roquet Françoise , Fereres Alberto , Blanc Stéphane
Published: July 2002

Interactions between
Cauliflower mosaic virus
(CaMV) and its aphid vector are regulated by the viral protein P2, which binds to the aphid stylets, and protein P3, which bridges P2 and virions. By using baculovirus expression of P2 and P3, electron microscopy, surface plasmon resonance, affinity chromatography, and transmission assays, we demonstrate that P3 must be previously bound to virions in order that attachment to P2 will allow aphid transmission of CaMV. We also show that a P2:P3 complex exists in the absence of virions but is nonfunctional in transmission. Hence, unlike P2, P3 and virions cannot be sequentially acquired by the vector. Immunogold labeling revealed the predominance of spatially separated P2:P3 and P3:virion complexes in infected plant cells. This specific distribution indicates that the transmissible complex, P2:P3:virion, does not form primarily in infected plants but in aphids. A model, describing the regulating role of P3 in the formation of the transmissible CaMV complex
in planta
and during acquisition by aphids, is presented, and its consequences are discussed.
Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid β-peptide of amyloid plaques
Authors: Perutz M. F. , Pope B. J. , Owen D. , Wanker E. E. , Scherzinger E.
Published: July 2002

The exon-1 peptide of huntingtin has 51 Gln repeats and produces the symptoms of Huntington's disease in transgenic mice. Aggregation of the yeast Sup35 protein into prions has been attributed to its glutamine-rich and asparagine-rich domain. Here, we show that poly-
l
-asparagine forms polar zippers similar to those of poly-
l
-glutamine. In solution at acid pH, the glutamine-rich and asparagine-rich 18-residue Sup35 peptide, rendered soluble by the addition of two aspartates at the amino end and two lysines at the carboxyl end, gives a β-sheet CD spectrum; it aggregates at neutral pH. A poly-alanine peptide D
2
A
10
K
2
gives an α-helical CD spectrum at all pHs and does not aggregate; a peptide with the sequence of the C-terminal helix of the α-chain of human hemoglobin, preceded by two aspartates and followed by two lysines, exhibits a random coil spectrum and does not aggregate either. Alignment of several β-strands with the sequence of the 42-residue Alzheimer's amyloid β-peptide shows that they can be linked together by a network of salt bridges. We also asked why single amino acid replacements can so destabilize the native structures of proteins that they unfold and form amyloids. The difference in free energy of a protein molecule between its native, fully ordered structure and an amorphous mixture of randomly coiled chains is only of the order of 10 kcal/mol. Theory shows that destabilization of the native structure by no more than 2 kcal/mol can increase the probability of nucleation of disordered aggregates from which amyloids could grow 130,000-fold.
Posttranscriptional regulation of Bruton's tyrosine kinase expression in antigen receptor-stimulated splenic B cells
Authors: Nisitani Sazuku , Satterthwaite Anne B. , Akashi Koichi , Weissman Irving L. , Witte Owen N. , Wahl Matthew I.
Published: July 2002

Mutation of Bruton's tyrosine kinase (Btk) causes human X-linked agammaglobulinemia and murine X-linked immunodeficiency syndrome (xid). Quantitative aspects of B lymphocyte development and function have been demonstrated to depend on Btk levelin vivoby using a murine transgenic model system. A sensitive intracellular immunofluorescent assay was developed to measure Btk protein on a per cell basis to test the hypothesis that its dosage is dynamically regulated during B cell development or functional responses. Marrow-derived hematopoietic stem cells, common lymphoid progenitor cells, and developing B and myeloid lineages expressed Btk protein at comparable levels. Resting peripheral B lineage cells had a significantly lower amount of Btk than marrow-derived cells in both wild-type and xid mice. Activation of the B cell antigen receptor up-regulated Btk protein level 10-fold within several hours by a phosphatidylinositol 3-kinase-dependent, posttranscriptional mechanism. In contrast, the protein level of Btk R28C in activated B lymphocytes from xid mice remained low. Bypass of the antigen receptor signaling pathways by treatment of cells with phorbol myristic acid and ionomycin rescued up-regulation of Btk protein in xid splenic B cells. These combined results suggest that certain receptor signals mediated by Btk regulate the level of expression of Btk protein in responding B lymphocytes to potentiate signal transduction. Dynamic regulation of Btk protein dosage is an additional mechanism to modulate B lymphocyte immune functions.
Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite
Toxoplasma gondii
Authors: Jelenska J. , Crawford M. J. , Harb O. S. , Zuther E. , Haselkorn R. , Roos D. S. , Gornicki P.
Published: July 2002

Apicomplexan parasites such as
Toxoplasma gondii
contain a primitive plastid, the apicoplast, whose genome consists of a
35-kb circular DNA related to the plastid DNA of plants. Plants
synthesize fatty acids in their plastids. The first committed step in
fatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACC). This
enzyme is encoded in the nucleus, synthesized in the cytosol, and
transported into the plastid. In the present work, two genes encoding
ACC from
T. gondii
were cloned and the gene structure
was determined. Both ORFs encode multidomain proteins, each with an
N-terminal extension, compared with the cytosolic ACCs from plants. The
N-terminal extension of one isozyme, ACC1, was shown to target green
fluorescent protein to the apicoplast of
T. gondii
. In
addition, the apicoplast contains a biotinylated protein,
consistent with the assertion that ACC1 is localized there. The second
ACC in
T. gondii
appears to be cytosolic.
T.
gondii
mitochondria also contain a biotinylated
protein, probably pyruvate carboxylase. These results confirm the
essential nature of the apicoplast and explain the inhibition of
parasite growth in cultured cells by herbicides targeting ACC.
FRS2α attenuates FGF receptor signaling by Grb2- mediated recruitment of the ubiquitin ligase Cbl
Authors: Wong Andy , Lamothe Betty , Lee Arnold , Schlessinger Joseph , Lax Irit
Published: July 2002

Attenuation of growth factor signaling is essential for the regulation of developmental processes and tissue homeostasis in most organisms. The product of Cbl protooncogene is one such regulator, which functions as an ubiquitin ligase that ubiquitinates and promotes the degradation of a variety of cell signaling proteins. Here, we demonstrate that Grb2 bound to tyrosine-phosphorylated FRS2α forms a ternary complex with Cbl by means of its Src homology 3 domains resulting in the ubiquitination of fibroblast growth factor (FGF) receptor and FRS2α in response to FGF stimulation. These observations highlight the importance of FRS2α in the assembly of both positive (i.e., Sos, phosphatidylinositol 3-kinase) and negative (i.e., Cbl) signaling proteins to mediate a balanced FGF signal transduction. However, the partial inhibition of FGF receptor down-regulation in FRS2α−/− cells indicates that the attenuation of signaling by FGF receptor is regulated by redundant or multiple mechanisms.
Mot1 activates and represses transcription by direct, ATPase-dependent mechanisms
Authors: Dasgupta Arindam , Darst Russell P. , Martin Karla J. , Afshari Cynthia A. , Auble David T.
Published: July 2002

Mot1 is an essential yeast Snf2/Swi2-related ATPase that exerts both positive and negative effects on gene expression.
In vitro
, Mot1 can disrupt TATA-binding protein–DNA complexes in an ATP-dependent reaction. This activity can explain Mot1-mediated transcriptional repression, but how Mot1 activates transcription is unknown. We demonstrate that, remarkably, Mot1 is localized
in vivo
to promoters for both Mot1-repressed and Mot1-activated genes. Moreover, Mot1 ATPase activity is required for both activation and repression of gene activity. These findings suggest a novel function for the Mot1 ATPase at activated genes, perhaps involving ATP-driven reorganization of the preinitiation complex. Mot1 regulates the expression of ≈3% of yeast genes in cells grown in rich medium. Most of these genes are repressed by Mot1, consistent with Mot1's ATP-dependent TATA-binding protein–DNA dissociating activity. Additionally, ≈77% of the Mot1-repressed genes are involved in the diauxic shift, stress response, mating, or sporulation. The gene sets controlled by NC2 and Srb10 are strongly correlated with the Mot1-controlled set, suggesting that these factors cooperate in transcriptional control on a global scale.
Hydrogen peroxide homeostasis: Activation of plant catalase by calcium/calmodulin
Authors: Yang T. , Poovaiah B. W.
Published: July 2002

Environmental stimuli such as UV, pathogen attack, and gravity can induce rapid changes in hydrogen peroxide (H
2
O
2
) levels, leading to a variety of physiological responses in plants. Catalase, which is involved in the degradation of H
2
O
2
into water and oxygen, is the major H
2
O
2
-scavenging enzyme in all aerobic organisms. A close interaction exists between intracellular H
2
O
2
and cytosolic calcium in response to biotic and abiotic stresses. Studies indicate that an increase in cytosolic calcium boosts the generation of H
2
O
2
. Here we report that calmodulin (CaM), a ubiquitous calcium-binding protein, binds to and activates some plant catalases in the presence of calcium, but calcium/CaM does not have any effect on bacterial, fungal, bovine, or human catalase. These results document that calcium/CaM can down-regulate H
2
O
2
levels in plants by stimulating the catalytic activity of plant catalase. Furthermore, these results provide evidence indicating that calcium has dual functions in regulating H
2
O
2
homeostasis, which in turn influences redox signaling in response to environmental signals in plants.
Ex vivo
cell labeling with
64
Cu–pyruvaldehyde-bis(
N
4
-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography
Authors: Adonai Nora , Nguyen Khoi N. , Walsh Joseph , Iyer M. , Toyokuni Tatsushi , Phelps Michael E. , McCarthy Timothy , McCarthy Deborah W. , Gambhir Sanjiv Sam
Published: July 2002

We have used copper-64-pyruvaldehyde-bis(
N
4
-methylthiosemicarbazone) (
64
Cu–PTSM) to radiolabel cells
ex vivo
for
in vivo
positron-emission tomography (PET) imaging studies of cell trafficking in mice and for eventual application in patients. 2-[
18
F]-Fluoro-2-deoxy-
d
-glucose (FDG) cell labeling also was evaluated for comparison.
64
Cu–PTSM uptake by C6 rat glioma (C6) cells increased for 180 min and then stabilized. The labeling efficiency was directly proportional to
64
Cu–PTSM concentration and influenced negatively by serum. Label uptake per cell was greater with
64
Cu–PTSM than with FDG. However, both
64
Cu–PTSM- and FDG-labeled cells showed efflux of cell activity into supernatant. The
64
Cu–PTSM labeling procedure did not interfere significantly with C6 cell viability and proliferation rate. MicroPET images of living mice indicate that tail-vein-injected labeled C6 cells traffic to the lungs and liver. In addition, transient splenic accumulation of radioactivity was clearly detectable in a mouse scanned at 3.33 h postinfusion of
64
Cu–PTSM-labeled lymphocytes. In contrast, the liver was the principal organ of tracer localization after tail-vein administration of
64
Cu–PTSM alone. These results indicate that
in vivo
imaging of cell trafficking is possible with
64
Cu–PTSM-labeled cells. Given the longer
t
1/2
of
64
Cu (12.7 h) relative to
18
F (110 min), longer cell-tracking periods (up to 24–36 h) should be possible now with PET.
Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme
Authors: Nelson Daniel , Loomis Lawrence , Fischetti Vincent A.
Published: July 2002

Bacteriophage lytic enzymes quickly destroy the cell wall of the host bacterium to release progeny phage. Because such lytic enzymes specifically kill the species in which they were produced, they may represent an effective way to control pathogenic bacteria without disturbing normal microflora. In this report, we studied a murein hydrolase from the streptococcal bacteriophage C1termed lysin. This enzyme is specific for groups A, C, and E streptococci, with little or no activity toward several oral streptococci or other commensal organisms tested. Using purified lysinin vitro, we show that 1,000 units (10 ng) of enzyme is sufficient to sterilize a culture of ≈107group A streptococci within 5 seconds. When a single dose of lysin (250 units) is first added to the oral cavity of mice, followed by 107live group A streptococci, it provides protection from colonization (28.5% infected,n= 21) compared with controls without lysin (70.5% infected,n= 17) (P< 0.03). Furthermore, when lysin (500 units) was given orally to 9 heavily colonized mice, no detectable streptococci were observed 2 h after lysin treatment. In all, these studies show that lysin represents a unique murein hydrolase that has a rapid lethal effect bothin vitroandin vivoon group A streptococci, without affecting other indigenous microorganisms analyzed. This general approach may be used to either eliminate or reduce streptococci from the upper respiratory mucosal epithelium of either carriers or infected individuals, thus reducing associated disease.
Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis
Authors: Borsig Lubor , Wong Richard , Feramisco James , Nadeau David R. , Varki Nissi M. , Varki Ajit
Published: July 2002

Independent studies indicate that expression of sialylated fucosylated mucins by human carcinomas portends a poor prognosis because of enhanced metastatic spread of tumor cells, that carcinoma metastasis in mice is facilitated by formation of tumor cell complexes with blood platelets, and that metastasis can be attenuated by a background of P-selectin deficiency or by treatment with heparin. The effects of heparin are not primarily due to its anticoagulant action. Other explanations have been suggested but not proven. Here, we bring together all these unexplained and seemingly disparate observations, showing that heparin treatment attenuates tumor metastasis in mice by inhibiting P-selectin-mediated interactions of platelets with carcinoma cell-surface mucin ligands. Selective removal of tumor mucin P-selectin ligands, a single heparin dose, or a background of P-selectin deficiency each reduces tumor cell-platelet interactionsin vitroandin vivo. Although each of these maneuvers reduced thein vivointeractions for only a few hours, all markedly reduce long-term organ colonization by tumor cells. Three-dimensional reconstructions by using volume-rendering software show that each situation interferes with formation of the platelet “cloak” around tumor cells while permitting an increased interaction of monocytes (macrophage precursors) with the malignant cells. Finally, we show that human P-selectin is even more sensitive to heparin than mouse P-selectin, giving significant inhibition at concentrations that are in the clinically acceptable range. We suggest that heparin therapy for metastasis prevention in humans be revisited, with these mechanistic paradigms in mind.
Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging
Authors: Seeman Teresa E. , McEwen Bruce S. , Rowe John W. , Singer Burton H.
Published: July 2002

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70–79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.
IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase
Authors: Li Shyun , Strelow Astrid , Fontana Elizabeth J. , Wesche Holger
Published: July 2002

Toll/IL-1 receptor family members are central components of host defense mechanisms in a variety of species. One well conserved element in their signal transduction is Ser/Thr kinases, which couple early signaling events in a receptor complex at the plasma membrane to larger signalosomes in the cytosol. The fruit flyDrosophila melanogasterhas one member of this family of kinases, termed Pelle. The complexity of this pathway is vastly increased in vertebrates, and several Pelle homologs have been described and termed IL-1 receptor-associated kinase (IRAK). Here we report the identification of a novel and distinct member of the IRAK family, IRAK-4. IRAK-4 is the closest human homolog to Pelle. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent manner, and overexpression of IRAK-4 can activate NF-κB as well as mitogen-activated protein (MAP) kinase pathways. Most strikingly, and in contrast to the other IRAKs, IRAK-4 depends on its kinase activity to activate NF-κB. In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1.
T-bet regulates IgG class switching and pathogenic autoantibody production
Authors: Peng Stanford L. , Szabo Susanne J. , Glimcher Laurie H.
Published: July 2002

A molecular understanding of the regulation of IgG class switching to IL-4-independent isotypes, particularly to IgG2a, remains largely unknown. The T-box transcription factor T-bet directly regulates Th1 lineage commitment by CD4 T cells, but its role in B lymphocytes has been largely unexplored. We show here a role for T-bet in the regulation of IgG class switching, especially to IgG2a. T-bet-deficient B lymphocytes demonstrate impaired production of IgG2a, IgG2b, and IgG3 and, most strikingly, are unable to generate germ-line or postswitch IgG2a transcripts in response to IFN-γ. Conversely, enforced expression of T-bet initiates IgG2a switching in cell lines and primary cells. This function contributes critically to the pathogenesis of murine lupus, where the absence of T-bet strikingly reduces B cell-dependent manifestations, including autoantibody production, hypergammaglobulinemia, and immune-complex renal disease and, in particular, abrogates IFN-γ-mediated IgG2a production. Classical T cell manifestations persisted, including lymphadenopathy and cellular infiltrates of skin and liver. These results identify T-bet as a selective transducer of IFN-γ-mediated IgG2a class switching in B cells and emphasize the importance of this regulation in the pathogenesis of humorally mediated autoimmunity.
Phosphorylation of protein kinase N by phosphoinositide-dependent protein kinase-1 mediates insulin signals to the actin cytoskeleton
Authors: Dong Lily Q. , Landa Luis R. , Wick Michael J. , Zhu Li , Mukai Hideyuki , Ono Yoshitaka , Liu Feng
Published: July 2002

Growth factors such as insulin regulate phosphatidylinositol 3-kinase-dependent actin cytoskeleton rearrangement in many types of cells. However, the mechanism by which the insulin signal is transmitted to the actin cytoskeleton remains largely unknown. Yeast two-hybrid screening revealed that the phosphatidylinositol 3-kinase downstream effector phosphoinositide-dependent protein kinase-1 (PDK1) interacted with protein kinase N (PKN), a Rho-binding Ser/Thr protein kinase potentially implicated in a variety of cellular events, including phosphorylation of cytoskeletal components. PDK1 and PKN interacted
in vitro
and in intact cells, and this interaction was mediated by the kinase domain of PDK1 and the carboxyl terminus of PKN. In addition to a direct interaction, PDK1 also phosphorylated Thr
774
in the activation loop and activated PKN. Insulin treatment or ectopic expression of the wild-type PDK1 or PKN, but not protein kinase Cζ, induced actin cytoskeleton reorganization and membrane ruffling in 3T3-L1 fibroblasts and Rat1 cells that stably express the insulin receptor (Rat1-IR). However, the insulin-stimulated actin cytoskeleton reorganization in Rat1-IR cells was prevented by expression of kinase-defective PDK1 or PDK1-phosphorylation site-mutated PKN. Thus, phosphorylation by PDK1 appears to be necessary for PKN to transduce signals from the insulin receptor to the actin cytoskeleton.
Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and
N
-methyl-
d
-aspartate receptor subunits gene transcripts in male rats
Authors: Le Grevès Madeleine , Steensland Pia , Le Grevès Pierre , Nyberg Fred
Published: July 2002

Studies were conducted to evaluate the effects of s.c. injected recombinant human growth hormone (GH) on the expression of the gene transcript of
N
-methyl-D-aspartate receptor subunits type 1 (NR1), type 2A (NR2A), and type 2B (NR2B) in the male rat hippocampus. The GH-induced effects on the expression of hippocampal gene transcripts of GH receptor (GHR) and GH-binding protein were also examined. Male Sprague–Dawley rats, kept in four groups of two different ages, was treated with the hormone or saline during 10 days before decapitation and tissue dissection. Brain tissues collected were analyzed for mRNA content by using the Northern blot technique. The results indicated that in adult young rats (11 weeks of age) the hormone elicited a decrease in the mRNA expression of NR1 but an increase in that of the NR2B subunit. In elderly adult rats (57–67 weeks of age) GH induced an increase in the expression of the hippocampal message for NR1 and NR2A. Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats. It was further found that a significant positive correlation exists between the level of GHR mRNA and the expression of the NR2B subunit transcript in adult young rats. The GH-induced increase in the expression of hippocampal mRNA for the NR2B subunit is compatible with a previously observed memory promoting effect seen for the hormone, because overexpression of this
N
-methyl-D-aspartate receptor subunit is shown to enhance cognitive capabilities.
Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains ofHelicobacter pyloriand prevents benzo[a]pyrene-induced stomach tumors
Authors: Fahey Jed W. , Haristoy Xavier , Dolan Patrick M. , Kensler Thomas W. , Scholtus Isabelle , Stephenson Katherine K. , Talalay Paul , Lozniewski Alain
Published: July 2002

Gastric infection withHelicobacter pyloriis a cosmopolitan problem, and is especially common in developing regions where there is also a high prevalence of gastric cancer. These infections are known to cause gastritis and peptic ulcers, and dramatically enhance the risk of gastric cancer. Eradication of this organism is an important medical goal that is complicated by the development of resistance to conventional antimicrobial agents and by the persistence of a low level reservoir ofH. pyloriwithin gastric epithelial cells. Moreover, economic and practical problems preclude widespread and intensive use of antibiotics in most developing regions. We have found that sulforaphane [(−)-1-isothiocyanato-(4R)-(methylsulfinyl)butane], an isothiocyanate abundant as its glucosinolate precursor in certain varieties of broccoli and broccoli sprouts, is a potent bacteriostatic agent against 3 reference strains and 45 clinical isolates ofH. pylori[minimal inhibitory concentration (MIC) for 90% of the strains is ≤4 μg/ml], irrespective of their resistance to conventional antibiotics. Further, brief exposure to sulforaphane was bactericidal, and eliminated intracellularH. pylorifrom a human epithelial cell line (HEp-2). In complementary experiments, sulforaphane blocked benzo[a]pyrene-evoked forestomach tumors in ICR mice. This protection resulted from induction of phase 2 detoxication and antioxidant enzymes, and was abrogated in mice lacking thenrf2gene, which regulates phase 2 enzymes. Thus, the dual actions of sulforaphane in inhibitingHelicobacterinfections and blocking gastric tumor formation offer hope that these mechanisms might function synergistically to provide diet-based protection against gastric cancer in humans.