bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystalline reconstruction in Ni–Cr–Fe/Ni–Fe films
Authors: Lin Tsann , Mauri Daniele , York Brian , Rice Philip M.
Published: January 2004

It is found in this study that crystalline reconstruction occurs when a nonmagnetic Ni–Cr–Fe film and a ferromagnetic Ni–Fe film are sequentially deposited, but does not occur when the deposition sequence is reversed. This unexpected phenomenon causes the Ni–Cr–Fe/Ni–Fe films to behave more like a monolayer film that exhibits lower electrical resistance, stronger 〈111〉 texture, and larger polycrystalline grains than Ni–Fe/Ni–Cr–Fe films. This crystalline reconstruction causes an anisotropy magnetoresistance (AMR) sensor to exhibit a high AMR coefficient, and also causes a giant magnetoresistance (GMR) sensor to exhibit a high GMR coefficient. By controlling this crystalline reconstruction, GMR properties can be optimized for the proper operation of the GMR sensor.
Spin-dependent transport in lateral periodic magnetic modulations: Scheme for spin filters
Authors: Zhou J. , Shi Q. W. , Wu M. W.
Published: January 2004

A scheme for spin filters is proposed by studying the coherent transport of electrons through quantum wires with lateral magnetic modulation. Unlike other schemes reported in the literature, the modulation in our scheme is much weaker than the Fermi energy. Large spin polarization through the filter is predicted. Further study suggests the robustness of this spin filter.
Buffer-layer-induced barrier reduction: Role of tunneling in organic light-emitting devices
Authors: Zhang S. T. , Ding X. M. , Zhao J. M. , Shi H. Z. , He J. , Xiong Z. H. , Ding H. J. , Obbard E. G. , Zhan Y. Q. , Huang W. , Hou X. Y.
Published: January 2004

Based on the WKB approximation of the tunneling model, we calculate the J–V characteristics of organic light-emitting devices (OLEDs) having buffer layers of different thickness. The results show how the insertion of a buffer layer with proper thickness lowers the OLED turn-on voltage. Further calculation suggests some parameters, such as the resistivity ratio and the position of the conduction band minimum of the buffer layer relative to the lowest unoccupied molecular orbital of the organic layer, are important in selecting a buffer material. A quantitative estimation of the optimal buffer layer thickness is also presented to serve as a guide to device design. The model is validated by comparison of its predictions to experimental results.
Controlled inflation of voids in cellular polymer ferroelectrets: Optimizing electromechanical transducer properties
Authors: Wegener M. , Wirges W. , Gerhard-Multhaupt R. , Dansachmüller M. , Schwödiauer R. , Bauer-Gogonea S. , Bauer S. , Paajanen M. , Minkkinen H. , Raukola J.
Published: January 2004

When exposed to sufficiently high electric fields, polymer-foam electret materials with closed cells exhibit ferroelectric-like behavior and may therefore be called ferroelectrets. In cellular ferroelectrets, the influence of the cell size and shape distributions on the application-relevant properties is not yet understood. Therefore, controlled inflation experiments were carried out on cellular polypropylene films, and the resulting elastical and electromechanical parameters were determined. The elastic modulus in the thickness direction shows a minimum with a corresponding maximum in the electromechanical transducer coefficient. The resonance frequency shifts as a function of the elastic modulus and the relative density of the inflated cellular films. Therefore, the transducer properties of cellular ferroelectrets can be optimized by means of controlled inflation.
Carrier lifetime in conductive and vanadium-doped 6H-SiC substrates
Authors: Tamulaitis G. , Yilmaz I. , Shur M. S. , Anderson T. , Gaska R.
Published: January 2004

Conductive undoped and semi-insulating vanadium-doped 6H-SiC substrates were studied using the light-induced transient grating technique and photoluminescence (PL) spectroscopy. Carrier lifetime of 400±10 ps and diffusion coefficient of 2.7±0.2 cm2 s−1 were obtained for the nominally undoped wafer, while the corresponding parameters for the V-doped wafer were estimated to be 130±5 ps and 0.9±0.5 cm2 s−1, respectively. The peak PL intensity in the vanadium-doped wafers is more than three orders of magnitude lower than that in nominally undoped wafers. Low-temperature cw PL spectra revealed a band peaked at 507 nm, which is caused by V doping.
High-temperature, high-power, continuous-wave operation of buried heterostructure quantum-cascade lasers
Authors: Evans A. , Yu J. S. , David J. , Doris L. , Mi K. , Slivken S. , Razeghi M.
Published: January 2004

We report cw operation of buried heterostructure quantum-cascade lasers (λ=6 μm) using a thick electroplated Au top contact layer and epilayer-up bonding on a copper heat sink up to a temperature of 333 K (60 °C). The high cw optical output powers of 446 mW at 293 K, 372 mW at 298 K, and 30 mW at 333 K are achieved with threshold current densities of 2.19, 2.35, and 4.29 kA/cm2 respectively, for a high-reflectivity-coated, 9-μm-wide and 3-mm-long laser.
Gold nanowires from silicon nanowire templates
Authors: Wong T. C. , Li C. P. , Zhang R. Q. , Lee S. T.
Published: January 2004

We report a simple method for producing gold nanowires (AuNWs) by using silicon nanowires (SiNWs) as templates. Uniform AuNWs were formed in the core of SiNWs, when SiNWs coated with Au were furnace annealed at ∼880 °C at 10−2 Torr. Transmission electron microscopy (TEM) examination showed the AuNWs had diameters of ∼10 nm. High-resolution TEM revealed lattice fringes with an interlayer spacing of 0.235 nm, which corresponds to the spacing in Au crystal, confirming the AuNWs are crystalline.
Self-assembly of one-dimensional molecular nanostructures on the Ge-covered Si(100) surface
Authors: Zhang Y. P. , Yang L. , Lai Y. H. , Xu G. Q. , Wang X. S.
Published: January 2004

The formation of self-assembled one-dimensional molecular nanostructures on Si(100) is studied by scanning tunneling microscopy. Using the Ge-covered Si(100)-2×n surface as a tempting template, we have obtained large-scale one-dimensional styrene molecular nanostructures. The styrene molecules selectively bond to the Ge/Si(100)-2×n surface through the interactions between one C=C bond of the vinyl group and a Ge=Ge dimer to form C–Ge linkages via a [2+2] cycloaddition. This result may provide a pathway for forming controlled organic nanostructures on the Si(100) surfaces.
Enhanced luminescence of Gd2O3:Eu3+ thin-film phosphors by Li doping
Authors: Yi Soung-soo , Bae Jong Seong , Shim Kyoo Sung , Jeong Jung Hyun , Park Jung-Chul , Holloway P. H.
Published: January 2004

Gd 2 O 3 : Eu 3+ and Li-doped Gd2O3:Eu3+ luminescent thin films have been grown on Al2O3 (0001) substrates using pulsed-laser deposition. The films grown under different deposition conditions show different microstructural and luminescent characteristics. Both cubic and monoclinic crystalline structures were observed in Gd2O3:Eu3+ films, but only the cubic crystalline structure was observed for Li-doped Gd2O3:Eu3+ films grown under certain condition. The photoluminescence (PL) brightness data obtained from Li-doped Gd2O3:Eu3+ films indicate that sapphire is a promising substrate for growth of high-quality Li-doped Gd2O3:Eu3+ thin-film red phosphor. In particular, incorporation of Li+ ions into the Gd2O3 lattice can induce a remarkable increase of PL. The highest emission intensity was observed with LiF-doped Gd1.84Li0.08Eu0.08O3, whose brightness was a factor of 2.3 larger than that from Gd2O3:Eu3+ films. This phosphor is promising for applications in flat-panel displays.
Depletion-mode InGaAs metal-oxide-semiconductor field-effect transistor with oxide gate dielectric grown by atomic-layer deposition
Authors: Ye P. D. , Wilk G. D. , Yang B. , Kwo J. , Gossmann H.-J. L. , Hong M. , Ng K. K. , Bude J.
Published: January 2004

Recently, significant progress has been made on GaAs metal-oxide-semiconductor field-effect transistors (MOSFETs) using atomic-layer deposition (ALD)-grown Al2O3 as gate dielectric. We show here that further improvement can be achieved by inserting a thin In0.2Ga0.8As layer as part of the channel between Al2O3 and GaAs channel. A 1-μm-gate-length, depletion-mode, n-channel In0.2Ga0.8As/GaAs MOSFET with an Al2O3 gate oxide of 160 Å shows a gate leakage current density less than 10−4 A/cm2, a maximum transconductance ∼105 mS/mm, and a strong accumulation current at Vgs>0 in addition to buried-channel conduction. Together with longer gate-length devices, we deduce electron accumulation surface mobility for In0.2Ga0.8As as high as 660 cm2/V s at Al2O3/In0.2Ga0.8As interface.
Photovoltaic effect of lead lanthanum zirconate titanate in a layered film structure design
Authors: Ichiki M. , Maeda R. , Morikawa Y. , Mabune Y. , Nakada T. , Nonaka K.
Published: January 2004

This letter reports on the formation of a layered film structure and the highly improved photovoltaic output of the lead lanthanum zirconate titanate (PLZT) employed. The photovoltaic current of the PLZT film per unit width was more than 102 times larger than that of bulk PLZT, while the photovoltaic voltage per unit thickness in the layered film structure was almost the same as that in bulk ceramics. These differences are due to the characteristics of the film structure and configuration of the electrode. A simple model is used for the phenomenological explanation of the improved photovoltaic effect of the PLZT film.
Comparison of stability of WSiX/SiC and Ni/SiC Schottky rectifiers to high dose gamma-ray irradiation
Authors: Kim Jihyun , Ren F. , Chung G. Y. , MacMillan M. F. , Baca A. G. , Briggs R. D. , Schoenfeld D. , Pearton S. J.
Published: January 2004

SiC Schottky rectifiers with moderate breakdown voltages of ∼450 V and with either WSiX or Ni rectifying contacts were irradiated with Co-60 γ-rays to doses up to ∼315 Mrad. The Ni/SiC rectifiers show severe reaction of the contact after irradiation at the highest dose, badly degrading the forward current characteristics and increasing the on-state resistance by up to a factor of 6 after irradiation. By sharp contrast, the WSiX/SiC devices show little deterioration of the contact with the same conditions and changes in on-state resistance of <20%. The WSiX contacts appear promising for applications requiring improved contact stability.
Correlation of field emission and surface microstructure of vertically aligned carbon nanotubes
Authors: Jo S. H. , Tu Y. , Huang Z. P. , Carnahan D. L. , Huang J. Y. , Wang D. Z. , Ren Z. F.
Published: January 2004

Two kinds of distinctive field emission behaviors were observed on vertically aligned multiwall carbon nanotube (CNT) films grown by hot filament dc-plasma enhanced chemical vapor deposition. Some samples have stable emission current for more than 60 h (type I), while others degrade substantially in the first 16 h (type II). During the field emission measurement, a brief exposure to air led an abrupt decrease of emission current of all samples. But subsequent reevacuation made type I samples recover the emission current fully, whereas type II samples were damaged permanently reflecting on the irrecoverable emission current. Microstructure studies by transmission electron microscope clearly showed that the stable emission is due to a surface passivation of CNTs by a thin layer of amorphous carbon that prevents CNTs from reacting with ambient gases, e.g., oxygen, during air exposure.
Compositional mapping of surfaces in atomic force microscopy by excitation of the second normal mode of the microcantilever
Authors: Rodrı́guez Tomás R. , Garcı́a Ricardo
Published: January 2004

We propose a method for mapping the composition of a surface by using an amplitude modulation atomic force microscope operated without tip-surface mechanical contact. The method consists in exciting the first two modes of the microcantilever. The nonlinear dynamics of the tip motion, the coupling of its first two modes, and the sensitivity of the second mode to long-range attractive forces allows us to use this mode to probe compositional changes while the signal from the first mode is used to image the sample surface. We demonstrate that the second mode has a sensitivity to surface force variations below 10−11 N.
InAs/InAsP composite channels for antimonide-based field-effect transistors
Authors: Lin H.-K. , Kadow C. , Dahlström M. , Bae J.-U. , Rodwell M. J. W. , Gossard A. C. , Brar B. , Sullivan G. , Nagy G. , Bergman J.
Published: January 2004

We report the growth and transport characteristics of stepped InAs/InAs1−xPx quantum wells with AlSb barriers. Electron mobilities and carrier concentrations in these composite stepped quantum wells were studied as a function of growth temperature and phosphorus content. For InAs1−xPx grown at 430 °C substrate temperature (nominal x=0.2), a high 22 500 cm2/V s electron mobility was observed, while 7100 cm2/V s mobility was observed in a single strained InAs1−xPx quantum well layer. Heterostructure field-effect transistors fabricated using the composite quantum wells exhibited increased breakdown voltage and a 14:1 reduction in source-drain dc conduction when compared to a similar InAs-channel device.
Layer-by-layer diamond-like woodpile structure with a large photonic band gap
Authors: Maldovan Martin , Thomas Edwin L. , Carter Craig W.
Published: January 2004

A layer-by-layer periodic dielectric structure with a large photonic band gap is presented. It consists of a layer-by-layer approximation to the triply periodic bicontinuous level set D surface structure having diamond (Fd3m) symmetry. The structure retains the ease of fabrication of the standard woodpile while increasing the maximum quality factor of the gap by 28%. Photonic band gap properties of this structure were calculated using the plane-wave method and its band gap optimized at a fixed index contrast of 3.6:1.
Dynamic array of dark optical traps
Authors: Daria Vincent Ricardo , Rodrigo Peter John , Glückstad Jesper
Published: January 2004

A dynamic array of dark optical traps is generated for simultaneous trapping and arbitrary manipulation of multiple low-index microstructures. The dynamic intensity patterns forming the dark optical trap arrays are generated using a nearly loss-less phase-to-intensity conversion of a phase-encoded coherent light source. Two-dimensional input phase distributions corresponding to the trapping patterns are encoded using a computer-programmable spatial light modulator, enabling each trap to be shaped and moved arbitrarily within the plane of observation. We demonstrate the generation of multiple dark optical traps for simultaneous manipulation of hollow “air-filled” glass microspheres suspended in an aqueous medium.
Bulk nanostructure formation directly from the multicomponent alloy melt
Authors: Li Jian-Min
Published: January 2004

The first bulk homogeneous nanocrystalline Zr60Al15Ni10Co15 (at. %) alloy prepared by melt casting without the amorphous matrix is reported. In this work, the complete grain refinement directly by solidification processing, when qualitatively compared to the previously reported nanocrystallization by postdevitrification of amorphous alloy solid precursors, produces nanograins that have a relatively narrower size range (7.4 nm in average) and are randomly oriented. The total inhomogeneous chemical affinity of the multicomponent alloy was proposed to thermodynamically favor the three-dimensional nanoscale nucleation from alloy melts. Clustering of different atoms in the ZrAlNiCo alloy occurs while the material is still in the molten state.
Impact of carbon on trap states in n-type GaN grown by metalorganic chemical vapor deposition
Authors: Armstrong A. , Arehart A. R. , Moran B. , DenBaars S. P. , Mishra U. K. , Speck J. S. , Ringel S. A.
Published: January 2004

The effect of excess C incorporation on the deep level spectrum of n-type GaN grown by metalorganic chemical vapor deposition was investigated. Low-pressure (LP) growth conditions were used to intentionally incorporate excess C compared to atmospheric pressure (AP) growth conditions. GaN samples with high C content are found to be highly resistive, and samples codoped with C and Si are heavily compensated. From a comparison of deep level optical spectroscopy and deep level transient spectroscopy measurements of the LP-grown codoped GaN:C:Si sample with the AP-grown unintentionally doped GaN, two deep levels at Ec−Et=1.35 and 3.28 eV are observed to have a direct relation to excess C incorporation. Comparing these activation energies to previous theoretical studies strongly suggests that the levels may be associated with a C interstitial and CN defect, respectively. These results suggest that C forms not only a shallow acceptor level but also a deep acceptor level in GaN, and these levels contribute to the compensation of the free carriers in n-type GaN:C.
Pulsed deposition of metal–oxide thin films using dual metal precursors
Authors: Conley J. F. , Ono Y. , Tweet D. J. , Solanki R.
Published: January 2004

A technique for depositing high-dielectric-constant metal–oxide thin films is demonstrated that consists of alternating pulses of metal–chloride precursors and Hf(NO3)4 in which Hf(NO3)4 is used as an oxidizing agent as well as a metal source. The use of Hf(NO3)4, rather than a separate oxidizing agent such as H2O, minimizes the potential for oxidation of the Si interface. Unlike HfCl4, a widely used precursor, the high reactivity of Hf(NO3)4 initiates uniform deposition on H-terminated Si beginning with the first pulse. Effective dielectric constants obtained for HfO2 films produced by this method were comparable to HfO2 films deposited using other methods and the leakage current densities were three orders of magnitude less than SiO2 of the same equivalent thickness. Deposition of HfAlOx and HfZrOx ternary oxide films was also examined. The deposition rate for films produced using this method is greater than one monolayer per cycle, indicating a mechanism that is different from standard atomic-layer deposition.
Hydrogen ion beam generated by a current-free double layer in a helicon plasma
Authors: Charles C.
Published: January 2004

A current-free double layer in an expanding hydrogen helicon discharge (13.56 MHz) has been discovered by measuring a beam of hydrogen ions at the low potential side of the double layer. The ion beam is supersonic (∼2.1cs) and is detected using a retarding field energy analyzer positioned downstream of the double layer for pressures below a few mTorr and for radio frequency powers up to 1800 W.
Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor
Authors: Launey T. , Endo S. , Sakai R. , Harano J. , Ito M.
Published: January 2004

Phosphorylation of synaptic (
RS
)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) (AMPA) receptors (AMPARs) is an essential component of cerebellar long-term depression (LTD), a form of synaptic plasticity involved in motor learning. Here, we report that protein phosphatase 2A (PP-2A) plays a specific role in controlling synaptic strength and clustering of AMPARs at synapses between granule cells and Purkinje cells. In 22- to 35-day cerebellar cultures, specific inhibition of postsynaptic PP-2A by fostriecin (100 nM) or cytostatin (10–60 μM) induced a gradual and use-dependent decrease of synaptic current evoked by the stimulation of a single granule cell, without altering receptor kinetics nor passive electrical properties. By contrast, PP-2A inhibition had no effect on immature Purkinje cells (12–15 days). Concurrent PP-2A inhibition and AMPAR stimulation induced a reduction of miniature synaptic currents and a reduction of AMPAR density at synapses. Either PP-2A inhibitor alone or AMPA stimulation alone had no significant effect. Inhibition of PP-1 by inhibitor 1 (10–27 units/μl) had no effect on synaptic current. Synaptic depression induced by PP-2A inhibition occluded subsequent induction of LTD by conjunctive stimulation and was abolished by a calcium chelator or a protein kinase inhibitor, suggesting a shared molecular pathway and involvement of PP-2A in LTD induction.
A functional Ni-Ni-[4Fe-4S] cluster in the monomeric acetyl-CoA synthase from
Carboxydothermus hydrogenoformans
Authors: Svetlitchnyi Vitali , Dobbek Holger , Meyer-Klaucke Wolfram , Meins Thomas , Thiele Bärbel , Römer Piero , Huber Robert , Meyer Ortwin
Published: January 2004

In anaerobic microorganisms employing the acetyl-CoA pathway, acetyl-CoA synthase (ACS) and CO dehydrogenase (CODH) form a complex (ACS/CODH) that catalyzes the synthesis of acetyl-CoA from CO, a methyl group, and CoA. Previously, a [4Fe-4S] cubane bridged to a copper-nickel binuclear site (active site cluster A of the ACS component) was identified in the ACS
Mt
/CODH
Mt
from
Moorella thermoacetica
whereas another study revealed a nickel-nickel site in the open form of ACS
Mt
, and a zink-nickel site in the closed form. The ACS
Ch
of the hydrogenogenic bacterium
Carboxydothermus hydrogenoformans
was found to exist as an 82.2-kDa monomer as well as in a 1:1 molar complex with the 73.3-kDa CODHIII
Ch
. Homogenous ACS
Ch
and ACS
Ch
/CODHIII
Ch
catalyzed the exchange between [1-
14
C]acetyl-CoA and
12
CO with specific activities of 2.4 or 5.9 μmol of CO per min per mg, respectively, at 70°C and pH 6.0. They also catalyzed the synthesis of acetyl-CoA from CO, methylcobalamin, corrinoid iron-sulfur protein, and CoA with specific activities of 0.14 or 0.91 μmol of acetyl-CoA formed per min per mg, respectively, at 70°C and pH 7.3. The functional cluster A of ACS
Ch
contains a Ni-Ni-[4Fe-4S] site, in which the positions proximal and distal to the cubane are occupied by Ni ions. This result is apparent from a positive correlation of the Ni contents and negative correlations of the Cu or Zn contents with the acetyl-CoA/CO exchange activities of different preparations of monomeric ACS
Ch
, a 2.2-Å crystal structure of the dithionite-reduced monomer in an open conformation, and x-ray absorption spectroscopy.
Phylogenetic evidence for the early evolution of microcystin synthesis
Authors: Rantala Anne , Fewer David P. , Hisbergues Michael , Rouhiainen Leo , Vaitomaa Jaana , Börner Thomas , Sivonen Kaarina
Published: January 2004

Cyanobacteria are a prolific source of secondary metabolites, including compounds with toxic and enzyme-inhibiting activities. Microcystins and nodularins are the end products of a secondary metabolic pathway comprised of mixed polyketide synthases and nonribosomal peptide synthetases. Both peptides are potent natural toxins produced by distantly related genera of cyanobacteria. Horizontal gene transfer is thought to play a role in the sporadic distribution of microcystin producers among cyanobacteria. Our phylogenetic analyses indicate a coevolution of housekeeping genes and microcystin synthetase genes for the entire evolutionary history of the toxin. Hence they do not corroborate horizontal transfer of genes for microcystin biosynthesis between the genera. The sporadic distribution of microcystin synthetase genes in modern cyanobacteria suggests that the ability to produce the toxin has been lost repeatedly in the more derived lineages of cyanobacteria. The data we present here strongly suggest that the genes encoding nodularin synthetase are recently derived from those encoding microcystin synthetase.
Design of genetic networks with specified functions by evolution
in silico
Authors: François Paul , Hakim Vincent
Published: January 2004

Recent studies have provided insights into the modular structure of genetic regulatory networks and emphasized the interest of quantitative functional descriptions. Here, to provide
a priori
knowledge of the structure of functional modules, we describe an evolutionary procedure
in silico
that creates small gene networks performing basic tasks. We used it to create networks functioning as bistable switches or oscillators. The obtained circuits provide a variety of functional designs, demonstrate the crucial role of posttranscriptional interactions, and highlight design principles also found in known biological networks. The procedure should prove helpful as a way to understand and create small functional modules with diverse functions as well as to analyze large networks.
Monitoring protein stability and aggregationin vivoby real-time fluorescent labeling
Authors: Ignatova Zoya , Gierasch Lila M.
Published: January 2004

In vivofluorescent labeling of an expressed protein has enabled the observation of its stability and aggregation directly in bacterial cells. Mammalian cellular retinoic acid-binding protein I (CRABP I) was mutated to incorporate in a surface-exposed omega loop the sequence Cys-Cys-Gly-Pro-Cys-Cys, which binds specifically to a biarsenical fluorescein dye (FlAsH). Unfolding of labeled tetra-Cys CRABP I is accompanied by enhancement of FlAsH fluorescence, which made it possible to determine the free energy of unfolding of this protein by urea titration in cells and to follow in real time the formation of inclusion bodies by a slow-folding, aggregationprone mutant (FlAsH-labeled P39A tetra-Cys CRABP I). Aggregationin vivodisplayed a concentration-dependent apparent lag time similar to observations of protein aggregation in purifiedin vitromodel systems.
A proteomic approach for the analysis of instantly released wound and immune proteins in
Drosophila melanogaster
hemolymph
Authors: Vierstraete Evy , Verleyen Peter , Baggerman Geert , D'Hertog Wannes , Van den Bergh Gert , Arckens Lutgarde , De Loof Arnold , Schoofs Liliane
Published: January 2004

Insects respond to microbial infection by the rapid and transient expression of several genes encoding antibacterial peptides. In this paper we describe a powerful technique, two-dimensional difference gel electrophoresis, that, when combined with mass spectrometry, can be used to study the immune response of
Drosophila melanogaster
at the protein level. By comparatively analyzing the hemolymph proteome of 2,000 third-instar
Drosophila
larvae, we identified 10 differential proteins that appear in the fruit fly hemolymph very early after an immune-challenge with lipopolysaccharides. These proteins can be assigned to the immune response, because they are not induced after sterile injury. Reduction of intergel variability or quantification problems related to conventional two-dimensional electrophoresis and improvement of image analysis were achieved by the use of two fluorescent dyes to label the two different protein samples. Some of the immune-induced proteins, such as thioester-containing protein 2, can be assigned to specific aspects of the immune response; others were already reported as being involved in stress response. An immune-induced protein (CG18594) is homologous to a mammalian serine protease inhibitor that mediates the mitogen-activated protein kinase and the NF-κB signaling pathways. In addition, a number of proteins that had not been associated with the immune response before were isolated and identified, and some of these were still present in the hemolymph 4 h after injury. Determining the function of all of these immune-induced proteins represents an exciting challenge for increasing our knowledge of insect immunity.
IL-13 receptor α 2 down-modulates granulomatous inflammation and prolongs host survival in schistosomiasis
Authors: Mentink-Kane Margaret M. , Cheever Allen W. , Thompson Robert W. , Hari Danielle M. , Kabatereine Narcis B. , Vennervald Birgitte J. , Ouma John H. , Mwatha Joseph K. , Jones Frances M. , Donaldson Debra D. , Grusby Michael J. , Dunne David W. , Wynn Thomas A.
Published: January 2004

An important feature of many chronic parasitic infections is the ability of the invading pathogen and host to establish a compromise, which ensures successful parasitism without killing the infected host. For many helminth infections, down-modulating the immune response is critical because persistent inflammation can become more damaging to the host than the invading pathogen itself. Such is the case with schistosomiasis mansoni, where chronic granulomatous inflammation in the liver causes portal hypertension, porto-pulmonary shunting, bleeding from collateral bypass vessels, and eventual death if not suppressed effectively. CD4+T helper type 2 cells (Th2) (secreting IL-4, IL-5, and IL-13) characterize the host response afterSchistosoma mansoniinfection, and recent studies have identified IL-13 as the principal mediator of hepatic fibrosis. Here, we show that the IL-13 receptor α 2 (IL-13Rα2) is a critical mediator of immune down-modulation, identifying the receptor as a life-sustaining off signal for chronic and pernicious inflammation in schistosomiasis.
Hatching failure increases with severity of population bottlenecks in birds
Authors: Briskie James V. , Mackintosh Myles
Published: January 2004

Severe bottlenecks can reduce genetic diversity and increase inbreeding as individuals are forced to mate with close relatives, but it is unknown at what minimum population size the negative fitness consequences of bottlenecks are expressed. The New Zealand avifauna contains a large number of species that have gone through bottlenecks of varying severity, providing an exceptional opportunity to test this question by using the comparative method. Using decreased hatchability as a measure of fitness costs, we found that hatching failure was significantly greater among both native and introduced species that had passed through bottlenecks of <150 individuals. Comparisons between pre- and postbottleneck populations of introduced species suggest that hatching problems arise even in populations founded by <600 individuals. Our study confirms that hatching failure is widespread and persistent among birds passing through severe bottlenecks and that the population sizes at which this fitness cost is expressed are several times greater than the number of individuals currently used to found most new populations of endangered species. We recommend that conservation managers revise the protocols they use for reintroductions or they may unwittingly reduce the long-term viability of the species they are trying to save.
Identification of calcium- and nitric oxide-regulated genes by differential analysis of library expression (DAzLE)
Authors: Li Huiwu , Gu Xiujing , Dawson Valina L. , Dawson Ted M.
Published: January 2004

Using a method of expression profiling called differential analysis of cDNA library expression (DAzLE), we report the expression profile of late response genes in a model of activity-dependent neuronal survival and neurite outgrowth. Using DAzLE, we isolated differentially expressed genes from cultured rat embryonic cortical neurons after KCl (50 mM)-mediated membrane depolarization. We identified 469 activity-dependent regulated genes, of which 174 are genes of unknown function. The regulation of 63 genes was found to be nitric oxide (NO)-dependent. Identifiable genes fell into several major categories, including signal transduction pathways, neuronal development, DNA replication, gene transcription, protein metabolism, energy regulatory proteins, and antiapoptotic proteins. These genes may be important in activity-dependent neuron survival and development. Furthermore, these late response genes provide the tools to begin to investigate downstream events in activity-dependent neuronal survival and development. The major advantage of DAzLE is that it provides a nearly complete and relatively comprehensive differential screening profile that has the potential to be a powerful and useful tool in other fields of study.
Electrocardiographic and other cardiac anomalies in β-glucuronidase-null mice corrected by nonablative neonatal marrow transplantation
Authors: Schuldt A. J. T. , Hampton T. J. , Chu V. , Vogler C. A. , Galvin N. , Lessard M. D. , Barker J. E.
Published: January 2004

Cardiovascular manifestations of lysosomal storage disease (LSD) are a significant health problem for affected patients. Infantileonset cardiac disease, because of its rapid progression, is usually treated symptomatically. Therapy in older patients includes valve replacement and bone marrow (BM) transplantation, both of which are life threatening in the already debilitated patients. Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in β-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly syndrome), develop progressive LSD unless provided with GUSB early in life. The BM recipients retained GUSB+ donor cells in the peripheral blood and heart until necropsy at >11 months of age. The enzyme β-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (
P
= 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart/body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of LSD.
Transcriptome-based determination of multiple transcription regulator activities in
Escherichia coli
by using network component analysis
Authors: Kao Katy C. , Yang Young-Lyeol , Boscolo Riccardo , Sabatti Chiara , Roychowdhury Vwani , Liao James C.
Published: January 2004

Cells adjust gene expression profiles in response to environmental and physiological changes through a series of signal transduction pathways. Upon activation or deactivation, the terminal regulators bind to or dissociate from DNA, respectively, and modulate transcriptional activities on particular promoters. Traditionally, individual reporter genes have been used to detect the activity of the transcription factors. This approach works well for simple, non-overlapping transcription pathways. For complex transcriptional networks, more sophisticated tools are required to deconvolute the contribution of each regulator. Here, we demonstrate the utility of network component analysis in determining multiple transcription factor activities based on transcriptome profiles and available connectivity information regarding network connectivity. We used
Escherichia coli
carbon source transition from glucose to acetate as a model system. Key results from this analysis were either consistent with physiology or verified by using independent measurements.
Entropic switch regulates myristate exposure in the HIV-1 matrix protein
Authors: Tang Chun , Loeliger Erin , Luncsford Paz , Kinde Isaac , Beckett Dorothy , Summers Michael F.
Published: January 2004

The myristoylated matrix protein (myr-MA) of HIV functions as a regulator of intracellular localization, targeting the Gag precursor polyprotein to lipid rafts in the plasma membrane during virus assembly and dissociating from the membrane during infectivity for nuclear targeting of the preintegration complex. Membrane release is triggered by proteolytic cleavage of Gag, and it has, until now, been believed that proteolysis induces a conformational change in myr-MA that sequesters the myristyl group. NMR studies reported here reveal that myr-MA adopts myr-exposed [myr(e)] and -sequestered [myr(s)] states, as anticipated. Unexpectedly, the tertiary structures of the protein in both states are very similar, with the sequestered myristyl group occupying a cavity that requires only minor conformational adjustments for insertion. In addition, myristate exposure is coupled with trimerization, with the myristyl group sequestered in the monomer and exposed in the trimer (
K
assoc
= 2.5 ± 0.6 × 10
8
M
–2
). The equilibrium constant is shifted ≈20-fold toward the trimeric, myristate-exposed species in a Gag-like construct that includes the capsid domain, indicating that exposure is enhanced by Gag subdomains that promote self-association. Our findings indicate that the HIV-1 myristyl switch is regulated not by mechanically induced conformational changes, as observed for other myristyl switches, but instead by entropic modulation of a preexisting equilibrium.
The catalytic cycle of cytochrome
c
oxidase is not the sum of its two halves
Authors: Bloch Dmitry , Belevich Ilya , Jasaitis Audrius , Ribacka Camilla , Puustinen Anne , Verkhovsky Michael I. , Wikström Mårten
Published: January 2004

Membrane-bound cytochrome
c
oxidase catalyzes cell respiration in aerobic organisms and is a primary energy transducer in biology. The two halves of the catalytic cycle may be studied separately: in an oxidative phase, the enzyme is oxidized by O
2
, and in a reductive phase, the oxidized enzyme is reduced before binding the next O
2
molecule. Here we show by time-resolved membrane potential and pH measurements with cytochrome oxidase liposomes that, with both phases in succession, two protons are translocated during each phase, one during each individual electron transfer step. However, when the reductive phase is not immediately preceded by oxidation, it follows a different reaction pathway no longer coupled to proton pumping. Metastable states with altered redox properties of the metal centers are accessed during turnover and relax when external electron donors are exhausted but recover after enzyme reduction and reoxidation by O
2
. The efficiency of ATP synthesis might be regulated by switching between the two catalytic pathways.
Context-dependent regulation of GATA-1 by friend of GATA-1
Authors: Letting Danielle L. , Chen Ying-Yu , Rakowski Carrie , Reedy Sarah , Blobel Gerd A.
Published: January 2004

The transcription factor GATA-1 and its cofactor, friend of GATA-1 (FOG-1), are essential for normal erythroid development. FOG-1 physically interacts with GATA-1 to augment or inhibit its activity. The mechanisms by which FOG-1 regulates GATA-1 function are unknown. By using an assay that is based on the phenotypic rescue of a GATA-1-null erythroid cell line, we found that a conditional form of GATA-1 (GATA-1-ER) strongly induced histone acetylation at the β-major globin promoter
in vivo
, consistent with previous results. In contrast, GATA-1 bearing a point mutation that impairs FOG-1 binding [GATA-1(V205M)-ER] failed to induce high levels of histone acetylation at this site. However, at DNase I-hypersensitive site (HS)3 of the β-globin locus control region, GATA-1-induced histone acetylation was FOG-1-independent. Because the V205M mutation does not disrupt GATA-1 binding to DNA templates
in vitro
, we were surprised to find that
in vivo
GATA-1(V205M)-ER fails to bind the β-globin promoter. However, at HS3, DNA binding by GATA-1 was FOG-1-independent, thus correlating histone acetylation with GATA-1 occupancy. Examination of additional GATA-1-dependent regulatory elements showed that the interaction with FOG-1 is required for GATA-1 occupancy at select sites, such as HS2, but is dispensable at others, including the FOG-1-independent GATA-1 target gene
EKLF
. Remarkably, at the
GATA
-2 gene, which is repressed by GATA-1, interaction with FOG-1 was dispensable for GATA-1 occupancy and was required for transcriptional inhibition and histone deacetylation. These results indicate that FOG-1 employs distinct mechanisms when cooperating with GATA-1 during transcriptional activation and repression.
H-bonded N-heterocyclic base-pair phototautomerizational potential barrier and mechanism: The 7-azaindole dimer
Authors: Catalán J. , Pérez P. , del Valle J. C. , de Paz J. L. G. , Kasha M.
Published: January 2004

A theoretical analysis of the double proton transfer (PT) in a hydrogen-bonded N-heterocyclic base pair is presented. The calculated (time-dependent density functional theory) double PT barrier calculated for the concerted process of the 7-azaindole C
2h
dimer in the first excited singlet electronic state S
1
conforms well to the kinetic data and the photophysical evidence reported in this article. The calculated PT energy barrier of 4.8 kcal/mol height, and the corresponding zero point energy value, yield for the S
1
state an activation energy barrier of 0.3 kcal/mol. This finding implies that the double PT concerted process is almost barrierless, confirming previous experiments. Upon N-H deuteration of the 7-azaindole dimer, the theoretical excited-state activation energy for the double deuterium transfer is determined to be 1.4 kcal/mol, in agreement with experiment, which in low-temperature spectroscopy is shown to negate excited-state double-deuteron transfer.
Physical and functional interaction of androgen receptor with calmodulin in prostate cancer cells
Authors: Cifuentes Eugenia , Mataraza Jennifer M. , Yoshida Barbara A. , Menon Mani , Sacks David B. , Barrack Evelyn R. , Reddy G. Prem-Veer
Published: January 2004

Ca
2+
and calmodulin (CaM) play a critical role in proliferation and viability of a wide variety of cells, including prostate cancer cells. We examined two prostate cancer cell lines, androgen-sensitive LNCaP and androgen-independent PC-3. Proliferation of LNCaP cells was six to eight times more sensitive to the inhibitory effect of the CaM antagonist
N-
(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) than were PC-3 cells. Because LNCaP cell proliferation is sensitive to stimulation by androgen, we assessed the physical and functional interaction between androgen receptor (AR) and CaM. We observed tight binding of AR to CaM when LNCaP cell extracts were subjected to CaM-affinity column chromatography. AR binding to CaM was Ca
2+
-dependent and was inhibited by pretreatment of the cell extracts with W-7. Using immunofluorescence staining and confocal microscopy, we demonstrated colocalization of AR and CaM in the nucleus of LNCaP cells. Furthermore, the functional relevance of AR-CaM interactions in intact cells was revealed by the observation that W-7 was as effective as Casodex, an antiandrogen, in blocking AR-regulated expression of prostate-specific antigen in LNCaP cells. AR seems to interact with CaM directly because purified human AR could bind to CaM-agarose, and CaM could be detected in AR-immunoprecipitate prepared from purified soluble proteins. These studies provide direct evidence for physical and functional interaction between AR and CaM and suggest the potential usefulness of CaM antagonists in blocking AR activity in prostate cancer.
Loss of CDX1 expression in colorectal carcinoma: Promoter methylation, mutation, and loss of heterozygosity analyses of 37 cell lines
Authors: Wong N. A. C. S. , Britton M. P. , Choi G. S. , Stanton T. K. , Bicknell D. C. , Wilding J. L. , Bodmer W. F.
Published: January 2004

Expression of the homeobox protein CDX1 is lost or reduced in a significant proportion of colorectal carcinomas (CRCs) but the underlying mechanism for this is unclear. We have demonstrated absence of CDX1 mRNA expression in 7 of 37 CRC cell lines and shown that all 7 cell lines have a methylated
CDX1
promoter. Twenty-five cell lines showed both CDX1 mRNA expression and an unmethylated
CDX1
promoter. The five remaining cell lines had a partially methylated
CDX1
promoter and all expressed CDX1 mRNA; when treated with the demethylating agent, 5-aza-2′-deoxycytidine, these five cell lines all showed increased CDX1 expression. No mutations were found in the promoter and coding regions of
CDX1
. One polymorphism was demonstrated in each of the promoter, 5′ UTR, and coding region of exon 1 of
CDX1
, but there were no associations between CDX1 mRNA expression and different polymorphic genotypes. Similarly, there was no association between CDX1 mRNA expression and loss of heterozygosity at the
CDX1
locus. In conclusion, absence or reduction of CDX1 expression in CRC seems to be primarily regulated by promoter methylation and is probably selected for because of its impact on the differentiation of colonocytes.
Residual integrated viral DNA after hepadnavirus clearance by nucleoside analog therapy
Authors: Summers Jesse , Mason William S.
Published: January 2004

We determined the frequency of integrated viral DNA in the livers of three woodchucks chronically infected with the woodchuck hepatitis virus before and during 30 weeks of therapy with the nucleoside analog L-FMAU [1-(2-fluoro-5-methyl-beta,
l
-arabinofuranosyl)uracil, clevudine]. We found that although viral covalently closed circular DNA declined 20- to 100-fold, integrated viral DNA showed no discernable decrease over the course of treatment. Thus, chemotherapeutic clearance of covalently closed circular DNA did not involve the replacement of the infected hepatocyte population with uninfected progenitors, but rather, uninfected hepatocytes in the treated liver were derived from the infected hepatocyte population. The frequency of integrated DNA in chronically infected woodchucks was found to be 1 or 2 orders of magnitude higher than that in transiently infected woodchucks, implying that integration and other genomic damage accumulate over the duration of infection. Our results indicate that genetic changes from this damage remain in the liver even while virus infection is cleared and argue for early antiviral intervention in chronic hepatitis.
Identification of Lhp1p-associated RNAs by microarray analysis in
Saccharomyces cerevisiae
reveals association with coding and noncoding RNAs
Authors: Inada Maki , Guthrie Christine
Published: January 2004

La is a conserved eukaryotic RNA-binding protein best known for its role in the biogenesis of noncoding RNAs transcribed by RNA polymerase III. To broaden our understanding of the function of the La homologous protein (Lhp1) in
Saccharomyces cerevisiae
, we have taken a genomics approach. Lhp1 ribonucleoprotein complexes were immunoprecipitated and bound RNAs were examined by hybridization to whole-genome microarrays that include >6,000 ORFs, documented noncoding RNAs, and the intervening intergenic regions. Demonstrating the validity of this approach, associations with previously known Lhp1p-associated RNAs were detected and associations with additional noncoding RNAs, including multiple tRNAs and small nucleolar RNAs, were revealed. Indicating that this approach provides a robust method for discovering RNAs, the data also identify associations between Lhp1p and several intergenic regions, three of which encode the recently annotated putative snoRNAs:
RUF1
,
RUF2
, and
RUF3
. Unexpectedly, we find that Lhp1p is also associated with a subset of coding mRNAs. These mRNAs include many ribosomal protein transcripts as well as the mRNA encoding Hac1p, a transcription factor required during the unfolded protein stress response. In cells lacking
LHP1
, Hac1p levels are decreased 2- to 3-fold, whereas no changes are detected in the levels of spliced or unspliced HAC1 mRNA or in the stability of Hac1p. Finally, although
LHP1
is dispensable for growth under standard conditions, we find that it is required when the unfolded protein response is induced at elevated temperatures. These results suggest that Lhp1p may play a novel role in the translation of one or more cellular mRNAs.