bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of third-harmonic generation in a polymer-dispersed liquid-crystal grating
Authors: Markowicz Przemyslaw P. , Hsiao Vincent K. S. , Tiryaki Hanifi , Cartwright Alexander N. , Prasad Paras N. , Dolgaleva Ksenia , Lepeshkin Nick N. , Boyd Robert W.
Published: July 2005

We report the observation of significant enhancement of one-step third-harmonic generation in a one-dimensional photonic crystal pumped by a near-infrared laser beam tuned to the low-frequency edge of the first photonic band gap. The third-harmonic phase matching can be controlled by changing the angle of incidence of the fundamental radiation, allowing tunability of the third-harmonic wavelength. The observed phenomenon was modeled theoretically using the transfer-matrix method. The enhancement is attributed to the combined action of phase-matching between the pump and harmonic waves and pump-field localization within the photonic crystal.
Simulation of environment effects on retroreflectors in ITER
Authors: Voitsenya V. S. , Donné A. J. H. , Bardamid A. F. , Belyaeva A. I. , Berezhnyj V. L. , Galuza A. A. , Gil Ch. , Konovalov V. G. , Lipa M. , Malaquais A. , Naidenkova D. I. , Ryzhkov V. I. , Schunke B. , Solodovchenko S. I. , Topkov A. N.
Published: July 2005

Two plasma diagnostics in ITER will use cube-corner reflectors (CCR): poloidal polarimetry and toroidal interferometry/polarimetry. The multichannel poloidal polarimetry system is planned to operate at a wavelength of 118.8μm. The multichannel toroidal interferometry/polarimetry system is based on a CO2 laser operating at wavelengths of 10.6 and 9.27μm. The long term sputtering by charge exchange atoms and/or deposition of carbon-based (or beryllium-based) contaminant layers can affect the optical properties of the CCR. The role of both these potentially deleterious effects on the CCR operation is analyzed in this article, taking into account the probing beam wavelength and the CCR locations. The conclusion is that for the intended use of a CCR in the poloidal polarimetry at 118μm neither erosion nor deposition should pose a problem. On the other hand, in the toroidal interferometry/polarimetry system operating at 10μm, care must be taken to reduce the charge exchange atom flux and it is likely that deposition will occur and could have deleterious effects especially on the polarization properties of the reflected radiation.
Modeling subgrid-scale effects on particles by approximate deconvolution
Authors: Shotorban Babak , Mashayek Farzad
Published: July 2005

The approximate deconvolution is implemented to reconstruct the instantaneous velocities from the filtered velocities before using them in the momentum equations of particles in the large-eddy simulation (LES) of particle-laden turbulent flows. It is shown that the various statistics of particles obtained through deconvolution are in good agreement with those obtained by the direct numerical simulation (DNS) by conducting a priori and a posteriori tests in a particle-laden homogeneous shear turbulent flow. On the other hand, the neglect of the effects of subgrid scales on the particles results in discrepancies between DNS and LES results.
Three-dimensional atom mapping of dopants in Si nanostructures
Authors: Thompson Keith , Booske John H. , Larson David J. , Kelly Thomas F.
Published: July 2005

Atom-probe tomography has successfully mapped three-dimensional (3D) dopant atom distributions in nanoscale volumes of Si subjected to various processing procedures. The 3D evolution of dopants, specifically effects such as dopant clustering and grain-boundary segregation, were analyzed in implanted polycrystalline Si gate contacts and implanted shallow junctions. A cluster of dimensions 2×7×8nm3 and containing 264 B atoms, was identified at the intersection of three poly-Si grains, verifying that annealing highly overdoped thin poly-Si layers does not facilitate uniformly doped and highly conductive gate contact layers.
Nanostaircases: An atomic shadowing instability during epitaxial CrN(001) layer growth
Authors: Frederick J. R. , Gall D.
Published: July 2005

Epitaxial CrN(001) layers, 57 and 230 nm thick, were grown on MgO(001) at 700 °C by ultrahigh-vacuum magnetron sputter deposition in pure N2 discharges. An oblique deposition angle α=80° was utilized to purposely increase the effect of atomic shadowing on surface morphological and microstructural evolution. The layers are single crystals with a surface morphology that is characterized by dendritic ridge patterns extending along orthogonal ⟨110⟩ directions superposed by square-shaped supermounds with ⟨100⟩ edges. The ridge patterns are due to a two-dimensional growth instability related to a gradient in the adatom density while the supermounds form due to atomic shadowing. The supermounds protrude out of the surface and capture a larger deposition flux than the surrounding layer. This leads to both vertical and lateral growth and the formation of inverted pyramids that are epitaxially embedded in a single crystalline matrix. The inverted pyramids are terminated by 1–3-nm-wide tilted voids that form nanostaircases due to kinetic faceting along orthogonal {100} planes.
Room-temperature plasma waves resonant detection of sub-terahertz radiation by nanometer field-effect transistor
Authors: Teppe F. , Knap W. , Veksler D. , Shur M. S. , Dmitriev A. P. , Kachorovskii V. Yu. , Rumyantsev S.
Published: July 2005

We report on room-temperature, resonant detection of 0.6THz radiation by 250nm gate length GaAs∕AlGaAs heterostructure field-effect transistor. We show that the detection is strongly increased (and becomes resonant) when the drain current increases and the transistor is driven into the current saturation region. We interpret the results as due to resonant plasma wave detection that is enhanced by increasing the electron drift velocity.
Early-stage suppression of Cu (001) oxidation
Authors: Eastman J. A. , Fuoss P. H. , Rehn L. E. , Baldo P. M. , Zhou G.-W. , Fong D. D. , Thompson L. J.
Published: July 2005

In situ synchrotron x-ray studies of the early-stage oxidation behavior of Cu (001) reveal that for Cu2O nanoislands, the Cu–Cu2O equilibrium phase boundary is shifted to larger oxygen partial pressure (pO2) by many orders of magnitude relative to bulk Cu2O. Real-time scattering measurements find that an ordered surface structure appears with increasing pO2, followed by the nucleation of epitaxial Cu2O nanoislands. By adjusting the pO2, it is possible to reversibly grow or shrink these islands and accurately determine the equilibrium phase boundary. These observations provide insight into the general stability of oxide nanoclusters grown by various techniques.
Influence of self-trapped states on the fluorescence intermittency of single molecules
Authors: Schuster Jörg , Cichos Frank , von Borczyskowski Christian
Published: July 2005

We present data on photoinduced fluorescence intermittency of single terrylene molecules embedded in polymer films. Intermittency statistics follow power laws on time scales from tens of milliseconds to tens of seconds. Power law exponents vary with the polarity of the medium while the probability of long dark periods is drastically increased in the more polar matrix. Our experiments support a picture, which assumes a molecule charged by photoexcitation and coupled to a broad manifold of (charged) self-trapped states stabilized by the dielectric response of the surrounding matrix. This model is able to explain long living dark states both for semiconductor nanoparticles and fluorescent dye molecules making use of a unique microscopic description. It also takes into account a competitive photoinduced irreversible bleaching of the molecular state.
Suppression of the photoluminescence quenching effect in self-assembled InAs∕GaAs quantum dots
Authors: Baidus N. V. , Chahboun A. , Gomes M. J. M. , Vasilevskiy M. I. , Demina P. B. , Uskova E. A. , Zvonkov B. N.
Published: July 2005

We report results that witness the possibility of controlling the temperature (T) dependence of the photoluminescence (PL) from self-assembled InAs∕GaAs quantum dots (QDs) overgrown by an InxGa1−xAs layer forming a quantum well. A growth treatment using tetrachloromethane eliminates the quenching of the PL intensity at room temperature. A reduction in the concentration of defects in the GaAs matrix and the corresponding increase of the radiative lifetime of the photocarriers are invoked to explain this effect. A simple model analyzing the behavior of the quasi-Fermi level in the QD heterostructure confirms our explanation.
Physical mechanism of oxide interfacial traps, carrier mobility degradation and series resistance on contrast reversal in scanning-capacitance-microscopy dopant concentration extraction
Authors: Wong K. M. , Chim W. K. , Yan J.
Published: July 2005

In this letter, the contrast reversal effect in scanning-capacitance-microscopy (SCM) dopant concentration extraction is investigated both theoretically and experimentally. The shift of the turning point in the nonmonotonic response of peak dC∕dV signal versus dopant concentration to higher dopant concentrations is explained by the difference of the capture/emission time constant of the interface states and the series resistance of the semiconductor sample. This is verified by comparing the experimental SCM measurements with the simulated peak dC∕dV profile on a p-type multiple dopant step sample. The contrast reversal effect, which affects the accuracy of dopant concentration extraction using the SCM peak dC∕dV signal, can be minimized by using an overlying oxide with good interfacial quality and a semiconductor sample of low series resistance.
Photon correlation studies of single GaN quantum dots
Authors: Santori Charles , Götzinger Stephan , Yamamoto Yoshihisa , Kako Satoshi , Hoshino Katsuyuki , Arakawa Yasuhiko
Published: July 2005

We present measurements of the second-order coherence function on emission from single GaN quantum dots. In some cases a large degree of photon antibunching is observed, demonstrating isolation of a single quantum system. For a selected quantum dot, we study the dependence of photon antibunching on excitation power and temperature. Using pulsed excitation, we demonstrate an ultraviolet triggered single-photon source operating at a wavelength of 358nm.
Field desorption ion source for neutron generators
Authors: Schwoebel P. R.
Published: July 2005

An investigation of an electrostatic field desorption source of atomic deuterium ions for neutron generators is presented. The source is shown to produce deuteron ions in pulse durations as short as 20ns. This ion source has the potential to facilitate the development of long-life portable neutron generators with neutron outputs scalable from ∼107n∕s to greater than 1010n∕s for active neutron interrogation systems.
Short wavelength intersubband emission from InAs∕AlSb quantum cascade structures
Authors: Barate D. , Teissier R. , Wang Y. , Baranov A. N.
Published: July 2005

The InAs∕AlSb material system is a promising candidate for the development of short wavelength quantum cascade lasers because of the large conduction band offset of 2.1 eV. In this letter, we present a study of room temperature electroluminescence of InAs∕AlSb quantum cascade structures as a function of the emission wavelength. Intersubband emission with a transition energy of 500 meV (λ=2.5μm) has been obtained.
Measuring the continuity of diffusion barriers on porous films using γ-ray energy spectra of escaping positronium
Authors: Xu Jun , Mills Allen P. , Case Carlye
Published: July 2005

Diffusion barriers for capping porous low dielectric constant films are important for preventing metal migration into a semiconductor circuit. Using the fact that positrons implanted into a porous dielectric form ortho-positronium (o-Ps) copiously, Gidley et al. [D. W. Gidley, W. F. Frieze, T. L. Dull, J. Sun, A. F. Yee, C. V. Nguyen, and D. Y. Yoon, Appl. Phys. Lett. 76, 1282 (2000)], have been able to measure open area fractions as low as 10−5 in porous dielectric film barrier layers from the increase in the ortho-positronium lifetime and intensity associated with positronium escape into vacuum. We demonstrate that it is possible to obtain comparable sensitivities by measuring the gamma-ray energy spectrum of the escaping positronium.
W
2
B
-based rectifying contacts to n-GaN
Authors: Khanna Rohit , Pearton S. J. , Ren F. , Kravchenko I. , Kao C. J. , Chi G. C.
Published: July 2005

Schottky contact formation on n-GaN using a novel W2B∕Ti∕Au metallization scheme was studied using current-voltage, scanning electron microscopy and Auger electron spectroscopy measurements. A maximum barrier height of 0.55 eV was achieved on as-deposited samples, with a negative temperature coefficient of 8×10−4eV∕°C over the range 25–150 °C. There was also a negative temperature coefficient for the reverse breakdown of the Schottky diodes with W2B contacts. The barrier height was essentially independent of annealing temperature up to 500 °C and decreased thereafter due to the onset of metallurgical reactions with the GaN. The Ti began to out-diffuse to the surface at temperatures of >500°C. The reverse current magnitude was larger than predicted by thermionic emission alone.
He
3
polarization via optical pumping in a birefringent cell
Authors: Masuda Y. , Ino T. , Skoy V. R. , Jones G. L.
Published: July 2005

A sapphire cell was used to obtain a high He3 nuclear polarization by means of spin-exchange optical pumping. The phase-shift difference between ordinary and extraordinary rays is well controlled using the thickness of the birefringent sapphire window so that a high circular polarization is obtained in the cell. Neutron transmission through the polarized He3 gas was measured as a function of neutron energy. A large He3 polarization of 63±1% was obtained at a He3 pressure of 3.1 atm. Neutron polarizations of 97 and 90 % were obtained with transmission rates of 15 and 22 % at 10 and 20 meV, respectively.
Identification of longitudinal optical modes by hyper-Raman scattering in noncentrosymmetric ceramics
Authors: Hellwig Holger
Published: July 2005

Hyper-Raman scattering has been applied to ceramic samples of noncentrosymmetric lead zirconate titanate (PZT5H). The intense second-harmonic signal was blocked by using a holographic notch filter. Based on comparison with conventional Raman spectra taken under the same conditions, LO mode frequencies could be derived directly from the hyper-Raman spectra. The assignment of LO mode frequencies based on hyper-Raman spectra provides the possibility to measure LO-TO splitting in noncentrosymmetric ceramics, for which conventional Raman measurements alone provide only limited information.
Visual Representations of Dynamic Actions from Static Pictures
Authors: Bonnet Claude , Paulos Carlos , Nithart Christelle
Published: July 2005

We investigated how subjects used their knowledge of biomechanical constraints when judging whether different items were in balance or in the process of falling, as a function of their angle of slant. In the first experiment, the stimuli were pictures of postures of a human body, of a wooden mannequin, and of a skeleton. The results show that for these 3 items, fall responses appeared for a smaller slant angle for a backward slant than for a forward one. This difference may reflect the influence of biomechanical constraints. To verify whether the asymmetry of the responses to the mannequin and the skeleton was genuine or due to some semantic context effect, a second experiment was run with only pictures of a wooden mannequin. The same asymmetry was observed. In a third experiment, falling judgments were obtained for pictures of a human body and of a structurally comparable artifactual object. The asymmetry of the fall responses appeared only for the human body.
The Roles of Inducer Size and Distance in the Ebbinghaus Illusion (Titchener Circles)
Authors: Roberts Brian , Harris Mike G , Yates Tim A
Published: July 2005

Although the Ebbinghaus illusion is commonly used as an example of a simple size-contrast effect, previous studies have emphasised its complexity by identifying many factors that potentially influence the magnitude of the illusion. Here, in a series of three experiments, we attempt to simplify this complexity. In each trial, subjects saw a display comprising, on one side, a target stimulus surrounded by inducers and, on the other, an isolated probe stimulus. Their task was to indicate whether the probe appeared larger or smaller than the target. Probe size was adjusted with a one-up, one-down staircase procedure to find the point of subjective equality between probe and target. From these experiments, we argue that the apparent effects of inducer size are often confounded by the relative completeness of the inducing surround and that factors such as the similarity of the inducers and target are secondary. We suggest a simple model that can explain most of the data in terms of just two primary and independent factors: the relative size of the inducers and target, and the distance between the inducers and the target. The balance between these two factors determines whether the size of the target is underestimated or overestimated.
Ames's Window in Proprioception
Authors: Bruno Nicola , Dell'Anna Alessandro , Jacomuzzi Alessandra
Published: July 2005

When holding a small-scale model of Ames's trapezoidal window with the arms fully extended, several observers experience a striking proprioceptive distortion (eg one hand appears farther from the other, or one arm appears longer than the other). However, data from a matching experiment suggest that the proprioceptive misalignment of the hands is, in fact, rather less than the apparent slant of the window when this is not held. This finding argues against a ‘visual-capture’ account, supports an explanation in terms of bimodal integrative processes, and underscores the importance of supplementing phenomenological observations with objective measures.
The role of osmotolerant rhizobacteria in rice growth under different drought conditions
Authors: Yuwono Triwibowo , Handayani Desi , Soedarsono Joedoro
Published: July 2005

Osmotolerant rhizobacterial isolates were used as inoculants for rice under different drought conditions in a greenhouse. Rice was grown on a Regosol, under either sterile or non-sterile conditions, in which the water level was adjusted to 80% and 40% of field capacity. Rice seed was inoculated with osmotolerant rhizobacterial isolates (isolates Al-19, A82, and M7b) and grown until the plant reached maximum vegetative phase (86 days from seed sowing). Inocula used were: Al-19 plus A82, Al-19 plus M7b, A82 plus M7b, and a mixture of 3 isolates. Under sterile conditions, inoculation of rice with the different inocula resulted in an increase in shoot dry weight, root dry weight, and number of tillers of 0–45.72%, 0.62–79.67%, and 0– 61.11%, respectively. Under non-sterile condition, shoot dry weight, root dry weight, and number of tillers increased by 19.66–28.04%, 14.00–91.33%, and 14.29–157.14%, respectively. The study also demonstrated that the role of osmotolerant rhizobacteria was more pronounced at 40% field capacity than 80% field capacity.
Hardseededness in Mediterranean annual pasture legumes in Australia: a review
Authors: Taylor G. B.
Published: July 2005

Hardseededness (seed coat impermeability) is the main seed dormancy mechanism for regulating germination of annual pasture legumes both within and between years. Progress made in Australia over the past 30 years towards an understanding and better utilisation of the mechanism is the subject of this review, together with relevant overseas studies. Although some legumes produce virtually no hard seeds, newly ripened seeds of most cultivated annual pasture legumes are >90% hard when produced under favourable seed maturation conditions. The pattern of seed softening (loss of impermeability) varies widely among legumes both within and between years and is one of the more important considerations in selection programs. The many factors that influence the longevity of seed hardness are described. Differences among legumes in patterns of summer and autumn seed softening, which may influence the extent of seed losses through false breaks of season, are explained in terms of a 2-stage conceptual model of the seed softening process. This model has led to the development of laboratory techniques that effectively simulate field softening behaviour in a wide range of legumes. Different rates of seed imbibition, which may be attributable to a previously unrecognised stage in the seed softening process, and which can offer some further protection against false breaks of season are also described. The wide range of seed softening characteristics that are now recognised provides opportunities for better adapting pasture legumes to particular management systems, including rotations with crops.
The timing of flush development affects the flowering of avocado (Persea americana) and macadamia (Macadamia integrifolia × tetraphylla)
Authors: Olesen Trevor
Published: July 2005

Orchard trees of A4 macadamia (Macadamia integrifolia × tetraphylla) and Hass avocado (Persea americana) were thinned and tip-pruned at different times to generate a range of trees with different stages of leafy flush development. The stagger in the start of the first flush following pruning was repeated in the start of subsequent flushes, so pruning was an effective means of changing the phase of the cycle of flush development. The difference in phase affected flowering. In macadamia, over 80% of the variance in flowering was explained by regression against pruning time. Flowering ranged from 0 to 43% of tip-pruned branches, with the most profuse flowering on flushes appearing in July. In avocado, over 45% of the variance in flowering of the first flush following pruning, and over 35% of the second flush, was explained by regression against pruning time, with more flowering on those flushes starting nearer to the winter solstice. The control trees flowered better than the pruned trees but there was too little information to explain the difference. The macadamia control trees had less synchronised flushing than the pruned trees, and were not subject to internal thinning. The avocado control trees appeared to have a phase of flush development different from the pruned trees, with a summer flush commencing before the first pruning date and maturing before the maturation of the first post-pruning flushes. More research is needed for related canopy management guidelines.
AFLP and SSR analysis of genetic diversity among landraces of bread wheat (Triticum aestivum L. em. Thell) from different geographic regions
Authors: Stodart B. J. , Mackay M. , Raman H.
Published: July 2005

A set of 44 bread wheat landraces was used to determine the efficacy of 16 amplifed fragment length polymorphism (AFLP) primers and 63 wheat simple sequence repeat (SSR) markers in identifying polymorphisms between accessions. The SSR markers detected approximately 10 alleles per locus with a mean gene diversity (Hz) of 0.63, whereas AFLP primers identified approximately 147 fragments per primer with a mean gene diversity of 0.25. A set of 54 SSR markers and 11 AFLP primers was identified as highly polymorphic (polymorphic information content (PIC) ≥ 0.5 and 0.3 for SSR and AFLP, respectively), and suitable for molecular characterisation of germplasm. Principle coordinate analysis suggested that the AFLP and SSR loci could be used to discriminate among accessions collected from North Africa and southern Europe from those collected from the Middle East. Both marker types indicate that accessions from North Africa and southern Europe, the Middle East, and southern and eastern Asia are genetically diverse. The results indicate the usefulness of the molecular markers to assess genetic diversity present within germplasm collections.
Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City
Authors: Olson Donald R. , Simonsen Lone , Edelson Paul J. , Morse Stephen S.
Published: July 2005

The 1918 “Spanish flu” was the fastest spreading and most deadly influenza pandemic in recorded history. Hypotheses of its origin have been based on a limited collection of case and outbreak reports from before its recognized European emergence in the summer of 1918. These anecdotal accounts, however, remain insufficient for determining the early diffusion and impact of the pandemic virus. Using routinely collected monthly age-stratified mortality data, we show that an unmistakable shift in the age distribution of epidemic deaths occurred during the 1917/1918 influenza season in New York City. The timing, magnitude, and age distribution of this mortality shift provide strong evidence that an early wave of the pandemic virus was present in New York City during February-April 1918.
Jade-1, a candidate renal tumor suppressor that promotes apoptosis
Authors: Zhou Mina I. , Foy Rebecca L. , Chitalia Vipul C. , Zhao Jin , Panchenko Maria V. , Wang Hongmei , Cohen Herbert T.
Published: July 2005

Medical therapies are lacking for advanced renal cancer, so there is a great need to understand its pathogenesis. Most renal cancers have defects in the von Hippel-Lindau tumor suppressor pVHL. The mechanism by which pVHL protein functions in renal tumor suppression remains unclear. Jade-1 is a short-lived, kidney-enriched transcription factor that is stabilized by direct interaction with pVHL. Loss of Jade-1 stabilization by pVHL correlates with renal cancer risk, making the relationship between Jade-1 and renal cancer compelling. We report that Jade-1 expression was barely detectable in all tested renal cancer cell lines, regardless of
VHL
status. Strikingly, proteasome inhibitor treatment increased endogenous Jade-1 expression up to 10-fold. Jade-1 inhibited renal cancer cell growth, colony formation, and tumor formation in nude mice. Intriguingly, Jade-1 also affected the pattern of cell growth in monolayer culture and 3D culture. Jade-1 increased apoptosis by 40-50% and decreased levels of antiapoptotic Bcl-2. Antisense Jade-1-expressing cells confirmed these results. Therefore, Jade-1 may suppress renal cancer cell growth in part by increasing apoptosis. Jade-1 may represent a proapoptotic barrier to proliferation that must be overcome generally in renal cancer, perhaps initially by pVHL inactivation and subsequently by increased proteasomal activity. Therefore, Jade-1 may be a renal tumor suppressor.
Crystalline molecular machines: Encoding supramolecular dynamics into molecular structure
Authors: Garcia-Garibay Miguel A.
Published: July 2005

Crystalline molecular machines represent an exciting new branch of crystal engineering and materials science with important implications to nanotechnology. Crystalline molecular machines are crystals built with molecules that are structurally programmed to respond collectively to mechanic, electric, magnetic, or photonic stimuli to fulfill specific functions. One of the main challenges in their construction derives from the picometric precision required for their mechanic operation within the close-packed, self-assembled environment of crystalline solids. In this article, we outline some of the general guidelines for their design and apply them for the construction of molecular crystals with units intended to emulate macroscopic gyroscopes and compasses. Recent advances in the preparation, crystallization, and dynamic characterization of these interesting systems offer a foothold to the possibilities and help highlight some avenues for future experimentation.
Engineering a signal transduction mechanism for protein-based biosensors
Authors: Kohn Jonathan E. , Plaxco Kevin W.
Published: July 2005

Hybridization-induced conformational changes have been successfully used in biosensors for the transduction of DNA-binding events into readily observable optical or electronic signals. Similar signal transduction has not, however, proven of equal utility in proteinbased biosensors. The discrepancy arises because, unlike ssDNA, most proteins do not undergo significant conformational changes upon ligand binding. Here, we describe a solution to this problem. We show that an arbitrarily selected, normally well folded protein can be rationally engineered such that it undergoes ligand-induced folding. The engineered protein responds rapidly (milliseconds) and selectively to its target, and it couples recognition with the largest possible conformational change: folding. These traits suggest that ligand-induced folding could serve as an ideal signal-transduction mechanism. Consistent with this claim, we demonstrate a label-free optical biosensor based on the effect that is sufficiently selective to detect its target even in complex, contaminant-ridden samples such as blood serum.
NK cytotoxicity against CD4+T cells during HIV-1 infection: A gp41 peptide induces the expression of an NKp44 ligand
Authors: Vieillard Vincent , Strominger Jack L. , Debré Patrice
Published: July 2005

HIV infection leads to a state of chronic immune activation and progressive deterioration in immune function, manifested most recognizably by the progressive depletion of CD4+T cells. A substantial percentage of natural killer (NK) cells from patients with HIV infection are activated and express the natural cytotoxicity receptor (NCR) NKp44. Here we show that a cellular ligand for NKp44 (NKp44L) is expressed during HIV-1 infection and is correlated with both the progression of CD4+T cell depletion and the increase of viral load. CD4+T cells expressing this ligand are highly sensitive to the NK lysis activity mediated by NKp44+NK cells. The expression of NKp44L is induced by the linear motif NH2-SWSNKS-COOH of the HIV-1 envelope gp41 protein. This highly conserved motif appears critical to the sharp increase in NK lysis of CD4+T cells from HIV-infected patients. These studies strongly suggest that induction of NKp44L plays a key role in the lysis of CD4+T cells by activated NK cells in HIV infection and consequently provide a framework for considering how HIV-1 may use NK cell immune surveillance to trigger CD4+T cells. Understanding this mechanism may help to develop future therapeutic strategies and vaccines against HIV-1 infection.
Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases
Authors: Carter Todd A. , Wodicka Lisa M. , Shah Neil P. , Velasco Anne Marie , Fabian Miles A. , Treiber Daniel K. , Milanov Zdravko V. , Atteridge Corey E. , Biggs William H. , Edeen Philip T. , Floyd Mark , Ford Julia M. , Grotzfeld Robert M. , Herrgard Sanna , Insko Darren E. , Mehta Shamal A. , Patel Hitesh K. , Pao William , Sawyers Charles L. , Varmus Harold , Zarrinkar Patrick P. , Lockhart David J.
Published: July 2005

To realize the full potential of targeted protein kinase inhibitors for the treatment of cancer, it is important to address the emergence of drug resistance in treated patients. Mutant forms of BCR-ABL, KIT, and the EGF receptor (EGFR) have been found that confer resistance to the drugs imatinib, gefitinib, and erlotinib. The mutations weaken or prevent drug binding, and interestingly, one of the most common sites of mutation in all three kinases is a highly conserved “gatekeeper” threonine residue near the kinase active site. We have identified existing clinical compounds that bind and inhibit drug-resistant mutant variants of ABL, KIT, and EGFR. We found that the Aurora kinase inhibitor VX-680 and the p38 inhibitor BIRB-796 inhibit the imatinib- and BMS-354825-resistant ABL(T315I) kinase. The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase. EKB-569 and CI-1033 are already in clinical trials, and our results suggest that they should be considered for testing in the treatment of gefitinib/erlotinib-resistant non-small cell lung cancer. The results highlight the strategy of screening existing clinical compounds against newly identified drug-resistant mutant variants to find compounds that may serve as starting points for the development of next-generation drugs, or that could be used directly to treat patients that have acquired resistance to first-generation targeted therapy.
Pluralism without Genic Causes?*
Authors: Lloyd Elisabeth A. , Dunn Matthew , Cianciollo Jennifer , Mannouris Costas
Published: July 2005

Since the fundamental challenge that I laid at the doorstep of the pluralists was to defend, with nonderivative models, a strong notion of genic cause, it is fatal that Waters has failed to meet that challenge. Waters agrees with me that there is only a single cause operating in these models, but he argues for a notion of causal ‘parsing’ to sustain the viability of some form of pluralism. Waters and his colleagues have some very interesting and important ideas about the sciences, involving pluralism and parsing or partitioning causes, but they are ideas in search of an example. He thinks he has found an example in the case of hierarchical and genic selection. I think he has not.
TileMap: create chromosomal map of tiling array hybridizations
Authors: Ji Hongkai , Wong Wing Hung
Published: July 2005

Motivation: Tiling array is a new type of microarray that can be used to survey genomic transcriptional activities and transcription factor binding sites at high resolution. The goal of this paper is to develop effective statistical tools to identify genomic loci that show transcriptional or protein binding patterns of interest.

Results: A two-step approach is proposed and is implemented in TileMap. In the first step, a test-statistic is computed for each probe based on a hierarchical empirical Bayes model. In the second step, the test-statistics of probes within a genomic region are used to infer whether the region is of interest or not. Hierarchical empirical Bayes model shrinks variance estimates and increases sensitivity of the analysis. It allows complex multiple sample comparisons that are essential for the study of temporal and spatial patterns of hybridization across different experimental conditions. Neighboring probes are combined through a moving average method (MA) or a hidden Markov model (HMM). Unbalanced mixture subtraction is proposed to provide approximate estimates of false discovery rate for MA and model parameters for HMM.

Availability: TileMap is freely available at http://biogibbs.stanford.edu/~jihk/TileMap/index.htm

Contact:  whwong@stanford.edu

Supplementary information:  http://biogibbs.stanford.edu/~jihk/TileMap/index.htm (includes coloured versions of all figures)
BlastXtract—a new way of exploring translated searches
Authors: Claesson Marcus J. , van Sinderen Douwe
Published: July 2005

Summary: Searches of translated, unannotated genomic DNA sequences against protein databases is a useful early-stage method for discovering protein homologues encoded by the sequence, but generates huge amounts of output data that quickly become impregnable. BlastXtract is a web-based tool for managing and visualizing results from large translated BLAST and FastA searches. It combines the speed and storage benefits of relational database management systems with an easy-to-use graphical navigation map, and greatly facilitates the early exploration of genomic sequence.

Availability: BlastXtract can be downloaded from http://bioinfo.ucc.ie/blastxtract/

Contact:  mclaesson@bioinfo.ucc.ie
Efficacy and Safety of Heparinase I versus Protamine in Patients Undergoing Coronary Artery Bypass Grafting with and without Cardiopulmonary Bypass
Authors: Stafford-Smith Mark , Lefrak Edward A. , Qazi Anjum G. , Welsby Ian J. , Barber Linda , Hoeft Andreas , Dorenbaum Alejandro , Mathias Jasmine , Rochon James J. , Newman Mark F.
Published: July 2005

Background

Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aortocoronary bypass graft surgery.

Methods

In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aortocoronary bypass graft surgery patients received either heparinase I (maximum 35 microg/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was predefined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (> or = 30 mmHg decrease) and/or pulmonary hypertension (> or = 40 mmHg with an increase > or = 10 mmHg) within 30 min of heparin reversal initiation.

Results

Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery.

Conclusions

Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.
Trends but Not Individual Values of Central Venous Oxygen Saturation Agree with Mixed Venous Oxygen Saturation during Varying Hemodynamic Conditions
Authors: Dueck Michael H. , Klimek Markus , Appenrodt Stefan , Weigand Christoph , Boerner Ulf
Published: July 2005

Background

Previous studies found contradictory results regarding the question whether mixed venous oxygen saturation (Svo2) and central venous oxygen saturation (Scvo2) are equivalent. The inconsistency of study results may result from different study designs and different, partly questionable, statistical approaches.

Methods

The authors performed a prospective clinical trial comparing individual oxygen saturation values as well as the trend of values in blood from the superior vena cava (Scvo2), the right atrium (Srao2), and the pulmonary artery (Svo2) during varying hemodynamic situations. The subjects were 70 patients scheduled to undergo elective neurosurgical operations in the sitting position. Oxygen saturation was measured photospectrometrically in blood samples simultaneously taken at four different time points during supine and sitting positions. Statistical analysis was performed following the recommendations of Bland and Altman.

Results

Five hundred two comparative sets of measurements were obtained. Ninety-five percent limits of agreement ranging from +/-6.83 to +/-9.30% for single values were interpreted as clinically unacceptable. In contrast, correlations between changes of Svo2 and Scvo2 as well as of Svo2 and Srao2 were interpreted as clinically acceptable (R > or = 0.755, Pearson correlation coefficient; P < or = 0.0001).

Conclusions

In this sample of patients, exact numerical values of Scvo2 and Srao2 are not equivalent to those of Svo2 in varying hemodynamic conditions. However, for clinical purposes, the trend of Scvo2 may be substituted for the trend of Svo2. In addition, previous studies investigating the agreement between Svo2 and Scvo2 were found to be lacking in their chosen statistical approaches.
Sole Use of Dexmedetomidine Has Limited Utility for Conscious Sedation during Outpatient Colonoscopy
Authors: Jalowiecki Przemyslaw , Rudner Robert , Gonciarz Maciej , Kawecki Piotr , Petelenz Michal , Dziurdzik Piotr
Published: July 2005

Background

This study evaluated the ability of dexmedetomidine to provide analgesia and sedation for outpatient colonoscopy, examining outcomes including cardiorespiratory variables, side effects, and discharge readiness.

Methods

Sixty-four patients were randomly assigned to one of three treatment regimens. In group D, patients received 1 microg/kg dexmedetomidine over 15 min followed by an infusion of 0.2 microg x kg x h. Group P received meperidine (1 mg/kg) with midazolam (0.05 mg/kg), and group F received fentanyl (0.1-0.2 mg intravenous) on demand. The assessment included measurements of heart rate, blood pressure, oxygen saturation, respiratory rate, quality of sedation/analgesia, and an evaluation of the recovery time.

Results

The study was terminated before the planned 90 patients had been recruited because of adverse events in group D. In all groups, negligible hemoglobin oxygen saturation and respiratory rate variations were observed. In group D, there was a significantly larger decrease in heart rate (to approximately 40 beats/min in 2 of 19 cases) and blood pressure (to less than 50% of the initial value in 4 of 19 patients). Supplemental fentanyl was required in 47% of patients receiving dexmedetomidine to achieve a satisfactory level of analgesia (vs. 42.8% of patients in group P and 79.2% of patients in group F). Vertigo (5 patients), nausea/vomiting (5 patients), and ventricular bigeminy (1 patient) were observed only in group D. Time to home readiness was longest in group D (85 +/- 74, 39 +/- 21, and 32 +/- 13 min in groups D, P and F, respectively; P = 0.007).

Conclusions

The use of dexmedetomidine to provide analgesia/sedation for colonoscopy is limited by distressing side effects, pronounced hemodynamic instability, prolonged recovery, and a complicated administration regimen.
Spectral Entropy Monitoring Is Associated with Reduced Propofol Use and Faster Emergence in Propofol–Nitrous Oxide–Alfentanil Anesthesia
Authors: Vakkuri Anne , Yli-Hankala Arvi , Sandin Rolf , Mustola Seppo , Høymork Siv , Nyblom Stina , Talja Pia , Sampson Timothy , van Gils Mark , Viertiö-Oja Hanna
Published: July 2005

Background

This multicenter study evaluated the effect of a new depth of anesthesia-monitoring device based on time-frequency-balanced spectral entropy of electroencephalogram monitoring (GE Healthcare Finland, Helsinki, Finland) on consumption of anesthetic drugs and recovery times after anesthesia.

Methods

The study was a prospective, randomized, single-blind study performed in six hospitals in Finland, Sweden, and Norway. After institutional review board approval and written informed consent from each patient, the patients were randomly allocated to anesthesia with entropy values either shown (entropy group) or not shown (control group). Anesthesia was maintained with propofol, nitrous oxide, and alfentanil. In the entropy group, propofol was given to keep the state entropy value between 45 and 65, and alfentanil was given to keep the state entropy-response entropy difference below 10 units and heart rate and blood pressure within +/-20% of the baseline values. The control group patients were anesthetized to keep heart rate and blood pressure within +/-20% of the baseline values. Statistical methods included Mann-Whitney U test and unpaired t tests.

Results

A total of 368 patients were studied. In the entropy group, entropy values were higher during the whole operation and especially during the last 15 min (P < 0.001). Consequently, propofol consumption was smaller in the entropy group during the whole anesthesia period (P < 0.001) and especially during the last 15 min (P < 0.001). This shortened the time delay in the early recovery parameters in the entropy group.

Conclusion

Entropy monitoring assisted titration of propofol, especially during the last part of the procedures, as indicated by higher entropy values, decreased consumption of propofol, and shorter recovery times in the entropy group.
In Vitro Electrophysiologic Effects of Morphine in Rabbit Ventricular Myocytes
Authors: Xiao Guo-Sheng , Zhou Jing-Jun , Wang Guan-Ying , Cao Chun-Mei , Li Gui-Rong , Wong Tak-Ming
Published: July 2005

Background

Morphine is widely used in patients undergoing surgical operations and is also reported to mediate cardioprotection of preconditioning. The current study determined effects of morphine at therapeutic to pharmacologic concentrations on cardiac action potential, L-type Ca2+ current (ICa.L), delayed rectifier K+ current (IK), and inward rectifier K+ current (IK1) in isolated rabbit ventricular myocytes.

Methods

Ventricular myocytes were enzymatically isolated from rabbit hearts. Action potential and membrane currents were recorded in current and voltage clamp modes.

Results

Morphine at concentrations from 0.01 to 1 microM significantly prolonged cardiac action potential, and at 0.1 and 1 microM slightly but significantly hyperpolarized the resting membrane potential. In addition, morphine at 0.1 microM significantly augmented ICa.L (at +10 mV) from 5.9 +/- 1.9 to 7.3 +/- 1.7 pA/pF (by 23%; P < 0.05 vs. control) and increased IK1 (at -60 mV) from 2.8 +/- 1.0 to 3.5 +/- 0.9 pA/pF (by 27%; P < 0.05 vs. control). Five microM naltrindole (a selective delta-opioid receptor antagonist) or 5 microM norbinaltorphimine (a selective kappa-opioid receptor antagonist) prevented the increase in ICa.L induced by morphine, but 5 microM CTOP (a selective mu-opioid receptor antagonist) did not. The three types of opioid antagonists did not affect the augmentation of IK1 by morphine. Morphine had no effect on IK.

Conclusions

These results indicate that morphine prolongs action potential duration by increasing ICa.L, an effect mediated by delta- and kappa-opioid receptors. It also hyperpolarizes cardiac resting membrane potential by increasing IK1, which is not mediated by opioid receptors.
Anesthetics Inhibit Membrane Receptor Coupling to the Gq/11Heterotrimeric G Protein in Airway Smooth Muscle
Authors: Nakayama Tetsuzo , Hayashi Masao , Warner David O. , Jones Keith A.
Published: July 2005

Background

Some anesthetics relax airway smooth muscle in part by inhibiting acetylcholine-induced increases in Ca2+ sensitivity, an effect associated with inhibition of guanosine nucleotide exchange at the alpha subunit of the Gq/11 (Galphaq/11) heterotrimeric G protein. This study tested the hypothesis that these anesthetic effects are not unique to the muscarinic receptor but are a general property of the heptahelical receptors that increase Ca2+ sensitivity in airway smooth muscle.

Methods

Anesthetic effects on agonist-induced increases in Ca2+ sensitivity were measured in porcine airway smooth muscle strips permeabilized with S. aureus alpha-toxin. Anesthetic effects on basal (without agonist stimulation) and agonist-promoted Galphaq/11 guanosine nucleotide exchange were determined in crude membranes prepared from porcine airway smooth muscle. The nonhydrolyzable, radioactive form of guanosine 5'-triphosphate was used as the reporter for nucleotide exchange at Galphaq/11.

Results

Acetylcholine, endothelin-1, and histamine caused a concentration-dependent increase in Ca2+ sensitivity. Halothane (0.67 +/- 0.07 mM) and hexanol (10 mM) significantly inhibited the increase in Ca2+ sensitivity induced by each agonist. Each agonist also caused a time- and concentration-dependent increase in Galphaq/11 nucleotide exchange. Neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, whereas halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange promoted by each agonist.

Conclusion

These data suggest that inhibition of agonist-promoted guanosine nucleotide exchange at Galphaq/11 by some anesthetics may be a general property of heptahelical receptors involved cellular processes mediated by Galphaq/11, including muscarinic, endothelin-1, and histamine receptor activation of Ca2+ sensitivity.