bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical phonon spectra of GaP nanoparticles prepared by nanochemistry
Authors: Manciu F. S. , Sahoo Y. , MacRae D. J. , Furis M. , McCombe B. D. , Prasad P. N.
Published: June 2003

Gallium phosphide (GaP) nanoparticles have been synthesized by colloidal nanochemistry with two different surfactants: trioctylphosphine oxide and dodecylamine. Transverse optical (bulk) and surface optical phonons associated with the GaP nanoparticles were observed and studied experimentally by infrared transmission spectroscopy of a solid dispersion of these nanoparticles in cesium iodide pellets. These vibrational properties of the nanoparticles were used to obtain information about the crystallinity and surface interactions. The crystallinity and the stoichiometry of the samples were also examined and characterized by transmission electron microscopy, electron diffraction, and energy dispersive x-ray spectroscopy.
Structures of nitrided Si(001) surfaces: First-principles theoretical study
Authors: Higai Shin’ichi , Ohno Takahisa
Published: June 2003

First-principles theoretical calculations for nitrided Si(001) surfaces are presented. We examined the structure and stability of ordered nitrided surfaces with various coverages of N and H atoms. For the 2×2 ordered reconstruction observed in very recent experiments, we propose a structural model, where N atoms are adsorbed into Si dimer centers and also into back bonds, and those in the dimer centers are dimerized. We also discuss the nitridation process.
Effect of Li doping on the magnetotransport properties of La0.7Ca0.3−yLiyMnO3 system: Decrease of metal–insulator transition temperature
Authors: Bhattacharya Sayani , Mukherjee R. K. , Chaudhuri B. K. , Yang H. D.
Published: June 2003

With increasing the Li doping level in La0.7Ca0.3−yLiyMnO3 (0⩽y⩽0.3), the system is driven from a higher-conductivity regime to a lower-conductivity regime, which is in sharp contrast with the behavior of Na or K doping. Compared to those of K or Na, the ionic radius of Li is much smaller than that of Ca. Therefore, substitution of Ca by Li results in a smaller average A-site radius, narrowing the bandwidth and hence enhancing the band gap and resistivity. The effect of random disorder of La3+ and A2+ also plays an important role leading to charge localization.
Large frequency dependence of lowered maximum dielectric constant temperature of LiTaO3 nanocrystals dispersed in mesoporous silicate
Authors: Kohiki Shigemi , Nogami Shinichiro , Kawakami Shintaro , Takada Syozo , Shimooka Hirokazu , Deguchi Hiroyuki , Mitome Masanori , Oku Masaoki
Published: June 2003

A large frequency dependence of the maximum dielectric constant temperature was observed for LiTaO3 nanocrystals (the diameter ≈20 Å) dispersed in mesoporous silicate. At the applied field frequency of 100 kHz, the maximum temperatures in the real and imaginary parts were 365 and 345 °C, respectively. The maximum temperature in the real part is apparently lower than the paraelectric–ferroelectric transition temperature (645 °C) of bulk LiTaO3. The maximum temperature in the imaginary part rose from 285 to 420 °C with increasing frequency from 10 to 1000 kHz. Since the bulk LiTaO3 shows no relaxor behavior, such superparaelectric behavior is obviously a consequence of nanominiaturization of LiTaO3 crystal and insignificant cooperative interactions between the nanoparticles.
High-resolution near-field spectroscopy investigation of GaN laterally overgrown structures on SiC
Authors: Hitzel F. , Hangleiter A. , Miller S. , Weimar A. , Brüderl G. , Lell A. , Härle V.
Published: June 2003

We investigated epitaxial lateral overgrown GaN structures with different wing tilt using a spectroscopic scanning near-field optical microscope (spectroscopic SNOM), which takes a complete optical spectrum at each point of a sample surface. From these measurements, we obtain information about strain at different points of the surface, and comparing emission intensity between regions of lateral growth and vertical growth, we directly see the efficiency of defect density reduction. For the high wing-tilt sample, an increased defect density at the window–wing interface could be identified.
Room-temperature low-voltage electroluminescence in amorphous carbon nitride thin films
Authors: Reyes R. , Legnani C. , Ribeiro Pinto P. M. , Cremona M. , de Araújo P. J. G. , Achete C. A.
Published: June 2003

White-blue electroluminescent emission with a voltage bias less than 10 V was achieved in rf sputter-deposited amorphous carbon nitride (a-CN) and amorphous silicon carbon nitride (a-SiCN) thin-film-based devices. The heterojunction structures of these devices consist of: Indium tin oxide (ITO), used as a transparent anode; amorphous carbon film as an emission layer, and aluminum as a cathode. The thickness of the carbon films was about 250 Å. In all of the produced diodes, a stable visible emission peaked around 475 nm is observed at room temperature and the emission intensity increases with the current density. For an applied voltage of 14 V, the luminance was about 3 mCd/m2. The electroluminescent properties of the two devices are discussed and compared.
Is Cu60Ti10Zr30 a bulk glass-forming alloy?
Authors: Jiang J. Z. , Saida J. , Kato H. , Ohsuna T. , Inoue A.
Published: June 2003

The microstructures of Cu60Ti10Zr30 alloys fabricated by using two different methods, (rods of 2.5 mm in diameter prepared by a copper-mold casting method, and ribbons of about 0.03 mm in thickness prepared by the melt-spinning method), have been investigated by transmission electron microscopy and high-resolution transmission electron microscopy. Surprisingly, we found that the alloy in both geometries contains cubic nanometer-sized crystals of about 5–7 nm in diameter with a lattice parameter of 0.45 nm for ribbons and 7–15 nm in diameter with a lattice parameter of 0.42 nm for rods. Nanocrystals with a significant volume fraction are randomly distributed in the amorphous matrix. The copper element is enriched in nanocrystals while a slightly high zirconium content is found in the matrix. We classify that the Cu60Ti10Zr30 alloy prepared by both of the aforementioned methods is a nanocomposite: Nanocrystals embedded in an amorphous matrix.
Cooperative versus superparamagnetic behavior of dense magnetic nanoparticles in Co80Fe20/Al2O3 multilayers
Authors: Sahoo S. , Petracic O. , Kleemann W. , Stappert S. , Dumpich G. , Nordblad P. , Cardoso S. , Freitas P. P.
Published: June 2003

Spin glasslike cooperative freezing is evidenced at low temperatures in a magnetic nanoparticle system prepared as a discontinuous metal–insulator multilayer [Co80Fe20(0.9 nm)/Al2O3(3 nm)]10. The relaxational behavior clearly deviates from Arrhenius–Néel–Brown-type and rather hints at collective freezing into a spin glass phase below Tg≃61 K. Holelike memory imprinting during a stop-and-wait magnetization procedure corroborates the collective nature of the frozen state. Consequences for future magnetic terabit storage devices are briefly discussed.
Photoluminescence enhancement of colloidal quantum dots embedded in a monolithic microcavity
Authors: Poitras Carl B. , Lipson Michal , Du Hui , Hahn Megan A. , Krauss Todd D.
Published: June 2003

We demonstrate an enhancement of the spontaneous emission from colloidal CdSe quantum dots embedded in a half-wavelength one-dimensional cavity. When embedded in the cavity, the emission of the quantum dots is enhanced by a factor of 2.7. We also show a strong amplification by one order of magnitude in the absorption of the CdSe quantum dots due to the cavity effect.
Vortex nucleation in submicrometer ferromagnetic disks
Authors: Rahm M. , Schneider M. , Biberger J. , Pulwey R. , Zweck J. , Weiss D. , Umansky V.
Published: June 2003

We investigate both experimentally and by means of micromagnetic calculations magnetic states preceding vortex formation in permalloy nanodisks. In experiment, we used micro-Hall sensors fabricated from GaAs/AlGaAs heterojunction material to measure stray field hysteresis loops of individual disks. Micromagnetic calculations involving different micromagnetic codes allowed us to interpret the experimental results. Both calculations and experiments suggest that vortex formation can be reached via different precursor states.
Non-volatile memory cells based on ZnxCd1−xS ferroelectric Schottky diodes
Authors: van der Sluis P.
Published: June 2003

Ferroelectric Schottky diodes were fabricated with n-type Zn0.4Cd0.6S. These devices show promising nonvolatile memory properties and the integration into complementary metal-oxide-semiconductor (CMOS) circuits seems feasible. So far, we have demonstrated on-resistances down to 100 Ω, on/off ratios up to 107, switching voltages below 100 mV, operating temperatures up to 180 °C, and switching times below 50 ns. The devices can be deposited at low temperatures (200 °C) by conventional rf-sputtering and survive the 30-min anneal at 400 °C in forming gas, which is mandatory in CMOS processing.
Development of gold-doped Hg0.79Cd0.21Te for very-long-wavelength infrared detectors
Authors: Shih H. D. , Kinch M. A. , Aqariden F. , Liao P. K. , Schaake H. F. , Nathan V.
Published: June 2003

Gold-doped Hg1−xCdxTe samples of x=0.2067 (in the very-long-wavelength infrared spectral band, with cutoff wavelengths ∼13.2 μm at 77 K) were prepared by tellurium-melt liquid-phase epitaxy. The samples were doped with indium to ∼2×1014 cm−3 and gold to ∼7×1015 cm−3, and were characterized by secondary ion mass spectroscopy, Hall measurements, and minority carrier lifetime measurements. State-of-the-art minority carrier lifetime of ∼0.82 μs was obtained.
Enhanced room-temperature emission in Cr4+ ions containing alumino-silicate glasses
Authors: Batchelor C. , Chung W. J. , Shen S. , Jha A.
Published: June 2003

The Bi2O3 modified alumino-silicate glasses, when excited at 800 nm exhibited a broadband emission of Cr4+ in the range of 1.2 to ∼1.6 μm at room temperature. The mean lifetime of (1E−3A2)→3T1 transition in Cr4+-doped glass at RT was as long as ∼426 μs, enabling the realization of both tunable lasers and broadband fiber amplifiers. The Cr4+ emission at RT also showed the dependency on the excitation wavelength and site distribution within the chosen glass host. A photoinduced charge transfer process from the Cr3+ ion into Cr4+ ion appears to be responsible for the excitation of Cr4+.
Monte Carlo simulation of tunable mid-infrared emission from coupled Wannier–Stark ladders in semiconductor superlattices
Authors: Manenti M. , Compagnone F. , Di Carlo A. , Lugli P. , Scamarcio G. , Rizzi F.
Published: June 2003

We present a theoretical and experimental study on the mid-infrared electroluminescence associated with transitions between electric-field-induced conduction states, forming the Wannier–Stark ladder, in strongly coupled GaAs/AlAs superlattices. The interwell and intrawell radiative transitions in the whole range of electric fields from the moderate localization to the resonance-induced delocalization regimes have been experimentally investigated. Monte Carlo simulations show a very good agreement between experimental and theoretical electroluminescence spectra. Results show that the application of an electric field in the range from 100 to 250 kV/cm shifts the emission peak, related with interwell diagonal transitions between Stark-localized ground states of two adjacent wells, up to the limit corresponding to the merging of this electroluminescence peak with the intersubband emission between excited and ground state of the same well. The theoretical investigation indicates that interwell scattering via LO phonons is responsible for the population of the excited state of the ladder.
Stimulated emission and ultrafast carrier relaxation in AlGaN/GaN multiple quantum wells
Authors: Özgür Ümit , Everitt Henry O. , He Lei , Morkoç Hadis
Published: June 2003

Stimulated emission (SE) and ultrafast carrier relaxation dynamics were measured in two AlxGa1−xN/GaN multiple-quantum-well (MQW) structures, grown in a Ga-rich environment with x=0.2 and 0.3, respectively. The threshold density for SE (Ith≃100 μJ/cm2) was found to be independent of x. Room-temperature, time-resolved, differential transmission measurements mapped the carrier relaxation mechanisms for above barrier energy excitation. Photoexcited carriers are observed to relax into the QWs in <1 ps, while carrier recombination times as fast as 30 ps were measured. For excitation above Ith, SE is shown to deplete carriers in the barriers through a cascaded refilling of the QW state undergoing SE. Similar behavior is seen in an Al0.3Ga0.7N/GaN MQW grown with a N-rich atmosphere, but the relaxation phenomena of all AlGaN MQWs are significantly faster than observed in InGaN MQWs of similar structure.
Growth and optical properties of GaN/AlN quantum wells
Authors: Adelmann C. , Sarigiannidou E. , Jalabert D. , Hori Y. , Rouvière J.-L. , Daudin B. , Fanget S. , Bru-Chevallier C. , Shibata T. , Tanaka M.
Published: June 2003

We demonstrate the growth of GaN/AlN quantum-well structures by plasma-assisted molecular-beam epitaxy by taking advantage of the surfactant effect of Ga. The GaN/AlN quantum wells show photoluminescence emission with photon energies in the range between 4.2 and 2.3 eV for well widths between 0.7 and 2.6 nm, respectively. An internal electric field strength of 9.2±1.0 MV/cm is deduced from the dependence of the emission energy on the well width.
Substrate effect on the crystal structure and ferroelectricity of low-temperature-deposited Pb(Zr, Ti)O3 thin films by metalorganic chemical vapor deposition
Authors: Tokita Kouji , Aratani Masanori , Funakubo Hiroshi
Published: June 2003

Tetragonal Pb(Zr0.35Ti0.65)O3 thin films were deposited at deposition temperatures ranging from 395 °C to 510 °C on (111)Pt/Ti/SiO2/Si, (111)Ir/TiO2/SiO2/Si, and (100)Ru/SiO2/Si substrates by metalorganic chemical vapor deposition. When the deposition temperature was above 415 °C, the remanent polarization (Pr) and the coercive field (Ec) were almost the same for the Pb(Zr0.35Ti0.65)O3 thin films deposited on these substrates. This means that the electrical properties were not significantly affected by the type of substrate above 415 °C. However, at 395 °C, the film deposited on the (111)Pt/Ti/SiO2/Si substrate showed a larger Pr value than those on the (111)Ir/TiO2/SiO2/Si and (100)Ru/SiO2/Si substrates. The lower crystallinity of the films deposited on the (111)Ir/TiO2/SiO2/Si and (100)Ru/SiO2/Si substrates, due to the oxidation of the Ir and Ru surfaces before starting film deposition, thwarts the attainment of good ferroelectricity.
Photoluminescence of a superficial Si nanolayer and an example of its use
Authors: Ley M. , Svrcek V. , Kuznicki Z. T.
Published: June 2003

A characteristic photoluminescence of a superficial Si nanolayer realized by ion implantation has been observed. This effect, being totally independent of those shown recently for a nanoscale Si-layered system, is similar to that produced by Si nanocrystals (Si nc). To visualize the nature and give evidence of this effect, we fabricated samples in two different ways: (i) by incorporation of Si nc into thin SiO2 films deposited on Si wafer by the spin-on-glass method and (ii) by a nanoscale superficial crystalline-Si modification using medium-energy ion implantation and thermal treatment. In both cases the UV-to-red light conversion has been observed to be independent of wafer post-implantation damage. To show the UV-to-red conversion contribution, we use the ion modified superficial Si layer with its well-defined potential barrier, the so-called carrier collection limit. Such a modified Si structure gives us a method of deconvoluting several optoelectronic features observed experimentally on modified Si. The practical realization is compatible with well-established Si technology.
Different dynamic behaviors of Pb(Mg1/3Ta2/3)O3 and Ba(Mg1/3Ta2/3)O3 single crystals studied by micro-Brillouin scattering and dielectric spectroscopy
Authors: Ko Jae-Hyeon , Kojima Seiji , Lushnikov S. G.
Published: June 2003

Acoustic and dielectric properties of Pb(Mg1/3Ta2/3)O3 (PMT) and Ba(Mg1/3Ta2/3)O3 (BMT) single crystals with B-site disorder were obtained in a wide temperature range by micro-Brillouin scattering and dielectric spectroscopy. The temperature dependences of both the dielectric constant and the Brillouin shift of the longitudinal acoustic (LA) mode of BMT showed that there is no structural phase transition below 860 K, consistent with thermal expansion measurements. A low dielectric constant ε∼20 of BMT reflected the low-level flux contamination. PMT crystals showed frequency-dependent dielectric maximum, significant softening of the Brillouin shift of LA mode deviating from the high-temperature linear behavior. The temperature dependence of the maximum relaxation time could be obtained by combining dielectric and acoustic data, which followed the Vogel–Fulcher law with a freezing temperature of 119±6 K. This temperature coincides with that estimated from the frequency dependence of the temperature of the dielectric maximum, which is the evidence of the real freezing of the relaxation-time spectrum of PMT at a finite temperature.
Efficient field emission from single crystalline indium oxide pyramids
Authors: Jia Hongbo , Zhang Ye , Chen Xihong , Shu Jing , Luo Xuhui , Zhang Zhensheng , Yu Dapeng
Published: June 2003

Well-aligned indium oxide pyramids were synthesized on a Ni-coated silicon (100) substrate by a chemical vapor deposition. Scanning electron microscopy and x-ray diffraction investigations show that these pyramids present a tetragonal morphology and single-crystalline cubic bixbyite structure. The size control of the pyramids was achieved by varying the growth temperature. Field-emission characteristics of the as-grown indium oxide pyramids were measured. The field-emission current density of the nanopyramids (average size: ∼180 nm) reached about 1 mA/cm2 at a threshold field of about 6.0 V/μm, which is comparable to that of carbon nanotubes, and can guarantee sufficient luminescence brightness in a flat panel display.
High critical current density in iron-clad MgB2 tapes
Authors: Fang H. , Padmanabhan S. , Zhou Y. X. , Salama K.
Published: June 2003

Iron-clad MgB2 superconducting tapes with a MgB2 core cross-section area of 1.07×10−3 cm2 were fabricated using the standard powder-in-tube method. The starting precursor was ultrafine Mg and B mixture powder prepared by high-energy ball milling. Very good grain connections as well as grain refinement were obtained in tapes annealed at 850 °C. Under a 1.5-T external magnetic field, Jc is 1.07×105 and 6.54×103 A/cm2 at 20 and 30 K, respectively. An extrapolation to zero field at 20 K gives a Jc of 3.0×105 A/cm2.
Low-voltage organic electroluminescence device with an ultrathin, hybrid structure
Authors: Heithecker Dirk , Kammoun Anis , Dobbertin Thomas , Riedl Thomas , Becker Eike , Metzdorf Dirk , Schneider Daniel , Johannes Hans-Hermann , Kowalsky Wolfgang
Published: June 2003

We have prepared organic light-emitting diodes with a narrow recombination zone confined by an organic double-heterojunction structure using both polymer and small molecules (a hybrid structure). In these light-emitting diodes, we used very thin small molecule layers, down to a total thickness of 40 nm, to achieve an exponential forward characteristic. These layers were evaporated on a highly conductive layer of PEDT:PSS for a high-yield process and for good charge injection at the anode. Although no doping processes were applied during device fabrication, either at the injecting electrodes or in the Alq3 layer, the diodes attained high brightness at very low voltage, for instance, 10.000 cd/m2 at voltage of 4.7 V.
Periodical poling characteristics of congruent MgO:LiNbO3 crystals at elevated temperature
Authors: Ishizuki Hideki , Shoji Ichiro , Taira Takunori
Published: June 2003

A structure for quasi-phase matching of large cross section using 5 mol % MgO-doped LiNbO3 (MgO:LN) crystal for high-power wavelength conversion was realized. We have found that the coercive field to invert polarization of the crystal reduces drastically with elevated temperature. The coercive field reduces to 1.2 kV/mm at 250 °C, which is about 1/4 compared with that for MgO:LN at room temperature (RT) and about 1/17 of that for LN at RT. 3 mm thick periodically poled MgO:LN has been fabricated with 30 μm period.
Temperature transients and thermal properties of GaAs/AlGaAs quantum-cascade lasers
Authors: Borak A. J. , Phillips C. C. , Sirtori C.
Published: June 2003

The use of a gated interband photoluminescence technique has allowed the study of the temperature transients in the active volume of a quantum-cascade laser during pulsed operation. The active region was found to rise by ∼40 K during a 150 ns current pulse, returning to the heat-sink temperature in ∼500 ns. The measured temperature transients were fitted, using a one-dimensional heat diffusion model, giving a value of kAR=1.36±0.2 W cm−1 K−1 for the active region thermal conductivity, at 30 K. This is approximately ten times lower than literature values for bulk AlGaAs alloys of equivalent composition and has significant implications on the prospects for high-power continuous-wave device operation.
Temperature dependence of carrier mobility in Si wafers measured by infrared photocarrier radiometry
Authors: Batista Jerias , Mandelis Andreas , Shaughnessy Derrick
Published: June 2003

A recently introduced infrared photocarrier radiometry technique has been used to determine the temperature dependence of carrier mobility in Si wafers. In addition, its potential to determine simultaneously the carrier lifetime, diffusion coefficient, and surface recombination velocity is reported. This noncontact, nonintrusive, and all-optical technique relies on the detection of infrared radiation from harmonically excited free carriers (pure electronic diffusion-wave detection). Using a multiparameter fitting to a complete theory, the results showed that the lifetime increases with temperature, the diffusion coefficient decreases [D(T)∼T−1.5], and the temperature dependence of carrier mobility is μ(T)=(1.06±0.07)×109×T−2.49±0.01 cm2/V s.
Experimental evidence of polarization dependence in the optical response of opal-based photonic crystals
Authors: Galisteo-Lopez J. F. , López-Tejeira F. , Rubio S. , López C. , Sánchez-Dehesa J.
Published: June 2003

We report angle resolved reflectivity measurements showing the polarization dependence of the pseudogap in artificial opals. This kind of photonic crystals consist of silica spheres ordered in a face-centered-cubic lattice. The analyzed gap originates from the (111) family of planes. It is shown that the width of the Bragg peak observed in the reflectance spectra follows the bands determining the pseudogap, which are selectively excited according to the polarization (s or p) of the light impinging on the opal. Moreover, it is found that the coupling of light with the photonic bands occurs according to their predicted symmetry, which was assigned by arguments based on group theory.
A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C
Authors: Violin Jonathan D. , Zhang Jin , Tsien Roger Y. , Newton Alexandra C.
Published: June 2003

Signals transduced by kinases depend on the extent and duration of substrate phosphorylation. We generated genetically encoded fluorescent reporters for PKC activity that reversibly respond to stimuli activating PKC. Specifically, phosphorylation of the reporter expressed in mammalian cells causes changes in fluorescence resonance energy transfer (FRET), allowing real time imaging of phosphorylation resulting from PKC activation. Targeting of the reporter to the plasma membrane, where PKC is activated, reveals oscillatory phosphorylation in HeLa cells in response to histamine. Each oscillation in substrate phosphorylation follows a calcium oscillation with a lag of ∼10 s. Novel FRET-based reporters for PKC translocation, phosphoinositide bisphosphate conversion to IP3, and diacylglycerol show that in HeLa cells the oscillatory phosphorylations correlate with Ca2+-controlled translocation of conventional PKC to the membrane without oscillations of PLC activity or diacylglycerol. However, in MDCK cells stimulated with ATP, PLC and diacylglycerol fluctuate together with Ca2+ and phosphorylation. Thus, specificity of PKC signaling depends on the local second messenger-controlled equilibrium between kinase and phosphatase activities to result in strict calcium-controlled temporal regulation of substrate phosphorylation.
Protein Kinase C θ Affects Ca2+ Mobilization and NFAT Activation in Primary Mouse T Cells
Authors: Pfeifhofer Christa , Kofler Kurt , Gruber Thomas , Ghaffari Tabrizi Nassim , Lutz Christina , Maly Karl , Leitges Michael , Baier Gottfried
Published: June 2003

Protein kinase C (PKC)θ is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-κB. To study the physiological function of PKCθ, we used gene targeting to generate a PKCθ null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCθ-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCθ primarily abrogates NFAT transactivation. In contrast, NF-κB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca2+ mobilization. Our finding suggests that PKCθ plays a critical and nonredundant role in T cell receptor–induced NFAT activation.
Orphan Nuclear Receptor Nur77 Is Involved in Caspase-independent Macrophage Cell Death
Authors: Kim Sung Ouk , Ono Koh , Tobias Peter S. , Han Jiahuai
Published: June 2003

Activation-induced cell death in macrophages has been observed, but the mechanism remains largely unknown. Activation-induced cell death in macrophages can be independent from caspases, and the death of activated macrophages can even be triggered by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD). Here, we show that this type of macrophage death can occur in the septic mouse model and that toll-like receptor (TLR)-2 or TLR4 signaling is required in this process. We conclude that Nur77 is involved in the macrophage death because Nur77 expression correlates with cell death, and cell death is reduced significantly in Nur77-deficient macrophages. The extracellular signal–regulated kinase pathway, which is downstream of TLR2 or TLR4, and myocyte-specific enhancer binding factor 2 (MEF2) transcription factor activity, which is up-regulated by zVAD, are required for Nur77 induction and macrophage death. Reporter gene analysis suggests that Nap, Ets, Rce, and Sp1 sites in the Nur77 promoter are regulated by TLR4 signaling and that MEF2 sites in the Nur77 promoter are regulated by zVAD treatment. MEF2 transcription factors are constitutively expressed and degraded in macrophages, and zVAD increases MEF2 transcription factor activity by preventing the proteolytic cleavage and degradation of MEF2 proteins. This paper delineates the dual signaling pathways that are required for Nur77 induction in macrophages and demonstrates a role of Nur77 in caspase-independent cell death.
Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin
Authors: Falati Shahrokh , Liu Qingde , Gross Peter , Merrill-Skoloff Glenn , Chou Janet , Vandendries Erik , Celi Alessandro , Croce Kevin , Furie Barbara C. , Furie Bruce
Published: June 2003

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking.
An Alternatively Spliced Variant of CXCR3 Mediates the Inhibition of Endothelial Cell Growth Induced by IP-10, Mig, and I-TAC, and Acts as Functional Receptor for Platelet Factor 4
Authors: Lasagni Laura , Francalanci Michela , Annunziato Francesco , Lazzeri Elena , Giannini Stefano , Cosmi Lorenzo , Sagrinati Costanza , Mazzinghi Benedetta , Orlando Claudio , Maggi Enrico , Marra Fabio , Romagnani Sergio , Serio Mario , Romagnani Paola
Published: June 2003

The chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte proliferation, and act as angiostatic agents, thus inhibiting tumor growth. These multiple activities are apparently mediated by a unique G protein–coupled receptor, termed CXCR3. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including a powerful angiostatic effect, but its specific receptor is still unknown. Here, we describe a distinct, previously unrecognized receptor named CXCR3-B, derived from an alternative splicing of the CXCR3 gene that mediates the angiostatic activity of CXCR3 ligands and also acts as functional receptor for CXCL4.

Human microvascular endothelial cell line-1 (HMEC-1), transfected with either the known CXCR3 (renamed CXCR3-A) or CXCR3-B, bound CXCL9, CXCL10, and CXCL11, whereas CXCL4 showed high affinity only for CXCR3-B. Overexpression of CXCR3-A induced an increase of survival, whereas overexpression of CXCR3-B dramatically reduced DNA synthesis and up-regulated apoptotic HMEC-1 death through activation of distinct signal transduction pathways. Remarkably, primary cultures of human microvascular endothelial cells, whose growth is inhibited by CXCL9, CXCL10, CXCL11, and CXCL4, expressed CXCR3-B, but not CXCR3-A. Finally, monoclonal antibodies raised to selectively recognize CXCR3-B reacted with endothelial cells from neoplastic tissues, providing evidence that CXCR3-B is also expressed in vivo and may account for the angiostatic effects of CXC chemokines.
Human Cytomegalovirus Glycoprotein UL16 Causes Intracellular Sequestration of NKG2D Ligands, Protecting Against Natural Killer Cell Cytotoxicity
Authors: Dunn Claire , Chalupny N. Jan , Sutherland Claire L. , Dosch Stephanie , Sivakumar P.V. , Johnson David C. , Cosman David
Published: June 2003

The activating receptor, NKG2D, is expressed on a variety of immune effector cells and recognizes divergent families of major histocompatibility complex (MHC) class I–related ligands, including the MIC and ULBP proteins. Infection, stress, or transformation can induce NKG2D ligand expression, resulting in effector cell activation and killing of the ligand-expressing target cell. The human cytomegalovirus (HCMV) membrane glycoprotein, UL16, binds to three of the five known ligands for human NKG2D. UL16 is retained in the endoplasmic reticulum and cis-Golgi apparatus of cells and causes MICB to be similarly retained and stabilized within cells. Coexpression of UL16 markedly reduces cell surface levels of MICB, ULBP1, and ULBP2, and decreases susceptibility to natural killer cell–mediated cytotoxicity. Domain swapping experiments demonstrate that the transmembrane and cytoplasmic domains of UL16 are important for intracellular retention of UL16, whereas the ectodomain of UL16 participates in down-regulation of NKG2D ligands. The intracellular sequestration of NKG2D ligands by UL16 represents a novel HCMV immune evasion mechanism to add to the well-documented viral strategies directed against antigen presentation by classical MHC molecules.
Marrow Stem Cells Shift Gene Expression and Engraftment Phenotype with Cell Cycle Transit
Authors: Lambert Jean-François , Liu Meng , Colvin Gerald A. , Dooner Mark , McAuliffe Christina I. , Becker Pamela S. , Forget Bernard G. , Weissman Sherman M. , Quesenberry Peter J.
Published: June 2003

We studied the genetic and engraftment phenotype of highly purified murine hematopoietic stem cells (lineage negative, rhodamine-low, Hoechst-low) through cytokine-stimulated cell cycle. Cells were cultured in interleukin (IL)-3, IL-6, IL-11, and steel factor for 0 to 48 h and tested for engraftment capacity in a lethally irradiated murine competitive transplant model. Engraftment showed major fluctuations with nadirs at 36 and 48 h of culture and recovery during the next G1. Gene expression of quiescent (0 h) or cycling (48 h) stem cells was compared with lineage positive cells by 3′ end PCR differential display analysis. Individual PCR bands were quantified using a 0 to 9 scale and results were visually compared using color-coded matrices. We defined a set of 637 transcripts expressed in stem cells and not expressed in lineage positive cells. Gene expression analyzed at 0 and 48 h showed a major shift from “stem cell genes” being highly expressed at 0 h and turned off at 48 h, while “cell division” genes were turned on at 48 h. These observations suggest stem cell gene expression shifts through cell cycle in relation to cell cycle related alterations of stem cell phenotype. The engraftment defect is related to a major phenotypic change of the stem cell.
Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells
Authors: Wüthrich Marcel , Filutowicz Hanna I. , Warner Tom , Deepe George S. , Klein Bruce S.
Published: June 2003

Systemic fungal infections with primary and opportunistic pathogens have become increasingly common and represent a growing health menace in patients with AIDS and other immune deficiencies. T lymphocyte immunity, in particular the CD4+ Th 1 cells, is considered the main defense against these pathogens, and their absence is associated with increased susceptibility. It would seem illogical then to propose vaccinating these vulnerable patients against fungal infections. We report here that CD4+ T cells are dispensable for vaccine-induced resistance against experimental fungal pulmonary infections with two agents, Blastomyces dermatitidis an extracellular pathogen, and Histoplasma capsulatum a facultative intracellular pathogen. In the absence of T helper cells, exogenous fungal antigens activated memory CD8+ cells in a major histocompatibility complex class I–restricted manner and CD8+ T cell–derived cytokines tumor necrosis factor α, interferon γ, and granulocyte/macrophage colony-stimulating factor–mediated durable vaccine immunity. CD8+ T cells could also rely on alternate mechanisms for robust vaccine immunity, in the absence of some of these factors. Our results demonstrate an unexpected plasticity of immunity in compromised hosts at both the cellular and molecular level and point to the feasibility of developing vaccines against invasive fungal infections in patients with severe immune deficiencies, including those with few or no CD4+ T cells.
MIF Signal Transduction Initiated by Binding to CD74
Authors: Leng Lin , Metz Christine N. , Fang Yan , Xu Jing , Donnelly Seamas , Baugh John , Delohery Thomas , Chen Yibang , Mitchell Robert A. , Bucala Richard
Published: June 2003

Macrophage migration inhibitory factor (MIF) accounts for one of the first cytokine activities to have been described, and it has emerged recently to be an important regulator of innate and adaptive immunity. MIF is an upstream activator of monocytes/macrophages, and it is centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions. The protein is encoded by a unique but highly conserved gene, and X-ray crystallography studies have shown MIF to define a new protein fold and structural superfamily. Although recent work has begun to illuminate the signal transduction pathways activated by MIF, the nature of its membrane receptor has not been known. Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF. MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal–regulated kinase–1/2 MAP kinase cascade, cell proliferation, and PGE2 production. A recombinant, soluble form of CD74 binds MIF with a dissociation constant of ∼9 × 10−9 Kd, as defined by surface plasmon resonance (BIAcore analysis), and soluble CD74 inhibits MIF-mediated extracellular signal–regulated kinase activation in defined cell systems. These data provide a molecular basis for MIF's interaction with target cells and identify it as a natural ligand for CD74, which has been implicated previously in signaling and accessory functions for immune cell activation.
EIF3 p170, a Mediator of Mimosine Effect on Protein Synthesis and Cell Cycle Progression
Authors: Dong Zizheng , Zhang Jian-Ting
Published: June 2003

l-Mimosine, a plant amino acid, can reversibly block mammalian cells at late G1 phase and has been suggested to affect translation of mRNAs such as p27, the CDK inhibitor. However, the mechanism of this effect is not known. Regulation of translation generally occurs at the initiation step that, in mammalian cells, is a complex process that requires multiple eukaryotic initiation factors (eIFs) and ribosome. The effects of mimosine on initiation factors or regulators consequently will influence translation initiation. P170, a putative subunit of eIF3, has been suggested to be nonessential for eIF3 function to form preinitiation complexes and it may function as a regulator for translation of a subset of mRNAs. In this article, we tested this hypothesis and investigated whether eIF3 p170 mediates mimosine effect on mRNA translation. We found that p170 translation was dramatically reduced by mimosine due to its iron-chelating function. The decreased expression of p170 by mimosine caused diminished de novo synthesis of tyrosinated α-tubulin and elevated translation of p27 before cell cycle arrest. These observations suggest that p170 is likely an early response gene to mimosine treatment and a mediator for mimosine effect on mRNA translation. The effect of p170 on the synthesis of tyrosinated α-tubulin and p27 in a reciprocal manner also suggests that p170 functions as a regulator for mRNA translation.
Host but Not Parasite Cholesterol ControlsToxoplasmaCell Entry by Modulating Organelle Discharge
Authors: Coppens Isabelle , Joiner Keith A.
Published: June 2003

Host cell cholesterol is implicated in the entry and replication of an increasing number of intracellular microbial pathogens. Although uptake of viral particles via cholesterol-enriched caveolae is increasingly well described, the requirement of cholesterol for internalization of eukaryotic pathogens is poorly understood and is likely to be partly organism specific. We examined the role of cholesterol in active host cell invasion by the protozoan parasite Toxoplasma gondii. The parasitophorous vacuole membrane (PVM) surrounding T. gondii contains cholesterol at the time of invasion. Although cholesterol-enriched parasite apical organelles termed rhoptries discharge at the time of cell entry and contribute to PVM formation, surprisingly, rhoptry cholesterol is not necessary for this process. In contrast, host plasma membrane cholesterol is incorporated into the forming PVM during invasion, through a caveolae-independent mechanism. Unexpectedly, depleting host cell plasma membrane cholesterol blocks parasite internalization by reducing the release of rhoptry proteins that are necessary for invasion. Cholesterol back-addition into host plasma membrane reverses this inhibitory effect of depletion on parasite secretion. These data define a new mechanism by which host cholesterol specifically controls entry of an intracellular pathogen.
Deciphering the Cellular Functions of the Op18/Stathmin Family of Microtubule-Regulators by Plasma Membrane-targeted Localization
Authors: Holmfeldt Per , Brännström Kristoffer , Stenmark Sonja , Gullberg Martin
Published: June 2003

The Op18/stathmin family of microtubule regulators includes the ubiquitous cytosolic Op18/stathmin (Op18) and the neuronal, primarily Golgi-associated proteins SCG10 and RB3, which all form ternary complexes with two head-to-tail–aligned tubulin heterodimers. To understand the physiological significance of previously observed differences in ternary complex stability, we have fused each of the heterodimer-binding regions of these three proteins with the CD2 cell surface protein to generate confined plasma membrane localization of the resulting CD2 chimeras. Herein, we show that, in contrast to constitutively active CD2-Op18-tetraA, both the CD2-SCG10 and CD2-RB3 chimeras sequestered tubulin at the plasma membrane, which results in >35% reduction of cytosolic tubulin heterodimer levels and consequent delayed formation of mitotic spindles. However, all three CD2 chimeras, including the tubulin sequestration-incompetent CD2-Op18-tetraA, destabilize interphase microtubules. Given that microtubules are in extensive contact with the plasma membrane during interphase, but not during mitosis, these findings indicate that Op18-like proteins have the potential to destabilize microtubules by both sequestration and direct interaction with microtubules. However, the differences in tubulin binding observed in cells also indicate conceptual differences between the functions of low-abundance neural family members, which will accumulate tubulin at specific cellular compartments, and the abundant cytosolic Op18 protein, which will not.
The Association between Integrin-associated Protein and SHPS-1 Regulates Insulin-like Growth Factor-I Receptor Signaling in Vascular Smooth Muscle Cells
Authors: Maile Laura A. , Badley-Clarke Jane , Clemmons David R.
Published: June 2003

Growth factor signaling is usually analyzed in isolation without considering the effect of ligand occupancy of transmembrane proteins other than the growth factor receptors themselves. In smooth muscle cells, the transmembrane protein Src homology 2 domain containing protein tyrosine phosphatase substrate-1 (SHPS-1) has been shown to be an important regulator of insulin-like growth factor-I (IGF-I) signaling. SHPS-1 is phosphorylated in response to IGF-I, leading to recruitment of Src homology 2 domain tyrosine phosphatase (SHP-2). Subsequently, SHP-2 is transferred to IGF-I receptor and regulates the duration of IGF-I receptor phosphorylation. Whether ligand occupancy of SHPS-1 influences SHPS-1 phosphorylation or SHP-2 recruitment, thereby altering growth factor signaling, is unknown. Previous studies have shown that integrin associated protein (IAP) associates with SHPS-1. We undertook these studies to determine whether this interaction controlled SHPS-1 phosphorylation and/or SHP-2 recruitment and thereby regulated IGF-I signaling. Disruption of IAP-SHPS-1 binding, by using an IAP monoclonal antibody or cells expressing mutant forms of IAP that did not bind to SHPS-1, inhibited IGF-I–stimulated SHPS-1 phosphorylation and SHP-2 recruitment. This was associated with a lack of SHP-2 transfer to IGF-I receptor and sustained receptor phosphorylation. This resulted in an inability of IGF-I to stimulate sustained mitogen-activated protein kinase activation, cell proliferation, and cell migration. The effect was specific for IGF-I because disruption of the IAP–SHPS-1 interaction had no effect on platelet-derived growth factor-stimulated SHPS-1 phosphorylation or cell migration. In summary, our results show that 1) ligand occupancy of SHPS-1 is a key determinant of its ability to be phosphorylated after IGF-I stimulation, and 2) the interaction between IAP and SHPS-1 is an important regulator of IGF-I signaling because disruption of the results in impaired SHP-2 recruitment and subsequent inhibition of IGF-I–stimulated cell proliferation and migration.
A genetic system for the rapid isolation of aromatic-ring-hydroxylating dioxygenase activities
Authors: Kahl Silke , Hofer Bernd
Published: June 2003

Aromatic-ring-hydroxylating dioxygenases (ARHDOs) are key enzymes in the aerobic bacterial metabolism of aromatic compounds. They are of biotechnological importance as they function as biocatalysts in the stereospecific synthesis of chiral synthons and the degradation of aromatic pollutants. This report describes the development and validation of a system for the rapid isolation and characterization of specific ARHDO activities. The system is based on the identification of ARHDO gene segments that encode the enzymes' major functional determinants, on consensus primers for the direct amplification of such partial genes and on a ‘recipient’ ARHDO gene cluster for the insertion of the amplified segments. Previously, it has been shown that neither the N- nor the C-terminal portions but only the core region of the large or α-subunit of a class II ARHDO significantly influence substrate and product spectra. On the basis of these observations, consensus primers were designed for the amplification of the gene segment encoding the catalytic core of the large subunit. These primers were tested on 11 bacterial isolates known to metabolize aromatic compounds. In 10 cases, a gene fragment of expected length was amplified. DNA sequencing confirmed similarity to ARHDO α-subunit gene cores. The heterologously well-expressible bphA gene cluster of Burkholderia sp. strain LB400 was modified to facilitate the in-frame insertion of amplified segments. It was used successfully to express the resulting hybrid gene clusters and to form catalytically active chimaeric ARHDOs. The metabolic properties of these enzymes differed significantly from each other and from the parental ARHDO of strain LB400. These results indicate that the system described here can be used to rapidly isolate and functionally characterize ARHDO activities, starting from isolated strains, mixtures of organisms or samples of nucleic acids. Applications of the system range from the recruitment of novel ARHDO activities to an improved characterization of natural ARHDO diversity.