bluuebunny/crossref_metadata_2025 huggingface dataset:
Predication of second-order optical nonlinearity of [(Bu2tIm)AuX] (X=halogen) using time-dependent density-functional theory combined with sum-over-states method
Authors: Yang Guochun , Su Zhongmin , Qin Chunsheng , Zhao Yahui
Published: September 2005

The dipole polarizability and second-order polarizability of recently synthesized (1,3-di-ter-butylimidazol-2-ylidine) gold complexes [(Bu2tIm)AuX] (X=halogen) were investigated by using time-dependent density-functional theory combined with sum-over-states method. We have discovered that these complexes possess remarkably larger molecular second-order polarizability compared with the organometallic and organic complexes. The value of the second-order polarizability increases in the order of F<Cl<Br<I. The analysis of the molecular orbital suggests that the charge transfer from halogen atom to the carbene ligand plays the key role in nonlinear optical response of gold complexes. The gold of these complexes is a bridge of charge transfer, unlike other organometallic complexes, the metal center may be a strong donor or acceptor. These complexes have a possibility to be excellent second-order nonlinear optical materials from the standpoint of transparency, relatively large β values and relatively small dispersion behaviors.
Br
2
elimination in 248-nm photolysis of CF2Br2 probed by using cavity ring-down absorption spectroscopy
Authors: Hsu Ching-Yi , Huang Hong-Yi , Lin King-Chuen
Published: September 2005

By using cavity ring-down absorption spectroscopy technique, we have observed the channel of Br2 molecular elimination following photodissociation of CF2Br2 at 248 nm. A tunable laser beam, which is crossed perpendicular to the photolyzing laser beam in a ring-down cell, is used to probe the Br2 fragment in the BΠou+3-XΣg+1 transition. The vibrational population is obtained in a nascent state, despite ring-down time as long as 500–1000 ns. The population ratio of Br2(v=1)∕Br2(v=0) is determined to be 0.4±0.2, slightly larger than the value of 0.22 evaluated by Boltzmann distribution at room temperature. The quantum yield of the Br2 elimination reaction is also measured to be 0.04±0.01. This work provides direct evidence to support molecular elimination occurring in the CF2Br2 photodissociation and proposes a plausible pathway with the aid of ab initio potential-energy calculations. CF2Br2 is excited probably to the B11 and B23 states at 248 nm. As the C–Br bond is elongated upon excitation, the coupling of the A′1(B11) state to the high vibrational levels of the ground state X̃A′1(A11) may be enhanced to facilitate the process of internal conversion. After transition, the highly vibrationally excited CF2Br2 feasibly surpasses a transition barrier prior to decomposition. According to the ab initio calculations, the transition state structure tends to correlate with the intermediate state CF2Br+Br(CF2Br⋯Br) and the products CF2+Br2. A sequential photodissociation pathway is thus favored. That is, a single C–Br bond breaks, and then the free-Br atom moves to form a Br–Br bond, followed by the Br2 elimination. The formed Br–Br bond distance in the transition state tends to approach equilibrium such that the Br2 fragment may be populated in cold vibrational distribution. Observation of a small vibrational population ratio of Br2(v=1)∕Br2(v=0) agrees with the proposed mechanism.
Microstructure and ferroelectric properties of MnO2-doped bismuth-layer (Ca,Sr)Bi4Ti4O15 ceramics
Authors: Li Gurong , Zheng Liaoying , Yin Qingrui , Jiang Bei , Cao Wenwu
Published: September 2005

We have studied the microstructures and ferroelectric properties of MnO2-doped bismuth-layered (Ca,Sr)Bi4Ti4O15 (CSBTM). The piezoelectric coefficient, dielectric loss, mechanical quality factor, and the P-E hysteresis loop measurements indicate that Mn ions entered both the A and B sites of the pseudoperovskite-layered structure, creating “soft” and “hard” doping effects simultaneously. Scanning electron microscopy and energy dispersion spectroscopy showed that the platelike grains in CSBTM ceramics become larger with the increase of MnO2 additive, and Mn ions are found inside the grains as well as in the grain boundaries. The lattice parameter, room-temperature dielectric constant, and the Curie temperature do not vary with MnO2 additive. We conclude that the Mn3+ ions play a critical role in the effects of soft and hard behaviors since it can enter both the A and B sites of the perovskite structure.
Early stages of soldering reactions
Authors: Lord R. A. , Umantsev A.
Published: September 2005

An experiment on the early stages of intermetallic compound layer growth during soldering and its theoretical analysis were conducted with the intent to study the controlling factors of the process. An experimental technique based on fast dipping and pulling of a copper coupon in liquid solder followed by optical microscopy allowed the authors to study the temporal behavior of the sample on a single micrograph. The technique should be of value for different areas of metallurgy because many experiments on crystallization may be described as the growth of a layer of intermediate phase. Comparison of the experimental results with the theoretical calculations allowed one to identify the kinetics of dissolution as the rate-controlling mechanism on the early stages and measure the kinetic coefficient of dissolution. A popular model of intermetallic compound layer structure coarsening is discussed.
Size distribution of sputtered particles from Au nanoislands due to MeV self-ion bombardment
Authors: Satpati B. , Ghatak J. , Satyam P. V. , Dev B. N.
Published: September 2005

Nanoisland gold films, deposited by vacuum evaporation of gold onto Si(100) substrates, were irradiated with 1.5MeV Au2+ ions up to a fluence of 5×1014ionscm−2 and at incidence angles up to 60° with respect to the surface normal. The sputtered particles were collected on carbon-coated grids (catcher grid) during ion irradiation and were analyzed with transmission electron microscopy and Rutherford backscattering spectrometry. The average sputtered particle size and the areal coverage are determined from transmission electron microscopy measurements, whereas the amount of gold on the substrate is found by Rutherford backscattering spectrometry. The size distributions of larger particles (number of atoms/particle, n⩾1000) show an inverse power law with an exponent of ∼−1 in broad agreement with a molecular-dynamics simulation of ion impact on cluster targets.
Liquid adhesion to an ultrasonically vibrating end surface
Authors: Tamura S. , Tsunekawa Y. , Okumiya M. , Furukawa Y.
Published: September 2005

There exists a unique phenomenon of a large amount of liquid adhering to an ultrasonically vibrating end surface in the horizontal plane. The droplet assumes characteristic shapes that depend on the amplitude of vibration. In order to examine the mechanism of this phenomenon, the effects of the intrinsic surface tension of the adhering liquid and distribution of the intensity of the acoustic radiation pressure on the adhering droplet were investigated. Based on the experimental results, a dynamic balance model of the adhering droplet was constructed considering the balance of weight, surface tension, and acoustic radiation pressure. The calculated shape of the adhering droplet using this model is in good agreement with that observed. The mechanism that allows a large amount of a liquid to adhere to the horizontal end surface is discussed, focusing on the distribution of the acoustic radiation pressure in the droplet.
Field dependence of micromagnetic domain patterns in MnAs films
Authors: Engel-Herbert R. , Hesjedal T. , Mohanty J. , Schaadt D. M. , Ploog K. H.
Published: September 2005

We have studied the domain behavior of submicrometer wide ferromagnetic stripes by magnetic force microscopy (MFM) in the presence of an in situ magnetic field. MFM images in the demagnetized state show alternatingly magnetized domains fully extended across the stripe. Moreover, domain structures are found to exhibit a substructure across the stripe. Increasing fields drive out the domain walls of the complex domains first, leaving the alternating domains behind. The remaining magnetization process aligns increasing parts of the domains along the field direction by gradually shrinking the width of oppositely magnetized domains rather than by flipping larger areas at once. Micromagnetic simulations confirm the observed behavior. The simulations reveal that flipping of the domains occurs only when a magnetic pinning center is involved.
Pattern formation in an array of magnetic nanoscale rods mimics magnetic-dipole interaction-driven spinodal decomposition
Authors: Wolf H. , Birringer R.
Published: September 2005

Magnetic-field-assisted self-assembly of magnetic-dipole moment carrying aerosol-grown iron nanoparticles on a nonmagnetic substrate results in the formation of magnetic nanoscale rods and bundles thereof. The magnetic dipolar interaction between the bundles essentially drives the formation of regular patterns of bundle density modulations in the two-dimensional array of elastically deformable magnetic rods. This pattern formation is shown to belong to the class of physical systems undergoing spinodal decomposition. Possible applications for dipolar magnetic nanorods in the fields of perpendicular storage media and ferrofluids are highlighted. A giant magnetoviscous effect is expected.
Double sublimation system to deposit molecules from solid organic compounds onto a cryogenic substrate: Thymine on solid argon
Authors: Levesque P. L. , Michaud M. , Sanche L.
Published: September 2005

We report on the design, operation, and performance of a double sublimation system for the deposition of a submonolayer up to a few layers of a low-vapor pressure molecular solid compound onto a cryogenic substrate. The system consists of a primary oven (i.e., crucible type) to degas and first sublimate the compound onto the tip of a secondary oven (i.e., finger type), which is then used to transport the purified compound inside an analysis chamber and sublimate it just in front of the cryogenic substrate. The latter is kept at exactly the same position all the time, which is essential for experiments sensitive to target position. Besides, the negligible radiant heat transfer from the tip of the secondary oven allows operation in the presence of a cryogenic substrate consisting of an inert gas solid. The overall performance of the system is studied by EEL spectroscopy for thymine deposited onto a multilayer film of Ar used as an inert cryogenic substrate.
Reflectron velocity map ion imaging
Authors: Leskiw Brian D. , Kim Myung Hwa , Hall Gregory E. , Suits Arthur G.
Published: September 2005

We report the first demonstration of velocity map ion imaging in a reflectron configuration. Under these conditions, the velocity-resolving capabilities associated with velocity map ion imaging are achieved simultaneously with long flight times and the high mass resolution characteristic of reflectron time-of-flight mass spectrometers. The photodissociation of OCS at 230 nm has been used to characterize the velocity-focusing performance of the instrument. The reflectron geometry provides an increased magnification factor over conventional velocity map ion imaging.
Drift mobility in 4H-SiC Schottky diodes
Authors: La Via F. , Galvagno G. , Roccaforte F. , Ruggiero A. , Calcagno L.
Published: September 2005

In this work, the temperature dependence of the mobility along the c axis in 4H-SiC was determined from the current voltage (I-V) characteristics of Schottky diodes in the temperature range 80–700 K. The procedure used series resistance measurements in Schottky diodes for extracting the mobility values in the epitaxial layer. For a dopant concentration of 1.2×1016cm−3, at room temperature, a mobility value of 724cm2∕(Vs) was found, which decreased to 48.6cm2∕(Vs) at 700 K. In the temperature range 200–700 K, a dependence of the mobility as T−3 was determined.
Self-organized nanostripe arrays on ZnO (10-10) surfaces formed during laser molecular-beam-epitaxy growth
Authors: Matsui Hiroaki , Tabata Hitoshi
Published: September 2005

Nanostripe arrays with high density in the orders of 10−5cm−1 were naturally formed on ZnO (10-10) surfaces during laser molecular-beam-epitaxy (laser-MBE) growth. The nanostripe arrays were elongated above 5μm with a few branches along the [0001] direction. Transmittance electron microscopy showed that the nanostripe arrays were triangular-shaped in the cross section and two side bonding facets were composed of high-index [(31-40) and (4-1-30)] planes. The growth origin of the nanostripe arrays was derived from a step-faceting mechanism and nonthermal equilibrium growth by laser-MBE. The step faceting could be controlled by various growth conditions relating to the surface diffusion length of the ablated active species. It was found that the highly anisotropic surfaces dramatically affected electron transport of the ZnO (10-10) layers with Hall mobility parallel to the nanostripe edges more than two orders of magnitude larger than that perpendicular to the edges.
Fracture toughness of nanostructured silicon carbide
Authors: Ippolito M. , Mattoni A. , Colombo L. , Cleri F.
Published: September 2005

By using atomistic simulations, we derive a constitutive equation for a microfractured β-SiC matrix containing hard or soft inclusions. The proposed equation is shown to follow the Eshelby theory for elastic inclusions, and appears to hold for any crack tip-inclusion distance and for a wide range of values of matrix-inclusion elastic mismatch. A comparison of the atomistic results with existing continuum elasticity models points out the weaknesses of some commonly adopted simplifying assumptions.
High-contrast top-emitting organic light-emitting devices for active-matrix displays
Authors: Yang Chih-Jen , Lin Chun-Liang , Wu Chung-Chih , Yeh Yung-Hui , Cheng Chun-Cheng , Kuo Yen-Hsun , Chen Tai-Hong
Published: September 2005

Unlike previous high-contrast devices that all involve inserting extra layer(s) with optical purposes (e.g., absorption and interference) into the active region of devices, in this-letter we report a high-contrast top-emitting organic light-emitting device (OLED) that utilizes only optical characteristics of electrodes and anti-reflection coatings deposited outside the active region, thus reducing the complexity of devices. Furthermore, the device has an inherent microcavity which is beneficial to electroluminescence efficiency. The devices are readily compatible with the processing of active-matrix backplanes, and active-matrix OLED displays incorporating such high-contrast top-emitting devices were demonstrated to have improved readability under a strong lighting environment.
Smart membranes: A physical model for a circadian behavior
Authors: Rodríguez R. , Castaño V. M.
Published: September 2005

Synthetic “smart” membranes, able to adjust their pore sizes, from 1to50μm, depending on the physical and/or chemical environment, are presented. Their oscillatory behavior, resembling that of many living systems, is accurately reproduced by a model based on the two competing phenomena in the membrane: elastic forces and steric interactions.
Integration of ferroelectric lead titanate nanoislands for direct hysteresis measurements
Authors: Clemens S. , Schneller T. , Waser R. , Rüdiger A. , Peter F. , Kronholz S. , Schmitz T. , Tiedke S.
Published: September 2005

We report on the integration of fully functional ferroelectric PbTiO3 nanostructures of typically less than 100nm lateral extension into a low-k dielectric hydrogen silsesquioxane film. Chemical mechanical polishing of the dielectric layer down to an overall thickness below the nanoparticles height exposes the structures. After confirmation of the piezoelectricity of individual embedded grains, gold electrode pads are deposited to characterize several of these grains in parallel. Evidence of ferroelectric switching is observed and discussed within an equivalent circuit model. This paves the way to a better integration and statistical analysis of ferroelectric nanostructures.
High-quality GaNAs∕GaAs quantum wells with light emission up to 1.44μm grown by molecular-beam epitaxy
Authors: Wang S. M. , Gu Q. F. , Wei Y. Q. , Sadeghi M. , Larsson A. , Zhao Q. X. , Wang X. D. , Ma C. H. , Xing Z. G.
Published: September 2005

High-quality GaNAs∕GaAs quantum wells with high substitutional N concentrations, grown by molecular-beam epitaxy, are demonstrated using a reduced growth rate in a range of 0.125–1μm∕h. No phase separation is observed and the GaNAs well thickness is limited by the critical thickness. Strong room-temperature photoluminescence with a record long wavelength of 1.44μm is obtained from an 18-nm-thick GaN0.06As0.94∕GaAs quantum well.
Stabilization effect in ferroelectric materials during aging in ferroelectric state
Authors: Sun Dazhi , Ren Xiaobing , Otsuka Kazuhiro
Published: September 2005

We report that aging in ferroelectric state results in an increase of reverse transition temperature Tf in both BaTiO3 single crystal and Pb0.84La0.16Ti0.96O3 polycrystal. This indicates that the ferroelectric phase is gradually stabilized during aging below Curie temperature. The evolution of the stabilization with aging time in these two different systems obeys the same kinetic function, but with different relaxation time. This indicates that the stabilization effect of the two systems stems from a common origin. We suggest that the stabilization is due to a short-range ordering of point defects, driven by a symmetry-conforming tendency of point defects.
Technique for increasing dynamic range of space-borne ion composition instruments
Authors: Burch J. L. , Miller G. P. , De Los Santos A. , Pollock C. J. , Pope S. E. , Valek P. W. , Young D. T.
Published: September 2005

The dynamic range of ion composition spectrometers is limited by several factors, including saturation of particle counters and spillover of signals from highly dominant species into channels tuned to minor species. Instruments designed for composition measurements of hot plasmas in space can suffer greatly from both of these problems because of the wide energy range required and the wide disparity in fluxes encountered in various regions of interest. In order to detect minor ions in regions of very weak fluxes, geometry factors need to be as large as possible within the mass and volume resources available. As a result, problems with saturation by the dominant fluxes and spillover to minor-ion channels in plasma regions with intense fluxes become especially acute. This article reports on a technique for solving the dynamic-range problem in the few eV to several keV energy/charge range that is of central importance for space physics research where the dominant ion is of low mass/charge (typically H+), and the minor ions are of higher mass/charge (typically O+). The technique involves employing a radio-frequency modulation of the deflection electric field in the back section of an electrostatic analyzer in a time-of-flight instrument. This technique is shown to reduce H+ counts by a controllable amount of up to factors of 1000 while reducing O+ counts by only a few percent that can be calibrated.
Exclusive-OR gate using a two-input single-electron transistor in single-wall carbon nanotubes
Authors: Tsuya D. , Suzuki M. , Aoyagi Y. , Ishibashi K.
Published: September 2005

We demonstrated a two-input exclusive-OR (XOR) gate using a single-electron transistor with two similar side gates in single-wall carbon nanotubes. Coulomb peaks were adjusted to have a half phase difference by a high input voltage to one of the two gates. The output current was in a low level when the same voltages, high or low, were applied to both gates, while it was in a high level when different voltages were applied to each gate, a XOR behavior. The present device operated up to ∼30K.
Longitudinal-mode competition induced instabilities of Cr4+,Nd3+:Y3Al5O12 self-Q-switched two-mode laser
Authors: Dong Jun , Ueda Ken-ichi
Published: September 2005

Stable single-longitudinal-mode laser pulses and instability of two-longitudinal-mode oscillation due to the spatial hole-burning effect were observed experimentally in a laser-diode pumped microchip Cr4+,Nd3+:Y3Al5O12 self-Q-switched laser. We modified the multimode rate equations by including the spatial hole-burning effect in the active medium and the nonlinear absorption of the saturable absorber. The numerical simulations of the mode-competition dynamics of two-mode laser are in good agreement with the experimental data. Instability induced by the mode-competition dynamics was investigated by the evolution of the inversion population and the bleaching and recovery of the inversion population of the saturable absorber.
Making Embeddedness Work: Social Practice Institutions in Foreign Consulting Markets
Authors: Glückler Johannes
Published: September 2005

This paper develops conceptual and empirical evidence for the importance of social practice institutions in the internationalisation process of management-consulting firms. Personal trust and reputation rather than price are examined as key mechanisms of foreign market entry and penetration. Empirical case studies in London, Frankfurt, and Madrid produce three findings. First, enduring client relations and client referrals facilitated most foreign firm entries and the majority of local client acquisition. Second, interview findings imply a critical assessment and reconceptualisation of trust and reputation. Empirically, goodwill trust and networked reputation are substantiated as particularly important transaction mechanisms. Third, a triangulation of interview and survey data reveals a causal relation between trust and reputation that enhanced a cumulative growth of social networks within the new host markets. This research points to the importance of social practice institutions for economic organisation and exchange across geographic distance.
Apical role for BRG1 in cytokine-induced promoter assembly
Authors: Ni Zuyao , Karaskov Elizabeth , Yu Tao , Callaghan Steven M. , Der Sandy , Park David S. , Xu Zhaodong , Pattenden Samantha G. , Bremner Rod
Published: September 2005

IFN-γ induction of the CIITA (class II transactivator) promoter (pIV) requires Brahma-related gene 1 (BRG1), a chromatin-remodeling enzyme. However, the events that lead to pIV activation are only partially understood, and the point at which BRG1 acts is unknown. The first IFN-γ-induced event triggers nuclear translocation of STAT1 (signal transducer and activator of transcription 1), which binds IFN-γ-responsive promoters. BRG1 is recruited after activator binding at several other inducible loci, and STAT family members are known to bind BRG1, suggesting that BRG1 might act downstream of STAT1. Here, we delineate a comprehensive view of factor assembly and detailed histone modifications at pIV and show that all events, even STAT1 binding, require BRG1 at CIITA pIV and other IFN-γ target promoters. Recruitment of IFN-stimulated gene factor-3 (ISGF3) [STAT1/STAT2/IFN regulatory factor 9 (IRF9)] to several IFN-α-responsive promoters is also BRG1-dependent. In contrast, constitutive BRG1 association at IFN targets is STAT1-independent. Furthermore, BRG1 is required for IFN-induced restriction enzyme and DNase I accessibility at promoters. Thus, BRG1 has an apical role in cytokine-induced promoter assembly, acting upstream of STAT complexes at multiple IFN target loci.
The players in a mutualistic symbiosis: Insects, bacteria, viruses, and virulence genes
Authors: Moran Nancy A. , Degnan Patrick H. , Santos Scott R. , Dunbar Helen E. , Ochman Howard
Published: September 2005

Aphids maintain mutualistic symbioses involving consortia of coinherited organisms. All possess a primary endosymbiont,
Buchnera
, which compensates for dietary deficiencies; many also contain secondary symbionts, such as
Hamiltonella defensa
, which confers defense against natural enemies. Genome sequences of uncultivable secondary symbionts have been refractory to analysis due to the difficulties of isolating adequate DNA samples. By amplifying DNA from hemolymph of infected pea aphids, we obtained a set of genomic sequences of
H. defensa
and an associated bacteriophage.
H. defensa
harbors two type III secretion systems, related to those that mediate host cell entry by enteric pathogens. The phage, called APSE-2, is a close relative of the previously sequenced APSE-1 but contains intact homologs of the gene encoding cytolethal distending toxin (
cdtB
), which interrupts the eukaryotic cell cycle and which is known from a variety of mammalian pathogens. The
cdtB
homolog is highly expressed, and its genomic position corresponds to that of a homolog of
stx
(encoding Shiga-toxin) within APSE-1. APSE-2 genomes were consistently abundant in infected pea aphids, and related phages were found in all tested isolates of
H. defensa
, from numerous insect species. Based on their ubiquity and abundance, these phages appear to be an obligate component of the
H. defensa
life cycle. We propose that, in these mutualistic symbionts, phage-borne toxin genes provide defense to the aphid host and are a basis for the observed protection against eukaryotic parasites.
Multisite protein phosphorylation makes a good threshold but can be a poor switch
Authors: Gunawardena Jeremy
Published: September 2005

Phosphorylation and dephosphorylation play a fundamental role in eukaryotic signaling. Some 30% of proteins are phosphorylated at any time, many on multiple sites, raising the question of how the cellular phosphorylation state is regulated. Previous work for one and two phosphorylation sites has revealed mechanisms, such as distributive phosphorylation, for switch-like regulation of maximally phosphorylated phosphoforms. These insights have led to the influential view that more phosphorylation sites leads to steeper switching, as proposed for substrates like cyclin E and the cyclin-dependent kinase inhibitor Sic1. An analytical study of the ordered distributive case reveals a more complex story. Multisite phosphorylation creates an efficient threshold: The proportion of maximally phosphorylated substrate is maintained close to 0 when the ratio of kinase to phosphatase activity lies below a suitable threshold, and this threshold increases with increasing numbers of sites,
n
. However, above the threshold, the response may not always abruptly switch between 0 and 1, as would be the case for an efficient switch, but may increase in a gradual manner, which becomes more hyperbolic with increasing
n
. Abrupt switching cannot be attributed merely to
n
being large. We point out that conventional measures of ultrasensitivity must be modified to discriminate between thresholding and switching; we discuss additional factors that influence switching efficiency and suggest new directions for experimental investigation.
Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation
in utero
Authors: Frattini Annalisa , Blair Harry C. , Sacco Maria Grazia , Cerisoli Francesco , Faggioli Francesca , Catò Enrica Mira , Pangrazio Alessandra , Musio Antonio , Rucci Francesca , Sobacchi Cristina , Sharrow Allison C. , Kalla Sara E. , Bruzzone Maria Grazia , Colombo Roberto , Magli Maria Cristina , Vezzoni Paolo , Villa Anna
Published: September 2005

Autosomal recessive osteopetrosis (ARO) is a paradigm for genetic diseases that cause severe, often irreversible, defects before birth. In ARO, osteoclasts cannot remove mineralized cartilage, bone marrow is severely reduced, and bone cannot be remodeled for growth. More than 50% of the patients show defects in the osteoclastic vacuolar-proton-pump subunit, ATP6a3. We treated ATP6a3-deficient mice by
in utero
heterologous hematopoietic stem cell (HSC) transplant from outbred GFP transgenic mice. Dramatic phenotype rescue by GFP osteoclasts was obtained with engraftment, which was observed in most cases. Engraftment survived for variable periods. Recipients were not immunosuppressed, and graft-versus-host disease was not observed in all pups born after
in utero
treatment. Thus, differentiation of unmatched HSC transplanted
in utero
is sufficient to prevent fatal defects in ARO and may prevent complications of ARO unresponsive to conventional bone marrow transplantation. The presence of defective cells is not a barrier to the rescue of the phenotype by donor HSC.
A proof of a generalization of Deligne’s conjecture
Authors: Varshavsky Yakov
Published: September 2005

The goal of this paper is to give a simple proof of Deligne’s conjecture on the Lefschetz trace formula (proven by Fujiwara) and to generalize it to the situation appearing in the forthcoming joint paper with D. Kazhdan. Our proof holds in the realm of ordinary algebraic geometry and does not use rigid geometry.
Rab15 Effector Protein: A Novel Protein for Receptor Recycling from the Endocytic Recycling Compartment
Authors: Strick David J. , Elferink Lisa A.
Published: September 2005

Sorting endosomes and the endocytic recycling compartment are critical intracellular stores for the rapid recycling of internalized membrane receptors to the cell surface in multiple cell types. However, the molecular mechanisms distinguishing fast receptor recycling from sorting endosomes and slow receptor recycling from the endocytic recycling compartment remain poorly understood. We previously reported that Rab15 differentially regulates transferrin receptor trafficking through sorting endosomes and the endocytic recycling compartment, suggesting a role for distinct Rab15-effector interactions at these endocytic compartments. In this study, we identified the novel protein Rab15 effector protein (REP15) as a binding partner for Rab15-GTP. REP15 is compartment specific, colocalizing with Rab15 and Rab11 on the endocytic recycling compartment but not with Rab15, Rab4, or early endosome antigen 1 on sorting endosomes. REP15 interacts directly with Rab15-GTP but not with Rab5 or Rab11. Consistent with its localization, REP15 overexpression and small interfering RNA-mediated depletion inhibited transferrin receptor recycling from the endocytic recycling compartment, without affecting receptor entry into or recycling from sorting endosomes. Our data identify REP15 as a compartment-specific protein for receptor recycling from the endocytic recycling compartment, highlighting that the rapid and slow modes of transferrin receptor recycling are mechanistically distinct pathways.
Zonula Occludens-1 Alters Connexin43 Gap Junction Size and Organization by Influencing Channel Accretion
Authors: Hunter Andrew W. , Barker Ralph J. , Zhu Ching , Gourdie Robert G.
Published: September 2005

Regulation of gap junction (GJ) organization is critical for proper function of excitable tissues such as heart and brain, yet mechanisms that govern the dynamic patterning of GJs remain poorly defined. Here, we show that zonula occludens (ZO)-1 localizes preferentially to the periphery of connexin43 (Cx43) GJ plaques. Blockade of the PDS95/dlg/ZO-1 (PDZ)-mediated interaction between ZO-1 and Cx43, by genetic tagging of Cx43 or by a membrane-permeable peptide inhibitor that contains the Cx43 PDZ-binding domain, led to a reduction of peripherally associated ZO-1 accompanied by a significant increase in plaque size. Biochemical data indicate that the size increase was due to unregulated accumulation of gap junctional channels from nonjunctional pools, rather than to increased protein expression or decreased turnover. Coexpression of native Cx43 fully rescued the aberrant tagged-connexin phenotype, but only if channels were composed predominately of untagged connexin. Confocal image analysis revealed that, subsequent to GJ nucleation, ZO-1 association with Cx43 GJs is independent of plaque size. We propose that ZO-1 controls the rate of Cx43 channel accretion at GJ peripheries, which, in conjunction with the rate of GJ turnover, regulates GJ size and distribution.
A note on using permutation-based false discovery rate estimates to compare different analysis methods for microarray data
Authors: Xie Yang , Pan Wei , Khodursky Arkady B.
Published: September 2005

Motivation: False discovery rate (FDR) is defined as the expected percentage of false positives among all the claimed positives. In practice, with the true FDR unknown, an estimated FDR can serve as a criterion to evaluate the performance of various statistical methods under the condition that the estimated FDR approximates the true FDR well, or at least, it does not improperly favor or disfavor any particular method. Permutation methods have become popular to estimate FDR in genomic studies. The purpose of this paper is 2-fold. First, we investigate theoretically and empirically whether the standard permutation-based FDR estimator is biased, and if so, whether the bias inappropriately favors or disfavors any method. Second, we propose a simple modification of the standard permutation to yield a better FDR estimator, which can in turn serve as a more fair criterion to evaluate various statistical methods.

Results: Both simulated and real data examples are used for illustration and comparison. Three commonly used test statistics, the sample mean, SAM statistic and Student's t-statistic, are considered. The results show that the standard permutation method overestimates FDR. The overestimation is the most severe for the sample mean statistic while the least for the t-statistic with the SAM-statistic lying between the two extremes, suggesting that one has to be cautious when using the standard permutation-based FDR estimates to evaluate various statistical methods. In addition, our proposed FDR estimation method is simple and outperforms the standard method.

Contact:  yangxie@biostat.umn.ed
Profile-based direct kernels for remote homology detection and fold recognition
Authors: Rangwala Huzefa , Karypis George
Published: September 2005

Motivation: Protein remote homology detection is a central problem in computational biology. Supervised learning algorithms based on support vector machines are currently one of the most effective methods for remote homology detection. The performance of these methods depends on how the protein sequences are modeled and on the method used to compute the kernel function between them.

Results: We introduce two classes of kernel functions that are constructed by combining sequence profiles with new and existing approaches for determining the similarity between pairs of protein sequences. These kernels are constructed directly from these explicit protein similarity measures and employ effective profile-to-profile scoring schemes for measuring the similarity between pairs of proteins. Experiments with remote homology detection and fold recognition problems show that these kernels are capable of producing results that are substantially better than those produced by all of the existing state-of-the-art SVM-based methods. In addition, the experiments show that these kernels, even when used in the absence of profiles, produce results that are better than those produced by existing non-profile-based schemes.

Availability: The programs for computing the various kernel functions are available on request from the authors.

Contact:  karypis@cs.umn.edu
Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues
Authors: Wachi Shinichiro , Yoneda Ken , Wu Reen
Published: September 2005

Motivation: Global protein interaction network (interactome) analysis provides an effective way to understand the relationships between genes. Through this approach, it was demonstrated that the essential genes in yeast tend to be highly connected as well as connected to other highly connected genes. This is in contrast to the genes that are not essential, which share neither of these properties. Using a similar interactome-transcriptome approach, the topological features in the interactome of differentially expressed genes in lung squamous cancer tissues are assessed.

Results: This analysis reveals that the genes that are differentially elevated, as obtained from the microarray gene profiling data, in cancer are well connected, whereas the suppressed genes and randomly selected ones are less so. These results support the notion that a topological analysis of cancer genes using protein interaction data will allow the placement of the list of genes, often of the disparate nature, into the global, systematic context of the cell. The result of this type of analysis may provide the rationale for therapeutic targets in cancer treatment.

Contact: swachi@ucdavis.edu

Supplementary information: Supplementary data for this paper are available on Bioinformatics online.
HapSim: a simulation tool for generating haplotype data with pre-specified allele frequencies and LD coefficients
Authors: Montana Giovanni
Published: September 2005

We have developed a simulation tool HapSim for the generation of haplotype data. The simulated haplotypes are such that their allele frequencies and linkage disequilibrium coefficients match exactly those estimated in a real sample.

Availability: The program is available as an R package and can be downloaded from

Contact:  g.montana@imperial.ac.uk
First Human Exposure of Org 25969, a Novel Agent to Reverse the Action of Rocuronium Bromide
Authors: Gijsenbergh Francois , Ramael Steven , Houwing Natalie , van Iersel Thijs
Published: September 2005

Background

Acetylcholinesterase inhibitors are widely used for the reversal of neuromuscular blocking agents. However, acetylcholinesterase inhibitors have several side effects and are not effective during profound block. Org 25969 is a modified gamma-cyclodextrin that encapsulates the neuromuscular blocking agent, rocuronium bromide (Esmeron/Zemuron, NV Organon, Oss, The Netherlands), forming a tightly bound complex with an association constant of approximately 10 m. Chemical encapsulation of rocuronium promotes dissociation of rocuronium from the acetylcholine receptor, thereby reversing the neuromuscular block without the side effects associated with acetylcholinesterase inhibitors.

Methods

Twenty-nine healthy male volunteers were enrolled to investigate the safety, pharmacokinetics, and efficacy of Org 25969. In part 1, Org 25969 or placebo was administered to 19 subjects during one to three treatment periods each. In part 2, a further 10 subjects received general anesthesia on two separate occasions, using an intubating dose of 0.6 mg/kg rocuronium. Three minutes after rocuronium administration, Org 25969 or placebo was given in random order. Six doses of 0.1-8.0 mg/kg Org 25969 were evaluated. Neuromuscular block was measured using an acceleromyograph, the TOF-Watch-SX (NV Organon, Oss, The Netherlands).

Results

All adverse events related to Org 25969 treatment were of limited duration and mild intensity, except for a period of paresthesia, seen in one patient receiving 8 mg/kg Org 25969, which was of moderate intensity. No adverse events required any treatment, and all subjects recovered from them. When 8 mg/kg Org 25969 was given, the train-of-four ratio returned to 0.9 within 2 min after its administration. No signs of recurarization were observed.

Conclusions

Org 25969 was both well tolerated and effective in reversing neuromuscular block induced by rocuronium in 29 human volunteers.
Dose-dependent Inhibition of Platelet Function by Acetaminophen in Healthy Volunteers
Authors: Munsterhjelm Edward , Munsterhjelm Nina M. , Niemi Tomi T. , Ylikorkala Olavi , Neuvonen Pertti J. , Rosenberg Per H.
Published: September 2005

Background

Acetaminophen (paracetamol) is widely used for postoperative analgesia. Its mechanism of action is inhibition of prostaglandin synthesis in the central nervous system, and acetaminophen is traditionally not considered to influence platelet function. The authors studied the dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers.

Methods

Thirteen healthy male volunteers (aged 19-26 yr) were given placebo or 15, 22.5, or 30 mg/kg acetaminophen intravenously in a double-blind, crossover study. Ten and 90 min after infusion, platelet function was assessed by photometric aggregometry and by measuring release of thromboxane B2, analgesia by cold pressor test, and plasma acetaminophen concentrations by high-performance liquid chromatography.

Results

When triggered with 500 microm arachidonic acid, median platelet aggregation (area under the curve) was 25.7, 22.8, 4.1, or 3.6 x 10 area units (P < 0.001) 10 min after placebo or 15, 22.5, or 30 mg/kg acetaminophen, respectively. An increasing concentration of arachidonic acid attenuated the antiaggregatory effect. After 90 min, platelet function was recovering. Release of thromboxane B2 was also dose-dependently inhibited by acetaminophen. Although plasma concentration of acetaminophen increased linearly with the dose, no analgesic effect was detected in the cold pressor test.

Conclusions

Acetaminophen, which is a weak inhibitor of platelet cyclooxygenase 1, has a dose-dependent antiaggregatory effect. This property may become clinically significant in patients with intrinsic or drug-induced impairment of hemostasis.
Prevention of Hypotension during Spinal Anesthesia for Cesarean Delivery
Authors: Kee Warwick D. Ngan , Khaw Kim S. , Ng Floria F.
Published: September 2005

Background

Many methods for preventing hypotension during spinal anesthesia for cesarean delivery have been investigated, but no single technique has proven to be effective and reliable. This randomized study studied the efficacy of combining simultaneous rapid crystalloid infusion (cohydration) with a high-dose phenylephrine infusion.

Methods

Nonlaboring patients scheduled to undergo elective cesarean delivery received an intravenous infusion of 100 mug/min phenylephrine that was started immediately after spinal injection and titrated to maintain systolic blood pressure near baseline values until uterine incision. In addition, patients received infusion of lactated Ringer's solution that was given either rapidly (group 1, n = 57) or at a minimal maintenance rate (group 0, n = 55). Maternal hemodynamic changes and neonatal condition were compared.

Results

Six patients were excluded from analysis. Only 1 of 53 patients (1.9% [95% confidence interval, 0.3-9.9%]) in group 1 experienced hypotension versus 15 of 53 patients (28.3% [95% confidence interval, 18.0-41.6%]) in group 0 (P = 0.0001). Compared with group 0, patients in group 1 had greater values for the following: serial measurements of systolic blood pressure (P = 0.02), minimum recorded systolic blood pressure (P = 0.0002), and minimum recorded heart rate (P = 0.013). Total phenylephrine consumption was smaller in group 1 compared with group 0 (P = 0.008). Neonatal outcome and maternal side effects were similar between groups.

Conclusions

Combination of a high-dose phenylephrine infusion and rapid crystalloid cohydration is the first technique to be described that is effective for preventing hypotension during spinal anesthesia for cesarean delivery.
Influence of Nociception and Stress-induced Antinociception on Genetic Variation in Isoflurane Anesthetic Potency among Mouse Strains
Authors: Mogil Jeffrey S. , Smith Shad B. , O'Reilly Meghan K. , Plourde Gilles
Published: September 2005

Background

Genetic background influences anesthetic potency to suppress motor response to noxious stimulation (minimum alveolar concentration [MAC]) as well as nociceptive sensitivity in unmedicated animals. However, the influence on MAC of baseline sensitivity to the noxious stimuli used to assess MAC has virtually never been studied. The authors assessed room air nociceptive sensitivity and isoflurane MAC in multiple mouse strains. Isoflurane requirement for loss of righting response (MACLORR) was also measured.

Methods

One outbred and 10 inbred mouse strains were tested for latency to respond (in room air) to a tail clip (either 500 g or 2,000 g). Naive mice of the same 11 strains were tested for isoflurane MAC and MACLORR. To assess the role of opioid-mediated stress-induced antinociception, mice were also tested for nociceptive sensitivity after injection of naloxone (10 mg/kg) or saline.

Results

Robust strain differences were observed for all measures. The authors found that tail-clip latency (using a 500-g or 2,000-g clip, respectively) correlated significantly with MAC (r = -0.76 and -0.58, respectively) but not MACLORR (r = -0.10 and -0.26). Naloxone produced strain-dependent reductions in open air tail-clip latencies, and these reductions were also strongly correlated with MAC (r = -0.67 and -0.71).

Conclusions

The authors suggest that genetic variability in isoflurane MAC (but not MACLORR) may reflect genetic variability in the underlying sensitivity to the noxious stimulus being used to measure MAC. This variable sensitivity to nociception in the awake state is at least partially mediated by endogenous antinociceptive mechanisms activated by the tail-clip stimulus itself.
Cholinesterases and the Resistance of the Mouse Diaphragm to the Effect of Tubocurarine
Authors: Nguyen-Huu Tu , Dobbertin Alexandre , Barbier Julien , Minic Jasmina , Krejci Eric , Duvaldestin Philippe , Molgó Jordi
Published: September 2005

Background

The diaphragm is resistant to competitive neuromuscular blocking agents. Because of the competitive mechanism of action of tubocurarine, the rate of hydrolysis of acetylcholine at the neuromuscular junction may modulate its neuromuscular blocking effect. The authors compared the neuromuscular blocking effect of tubocurarine on isolated diaphragm and extensor digitorum longus (EDL) muscles and quantified the acetylcholinesterase activity in hetero-oligomers.

Methods

Adult Swiss-Webster and collagen Q-deficient (ColQ) mice were used. The blocking effect of tubocurarine on nerve-evoked muscle twitches was determined in isolated diaphragm and EDL muscles, after inhibition of acetylcholinesterase by fasciculin-1, butyrylcholinesterase by tetraisopropylpyro-phosphoramide, or both acetylcholinesterase and butyrylcholinesterase by neostigmine, and in acetylcholinesterase-deficient ColQ muscles. The different acetylcholinesterase oligomers extracted from diaphragm and EDL muscles were quantified in sucrose gradient.

Results

The EC50 for tubocurarine to decrease the nerve-evoked twitch response was four times higher in the diaphragm than in the EDL. The activity of the different acetylcholinesterase oligomers was lower in the diaphragm as compared with the EDL. Inhibition of acetylcholinesterase by antagonists resulted in an increased dose of tubocurarine but an unchanged resistance ratio between the diaphragm and the EDL. A similar diaphragmatic resistance was found in ColQ muscles.

Conclusion

The current study indicates that, despite differences in acetylcholinesterase activity between the diaphragm and EDL, the diaphragmatic resistance to tubocurarine cannot be explained by the different rate of acetylcholine hydrolysis in the synaptic cleft.