bluuebunny/crossref_metadata_2025 huggingface dataset:
Auger analysis of Si–H bonding and hydrogen concentration in hydrogenated amorphous silicon
Authors: Nelson A. J. , Burnham N. A. , Schwartzlander A. B. , Asher S. E. , Kazmerski L. L.
Published: July 2002

Auger electron spectroscopy line-shape analysis of the Si-L23 VV peak has been performed on hydrogenated amorphous silicon (a-Si:H). Both a-Si:H produced by hydrogen implantation of silicon single crystals (for analytical standards) and thin films (fabricated for solar cell applications) were examined in these studies. Hydrogen concentrations were confirmed by secondary ion mass spectrometry, and samples having hydrogen content over the range 1016–1022 cm−3 were evaluated. Correlations between the area under the deconvoluted L23VV transition peak and the known hydrogen content have resulted in a semiquantitative method of determining hydrogen concentration using Auger analysis. The percentage of the L23M1M23 (sp) transition relative to the L23M23M23 ( pp) transition has been determined and also correlated with the hydrogen concentrations. These results have been compared with previously published theoretical calculations.
Frequency effects in plasma etching
Authors: Flamm Daniel L.
Published: July 2002

The effects of excitation frequency on electrical discharges used for low pressure plasma processing are discussed and illustrated with examples. Frequency alters the spatial distribution of species and electrical fields across the discharge, the energies and concentrations of species as a function of time, the characteristic potentials and energy of ions impinging on surfaces, and the electron energy distribution function. Important transitions in the behavior of these quantities occur when the excitation frequency crosses the ion-sheath transit frequency (ITF), the electron energy modulation frequency (νu), the electron momentum collision frequency (ν), and the plasma frequency (ωp).
Chemistry of hydrogen and arsenic interactions at silicon grain boundaries
Authors: Kazmerski L. L.
Published: July 2002

The incorporation of hydrogen and arsenic in silicon grain boundaries is investigated. Volume-indexed SIMS and AES are utilized for the identification of impurity species (elemental or molecular), their concentrations (quantification), and their exact spatial location (mapping). The chemistry of the interaction of the hydrogen with the ion-modified Si surface and the grain boundary is investigated for both oxygen-deficient and oxygen-rich intergrain regions. Three bonding schemes are identified, including SiH2, SiH, and SiOH. Thermal desorption studies complement the surface analytical investigations. Arsenic segregation to grain boundaries is directly demonstrated using high spatial and depth resolution volume-indexed AES. The effects of this segregation of the band structures of these grain boundaries are discussed.
Some applications of microanalytical techniques in very large scale integrated circuits fabrication
Authors: Thomas Simon
Published: July 2002

The trend in technology development for the fabrication of very large scale integrated circuits (IC’s) continues in the direction of increased density of components with smaller dimensions. Devices with submicron dimension are currently either in manufacture or in development stage. The scaling down of device dimensions, both laterally and in depth, has resulted in new challenges and developments in material and process technologies. The successful implementation of these technologies in the fabrication of reliable devices is critically dependent on the proper understanding of the material properties, the processes, and their interactions. The need for analytical tools with high spatial resolution (∼nm range), depth resolution, and ultralow detectable limits (≪parts per 109) continues. The characterization efforts have been aided by the emergence and maturing of a variety of sophisticated analytical techniques aimed at physical, chemical, and electrical characterization. The physical and chemical methods include various microscopy techniques, surface, interface, and bulk compositional analysis, and trace chemical analysis tools each with its own strengths and weaknesses. Usually multiple techniques are necessary and are used in a synergistic manner for a comprehensive analysis. The application of a particular technique varies based on the emphasis on material, process development, process monitoring, yield enhancement, or device failure analysis. Typical examples of application of various microanalytical techniques to process development for IC fabrication are presented and some of the current challenges facing analysts are identified.
An x-ray photoelectron spectroscopy study of AuxIny alloys
Authors: Jayne Douglas T. , Fatemi Navid S. , Weizer Victor G.
Published: July 2002

Four gold–indium alloys have been studied by x-ray photoelectron spectroscopy. The binding energies and intensity ratios of the Au 4f7/2 and In 3d5/2 core levels were determined for the bulk alloy compositions of Au(10% In), Au3In, AuIn, and AuIn2. These values were determined for the native oxides on the materials, for the surfaces prepared by ion bombardment to remove the oxide and for surfaces scraped in situ with a ceramic tool to expose the bulk composition. These results furnish calibration values that allow determination of the composition of thin films of this alloy system. In addition the binding energies add to the data base for understanding the effect of alloying on core level binding energies. As an illustration, these results are used to determine the composition of a series of alloy films formed by incongruent evaporation of an alloy charge.
Low voltage and high speed operating electrostatic wafer chuck
Authors: Nakasuji Mamoru , Shimizu Hiroyasu
Published: July 2002

A new electrostatic force expression for the electrostatic wafer chuck with a three layer insulator is introduced. If a few micrometers of air layer is assumed, the expression coincides with the experimental results. An electrostatic wafer chuck with a two layer insulator is designed and evaluated. The bottom layer is a spin coated polyimide and the top layer is a vacuum evaporated alumina. The holding pressure is 35 gf/cm2, when 200 V dc is applied in atmosphere. The pressure is not influenced by the duration of the applied voltage. The residual pressure, after the voltage is turned off, decreases to zero rapidly. The breakdown voltage is from 320 to 700 V. The scratch test shows good results due to a vacuum evaporated alumina layer.
Low temperature etch chuck: Modeling and experimental results of heat transfer and wafer temperature
Authors: Wright D. R. , Hartman D. C. , Sridharan U. C. , Kent M. , Jasinski T. , Kang S.
Published: July 2002

Backside-gas wafer cooling has been studied in order to better understand the control of wafer temperature in a low temperature etch tool. Thermal models were developed to predict heat transfer coefficients for helium and nitrogen backside gases. Model results were confirmed experimentally by measuring wafer cooldown times using helium and nitrogen backside gas on a commercial 150 mm wafer chuck. Additional modeling predicted the influence of gap variations on the spatial nonuniformity of wafer temperature. Further calculations detailed the effect of the choice of thermal insulating material on the total heat load to the low-temperature chuck. Additional experiments were performed with etching plasmas, using direct in situ measurement of both wafer and chuck temperatures. These results not only confirm the heat transfer calculations, they also offer an estimate of what portion of the total etch (radio frequency generator) power appears as heat in the wafer for oxide and polysilicon etch plasmas.
Hydrogen desorption behavior of aluminium materials used for extremely high vacuum chamber
Authors: Hirohata Yuko , Fujimoto Satoshi , Hino Tomoaki , Yamashina Toshiro
Published: July 2002

Hydrogen desorption properties of pure Al metal (1050H24 and 1001 Al) and Al alloy (6063T6) were investigated by using a technique of thermal desorption spectroscopy (TDS). In the TDS spectrum of hydrogen, two peaks in the temperature, which may correspond to the desorptions due to second-order surface reaction and diffusion process, were observed. The activation energy of the desorption, due to the surface reaction for the 1050H24 Al, was obtained as 38 kJ/mol. For the 1001 Al, by using a simple diffusion model, the activation energy and diffusion constant of hydrogen due to the diffusion process were calculated as 50 kJ/mol and (0.5–3.5)×10−3 cm2/s, respectively. The hydrogen desorption amount of the Al alloy was estimated as 3×1015 mol/cm2 (0.159 cc/100g Al), which was twice compared with that of the 1050H24 Al. Secondary-ion mass spectroscopy (SIMS) analysis was applied to examine the change of the surface atomic composition after baking. It was found that magnesium was considerably segregated by heating. However, the correlation between the concentrations of hydrogen and magnesium was not clearly observed.
Reactive ion etching lag investigation of oxide etching in fluorocarbon electron cyclotron resonance plasmas
Authors: Joubert O. , Oehrlein G. S. , Surendra M. , Zhang Y.
Published: July 2002

Recent selective oxide etching results obtained with an electron cyclotron resonance high-density plasma reactor are presented. Reactive ion etching lag results of patterned SiO2 samples etched with various fluorocarbon gases are discussed. A reactive ion etching lag mechanism which is based on the dependence of the oxide etch rate on rf power is proposed.
Liquid helium cryopumps with low-emissivity Al film coatings and low helium consumption
Authors: Gotoh Nobuaki , Momose Takashi , Ishimaru Hajime , Larin M. P.
Published: July 2002

Liquid helium storage-type cryopumps made in Russia with a special surface treatment were experimentally studied. Pressures of the order of 10−9 Pa were obtained 19.5 h after the pump was filled with liquid helium. The ultimate pressure obtained was 2×10−10 Pa, with no baking, after about 58 days. The temperature of the cryosurface was 4.2 K. The evaporation rate of liquid helium was 8.7×10−10 m3/s (3.1 ml/h). The volume for liquid helium in the pump is about 7 ℓ. The total inner surface area of the cryopump is about 0.23 m2. The Al film coating has an emissivity of 2×10−3 for liquid helium temperature to liquid nitrogen temperature. Its grain size is 2 to 3 μm, with a thickness of no less than 1 μm and a roughness of about 0.16 μm. The 7 ℓ of liquid helium lasted for about three months.
Substrate effects in cubic boron nitride film formation
Authors: Mirkarimi P. B. , McCarty K. F. , Cardinale G. F. , Medlin D. L. , Ottesen D. K. , Johnsen H. A.
Published: July 2002

We have examined the effect of the substrate in cubic boron nitride (c-BN) film synthesis by depositing BN films on a variety of materials using ion-assisted pulsed laser deposition. Using optical modeling, we estimated the c-BN content of the films from the measured infrared reflectance spectra. We find less c-BN in films grown on metal substrates than in films grown on Si and SiC/Si substrates. The c-BN content of the films decreased with decreasing substrate microhardness. This result is qualitatively consistent with the model of stress-induced c-BN film formation.
Reactive ion etching of GaN and GaAs: Radially uniform processes for rectangular, smooth sidewalls
Authors: Franz Gerhard , Rinner Franz
Published: July 2002

Vertical and smooth cutting of GaN has been demonstrated applying reactive ion etching (RIE) in capacitively coupled plasmas using parallel-plate reactors (common RIE) and in plasmas driven by electron cyclotron resonance (ECR). The radial uniformity across 50 mm (2 in.) is no issue in ECR-driven plasmas and can be effectively improved in parallel-plate reactors by using shower heads with one central hole only, provided the wafer is centrally placed.
Epitaxial growth of elemental semiconductor films onto silicide/Si and fluoride/Si structures
Authors: Ishiwara H. , Asano T. , Furukawa S.
Published: July 2002

Epitaxial growth of Si and Ge films onto silicide/Si and fluoride/Si structures has been reviewed. Growth conditions of epitaxial silicide films such as Pd2Si, CoSi2, and NiSi2 films on Si substrates, as well as heteroepitaxial Si/CoSi2/Si structures, are presented. Crystalline quality and structural properties of the films have been analyzed by Rutherford backscattering and channeling spectroscopy, transmission electron microscopy, optical microscopy, and x-ray diffraction analysis. Growth conditions of fluoride films such as CaF2, SrF2, and BaF2 films on Si substrates are also presented. For the growth of Si and Ge overlayers on the fluoride/Si structure, the lattice matching condition between the semiconductor and fluoride films has approximately been satisfied by use of pure and mixed fluoride films.
Theoretical investigations of the nature of the normal and inverted GaAs–AlGaAs structures grown by molecular beam epitaxy
Authors: Singh Jasprit , Bajaj K. K.
Published: July 2002

We have developed an atomistic model for the growth of GaAs and AlGaAs and have simulated the MBE growth of both the normal (AlGaAs on GaAs) and the inverted (GaAs on AlGaAs) structures along (100) direction using Monte Carlo techniques. We assume the growth to occur under anion overpressure with As2 molecular species as the anion source and Ga and Al atoms as the cation sources. We find that some of the differences in the quality of the two interfaces can be explained on the basis of the surface kinetics operational for the two kinds of cations. In our model there is a considerable interlayer surface migration for the Ga atoms due to the relatively weak Ga–As bond compared to the Al–As bond. For comparable substrate temperatures the stronger Al–As bonds lower the interlayer diffusion for Al atoms. The role of this key kinetic step, namely, the interlayer surface migration on the quality of the growth front profiles of GaAs and AlGaAs as well as their interfaces is examined.
GaAs growth in metal–organic MBE
Authors: Pütz N. , Veuhoff E. , Heinecke H. , Heyen M. , Lüth H. , Balk P.
Published: July 2002

In this paper we report on the growth of GaAs in a UHV system from molecular beams of trimethyl gallium (TMG) and arsine (AsH3). Deposition could only be achieved if the AsH3 was partially decomposed before injecting it into the system. If arsenic is provided in excess, the growth rate depends linearly on the TMG beam pressure. The growth rate saturates the system if the arsenic pressure in the beam is reduced; the saturation value being proportional to the arsenic flux. The results can be explained by a model assuming that sticking of TMG at the growing surface is allowed only if As simultaneously is supplied in excess. The layers are heavily doped with carbon ( p≊1019–1020 cm−3). The carbon uptake is reduced by several orders of magnitude if TEG is used rather than TMG.
Properties of titanium silicide films deposited by plasma-enhanced chemical vapor deposition
Authors: Hemmes Diederik G.
Published: July 2002

Titanium silicide is a desirable interconnect material for future very large scale integrated circuit (VLSI) devices because of its low resistivity (15 μΩ cm) and because of its low sinter temperature (600 °C) compared to other refractory metal silicides. Chemical vapor deposited (CVD) films have much better purity and step coverage than the conventional physical vapor deposited (PVD) films. A study has been made of titanium silicide deposited by plasma-enhanced CVD (PECVD). Rutherford backscattering has been used to analyze the dependence of the as-deposited film composition on the process parameters. The changes in the composition and the resistivity of the films during both furnace and rapid thermal anneals have been studied. It has been shown that it is possible to grow a SiO2 layer on top of the silicide film when a proper clean of the substrate surface is done before the deposition. Stress levels after anneal are about 1×1010 dyn/cm2. Anisotropic etch of the film is possible even when deposited on a polysilicon substrate.
Electrical properties and applications of InxAl1−xAs/InP
Authors: Hanson C. M. , Wieder H. H.
Published: July 2002

Prototype depletion mode heterojunction-insulated gate field-effect transistors using In0.43Al0.57As as a quasigate insulator were fabricated and their low-frequency properties were evaluated. Typical extrinsic transconductances of gm=20 mS/mm were obtained for devices with gate length of 6 μm which exhibited no direct current drain current instabilities. A qualitative fit to a metal–insulator field-effect transistor (MISFET) model was obtained using the material parameters of the InP and In0.43Al0.57As epilayers and assuming that this quasi-insulator could be represented as a conventional insulator. The equilibrium surface potential has been determined to be −0.05 eV. Capacitance–voltage (C–V) and conductance-frequency measurements made on similar heterojunction capacitors show that the maximum interface state density is in the low 1011/cm2 eV range and confirm the slight depletion of the InP surface.
Multicomponent Langmuir–Blodgett resists for optical lithography
Authors: Kosbar Laura L. , Frank Curtis W. , Pease R. Fabian W.
Published: July 2002

We have used Langmuir–Blodgett (LB) techniques to prepare very thin (≤1000 Å), uniform organic films, and we have investigated their potential use in lithographic applications. Resist films were prepared using novolac and poly (p-hydroxystyrene) resins and both near and deep UV sensitive photoactive compounds (PAC). LB resist films formed from mixtures of polymer and PAC behaved lithographically in a similar fashion to spin cast films. LB films as thin as 300 Å were sufficient to protect 500 Å of chromium during wet chemical etching. As few as three monolayers of PAC deposited on the top surface of a spin cast novolac film was sufficient to protect up to ∼1 μm of film from dissolving. Investigation of the ‘‘sphere of influence’’ of PAC molecules by controlling their distribution throughout the film indicates that strong interactions may exist between consecutive LB layers of PAC.
Scanning tunneling microscopy investigation of stabilized Au55 clusters
Authors: Becker C. , Fries Th. , Wandelt K. , Kreibig U. , Schmid G.
Published: July 2002

Au55 clusters stabilized by phosphine {Au55[(C6H5)3P]12Cl6 and Au55(C6H5)2PC6H4SO3Na]12Cl6} [K. Fauth, U. Kreibig, and G. Schmid, Z. Phys. D 12, 515 (1989)] were deposited onto highly oriented pyrolytic graphite (HOPG) and investigated in air by STM in the constant current mode. Single Au55 clusters as well as aggregates could be distinguished. Our images clearly differ from those of free (non-stabilized) metal clusters [E. Ganz, K. Sattler, and J. Clark, Surf. Sci. 219, 33 (1989)]. This is explained in terms of the low conductivity of the phosphine layer which is chemically bonded to the gold surface rather strongly. The single Au55 clusters appear to have a diameter of about 22 Å (including the ligand shell) and seem to be very floppy.
Aluminum on Si(100): Growth and structure of the first layer
Authors: Brocks G. , Kelly P. J. , Car R.
Published: July 2002

The growth and the (electronic) structure of a single layer of aluminum on the Si(100) surface are examined by means of first principles calculations. The calculated local density of states is used to interprete scanning tunneling microscopy data. We identify the adsorption sites that give rise to the polymerization-like one-dimensional growth of Al. The Al-induced surface states of the p(2×2) covered Si(100) surface are calculated. The surface bandgap is increased, as compared to the clean Si(100) surface, which means that the first adsorbed Al layer passivates the surface electrically.
Oxidation of silicon (100): Experimental data versus a unified chemical model
Authors: Thanikasalam P. , Whidden T. K. , Ferry D. K.
Published: July 2002

It has been observed in many studies of oxidation kinetics that silicon dioxide growth in the thin regime (<30 nm) is faster than the predictions of the linear-parabolic Deal–Grove relationship. We have developed a conceptual and mathematical model for the thermal oxidation of silicon which is based on an initial dissociative chemisorption of molecular oxygen on the 2×1 silicon (100) surface followed by subsequent diffusion and dissociative reactions of molecular oxygen at the Si/SiO2 interface. This model accounts for current experimental observations on the structural modification of the reconstructed surface to a 1×1 superlattice on limited exposure to molecular oxygen and provides a mechanistic rationale for the self-limiting mechanism of the oxide film at ∼0.6 nm during low-temperature oxidation processes. The rate-equation model, consistent with the proposed reactions at the Si/SiO2 interface, has been refined to give an excellent fit to experimental data within all thickness regimes, but especially in the initial rapid growth regime where the growth rate is proportional to (PO2)1/2. The rate equation reduces to a linear dependence on oxygen partial pressure in the thicker regime, where it predicts classic Deal–Grove behavior. We present the development of the model for oxidations performed between 780–1100 °C consistent with observed oxide growth and film properties. The activation energies for the reaction-controlled regime and the diffusion-controlled regime are consistent with literature data. We observe a sharp transition in a characteristic length parameter at ∼950 °C which may be possibly due to the experimentally observed change in oxide film density. A detailed analysis and explanation is presented.
New optoelectronic tip design for ultrafast scanning tunneling microscopy
Authors: Groeneveld R. H. M. , Rasing Th. , Kaufmann L. M. F. , Smalbrugge E. , Wolter J. H. , Melloch M. R. , van Kempen H.
Published: July 2002

We have developed a scanning tunneling microscope using an optoelectronic switch that gates the tunneling tip current. The switch is fabricated within 30 μm from the tip by photolithography and an accurate cleavage method. We demonstrate this approach by detecting picosecond electrical transients on a coplanar stripline. We have investigated the signal dependence on contact resistance and found significant differences when the tip is brought from low-ohmic contact into the tunneling regime. In this regime, the THz signal amplitude was found to depend linearly on the tunnel conductance, and disappeared when the tip was retracted.
Regular array of Si nanopillars fabricated using metal clusters
Authors: Tada Tetsuya , Kanayama Toshihiko
Published: July 2002

We have developed a fabrication process of Si nanopillars using metal clusters arranged by electron beam (e-beam) lithography. This process forms nanopillars by taking advantage of the fact that metal clusters deposited on Si substrates act as nuclei for self-formation of etch masks during electron cyclotron plasma etching with SF6 if the substrate is kept at ∼−135 °C. The clusters are placed on the substrate by an e-beam lift-off technique following a small amount of deposition of metal vapors. Arrays of Si pillars with a regular spacing of 100 nm were actually fabricated using Au, Ag, and Fe clusters. Au clusters yielded 70 nm high pillars with an average diameter of 10 nm and a standard deviation of 1.3 nm, which is exceedingly better than the resolution of the lithography used (∼30 nm). Ag and Fe clusters produced pillars 20 nm in diameter. These results demonstrate that the pillar size is controlled by species of the metal clusters, whereas the position is defined by the e-beam lithography. We have also found that Fe clusters are very durable in the etching process and can produce pillars with a very high aspect ratio: 280 nm high and 20 nm in diameter.
Costs and the Diversification of Exaggerated Animal Structures
Authors: Emlen Douglas J.
Published: July 2002

Sexual selection can favor production of extravagant ornaments and weapons in the contest for access to the opposite sex. Existing explanations for the diversity of sexually selected structures focus on reproductive benefits conferred by particular ornament or weapon morphologies. Here, I show that costs of weapon production also may drive patterns of weapon evolution. In beetles, production of horns reduces the size of neighboring morphological structures (antennae, eyes, or wings, depending on the location of the horns), and these tradeoffs reveal unexpected functional associations between ecology and horn morphology. This study illustrates a critical but overlooked role of costs in sexual selection and has implications for understanding the evolution of animal morphology.
Seasonal Variations of Snow Depth on Mars
Authors: Smith David E. , Zuber Maria T. , Neumann Gregory A.
Published: July 2002

Using topography collected over one martian year from the Mars Orbiter Laser Altimeter on the Mars Global Surveyor (MGS) spacecraft, we have measured temporal changes in the elevation of the martian surface that correlate with the seasonal cycle of carbon dioxide exchange between the surface and atmosphere. The greatest elevation change (1.5 to 2 meters) occurs at high latitudes ( above 80°), whereas the bulk of the mass exchange occurs at lower latitudes (below 75° N and below 73° S). An unexpected period of sublimation was observed during northern hemisphere autumn, coincident with dust storms in the southern hemisphere. Analysis of MGS Doppler tracking residuals revealed temporal variations in the flattening of Mars that correlate with elevation changes. The combined changes in gravity and elevation constrain the average density of seasonally deposited carbon dioxide to be 910 ± 230 kilograms per cubic meter, which is considerably denser than terrestrial snow.
The Clearest View: Hubble Telescope to Get an Upgrade
Authors: Vogel Gretchen
Published: July 2002

On 14 February, space-walking astronauts will put two new instruments into the orbiting Hubble Space Telescope—and thereby quicken the pace of astronomical discovery. If all goes as planned, Hubble's gaze will be able to encompass hundreds of objects at once, thanks to instruments called NICMOS (Near Infrared Camera and Multi-Object Spectrometer) and STIS (Space Telescope Imaging Spectrograph).
Areal Segregation of Face-Processing Neurons in Prefrontal Cortex
Authors: Ó Scalaidhe Séamas P. , Wilson Fraser A. W. , Goldman-Rakic Patricia S.
Published: July 2002

A central issue in cognitive neuroscience concerns the functional architecture of the prefrontal cortex and the degree to which it is organized by sensory domain. To examine this issue, multiple areas of the macaque monkey prefrontal cortex were mapped for selective responses to visual stimuli that are prototypical of the brain's object vision pathway—pictorial representations of faces. Prefrontal neurons not only selectively process information related to the identity of faces but, importantly, such neurons are localized to a remarkably restricted area. These findings suggest that the prefrontal cortex is functionally compartmentalized with respect to the nature of its inputs.
Ca
2+
Flux Through Promiscuous Cardiac Na
+
Channels: Slip-Mode Conductance
Authors: Santana L. F. , Gómez A. M. , Lederer W. J.
Published: July 2002

The tetrodotoxin-sensitive sodium ion (Na
+
) channel is opened by cellular depolarization and favors the passage of Na
+
over other ions. Activation of the β-adrenergic receptor or protein kinase A in rat heart cells transformed this Na
+
channel into one that is promiscuous with respect to ion selectivity, permitting calcium ions (Ca
2+
) to permeate as readily as Na
+
. Similarly, nanomolar concentrations of cardiotonic steroids such as ouabain and digoxin switched the ion selectivity of the Na
+
channel to this state of promiscuous permeability called slip-mode conductance. Slip-mode conductance of the Na
+
channel can contribute significantly to local and global cardiac Ca
2+
signaling and may be a general signaling mechanism in excitable cells.
Variations in Atmospheric N
2
O Concentration During Abrupt Climatic Changes
Authors: Flückiger J. , Dällenbach A. , Blunier T. , Stauffer B. , Stocker T. F. , Raynaud D. , Barnola J.-M.
Published: July 2002

Nitrous oxide (N
2
O) is an important greenhouse gas that is presently increasing at a rate of 0.25 percent per year. Records measured along two ice cores from Summit in Central Greenland provide information about variations in atmospheric N
2
O concentration in the past. The record covering the past millennium reduces the uncertainty regarding the preindustrial concentration. Records covering the last glacial-interglacial transition and a fast climatic change during the last ice age show that the N
2
O concentration changed in parallel with fast temperature variations in the Northern Hemisphere. This provides important information about the response of the environment to global climatic changes.
Chunk Versus Point Sampling: Visual Imaging in a Small Insect
Authors: Buschbeck Elke , Ehmer Birgit , Hoy Ron
Published: July 2002

The eyes of strepsipteran insects are very unusual among living insects. In their anatomical organization they may form a modern counterpart to the structural plan proposed for the eyes of some trilobites. Externally they differ from the usual “insect plan” by presenting far fewer but much larger lenses. Beneath each lens is its own independent retina. Anatomical and optical measurements indicate that each of these units is image-forming, so that the visual field is subdivided into and represented by “chunks,” unlike the conventional insect compound eye that decomposes the visual image in a pointwise manner. This results in profound changes in the neural centers for vision and implies major evolutionary changes.
Titanium Carbide Nanocrystals in Circumstellar Environments
Authors: Helden G. von , M. A. G. G. , Tielens  , Heijnsbergen D. van , Duncan M. A. , Hony S. , Waters L. B. F. M. , Meijer G.
Published: July 2002

Meteorites contain micrometer-sized graphite grains with embedded titanium carbide grains. Although isotopic analysis identifies asymptotic giant branch stars as the birth sites of these grains, there is no direct observational identification of these grains in astronomical sources. We report that infrared wavelength spectra of gas-phase titanium carbide nanocrystals derived in the laboratory show a prominent feature at a wavelength of 20.1 micrometers, which compares well to a similar feature in observed spectra of postasymptotic giant branch stars. It is concluded that titanium carbide forms during a short (approximately 100 years) phase of catastrophic mass loss (>0.001 solar masses per year) in dying, low-mass stars.
Efficacies of Two New Antifungal Agents, the Triazole Ravuconazole and the Echinocandin LY-303366, in an Experimental Model of Invasive Aspergillosis
Authors: Roberts Jenna , Schock Kathleen , Marino Susan , Andriole Vincent T.
Published: July 2002

The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge. Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated
Aspergillus fumigatus
organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis. Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment. Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B. Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.
Efficacy of the Cyclodextrin Liquid Preparation of Itraconazole in Treatment of Denture Stomatitis: Comparison with Itraconazole Capsules
Authors: Cross L. J. , Bagg J. , Aitchison T. C.
Published: July 2002

This study investigated the efficacy of a cyclodextrin solution of itraconazole in the treatment of
Candida
-associated denture stomatitis. It was found that the liquid and capsule preparations of itraconazole were equally effective adjuncts in the treatment of this condition. However, the side effect profile indicates that capsules are the preferred formulation.
Antibacterial Efficacy of Gentamicin Encapsulated in pH-Sensitive Liposomes against an In Vivo
Salmonella enterica
Serovar Typhimurium Intracellular Infection Model
Authors: Cordeiro Carol , Wiseman David J. , Lutwyche Peter , Uh Mitchell , Evans Jennifer C. , Finlay B. Brett , Webb Murray S.
Published: July 2002

Encapsulation of gentamicin in liposomes can be used to achieve intracellular delivery and broaden the clinical utility of this drug. We have previously described a novel, rationally designed, pH-sensitive liposomal carrier for gentamicin that has superior in vitro efficacy against intracellular infections compared to the efficacies of both free gentamicin and non-pH-sensitive liposomal controls. This liposomal carrier demonstrated pH-sensitive fusion that was dependent on the presence of unsaturated phosphatidylethanolamine (PE) and the pH-sensitive lipid
N
-succinyldioleoyl-PE. The pharmacokinetics and biodistribution of the free and liposomal gentamicin were examined in mice bearing a systemic
Salmonella enterica
serovar Typhimurium infection. Encapsulation of gentamicin in pH-sensitive liposomes significantly increased the concentrations of the drug in plasma compared to those of free gentamicin. Furthermore, the levels of accumulation of drug in the infected liver and spleen were increased by 153- and 437-fold, respectively, as a result of liposomal encapsulation. The increased accumulation of gentamicin in the liver and spleen effected by liposomal delivery was associated with 10
4
-fold greater antibacterial activity than that associated with free gentamicin in a murine salmonellosis model. These pH-sensitive liposomal antibiotic carriers with enhanced in vitro activity could be used to improve both in vivo intracellular drug delivery and biological activity.
Assignment of the Substrate-Selective Subunits of the MexEF-OprN Multidrug Efflux Pump of
Pseudomonas aeruginosa
Authors: Maseda Hideaki , Yoneyama Hiroshi , Nakae Taiji
Published: July 2002

Pseudomonas aeruginosa
expresses a low level of the MexAB-OprM efflux pump and shows natural resistance to many structurally and functionally diverse antibiotics. The mutation that has been referred to previously as
nfxC
expresses an additional efflux pump, MexEF-OprN, exhibiting resistance to fluoroquinolones, imipenem, and chloramphenicol and hypersusceptibility to β-lactam antibiotics. To address the antibiotic specificity of the MexEF-OprN efflux pump, we introduced a plasmid carrying the
mexEF-oprN
operon into
P. aeruginosa
lacking the
mexAB-oprM
operon. The transformants exhibited resistance to fluoroquinolones, trimethoprim, and chloramphenicol but, unlike most
nfxC
-type mutants, did not show β-lactam hypersusceptibility. The transformants exhibited additional resistance to tetracycline. In the next experiment, we analyzed the MexEF-OprN pump subunit(s) responsible for substrate selectivity by expressing MexE, MexF, OprN, and MexEF in strains lacking MexA, MexB, OprM, and MexAB, respectively. The MexEF-OprM/ΔMexAB transformants exhibited MexEF-OprN-type pump function that rendered the strains resistant to fluoroquinolones and chloramphenicol but did not change susceptibility to β-lactam antibiotics compared with the host strain. The MexAB-OprN/ΔOprM, MexAF-OprM/ΔMexB, and MexEB-OprM/ΔMexA mutants exhibited antibiotic susceptibility indistinguishable from that in the mutant lacking both types of efflux pumps. The results imply that the MexEF-OprM pump selects substrates by a MexEF functional unit. Interestingly, OprN did not link functionally with the MexAB complex, despite the fact that OprM interacted functionally with MexEF.
Evidence for Active Efflux as the Primary Mechanism of Resistance to Ciprofloxacin in
Salmonella enterica
Serovar Typhimurium
Authors: Giraud Etienne , Cloeckaert Axel , Kerboeuf Dominique , Chaslus-Dancla Elisabeth
Published: July 2002

The occurrence of active efflux and cell wall modifications were studied in
Salmonella enterica
serovar Typhimurium mutants that were selected with enrofloxacin and whose phenotypes of resistance to fluoroquinolones could not be explained only by mutations in the genes coding for gyrase or topoisomerase IV. Mutant BN18/21 exhibited a decreased susceptibility to ciprofloxacin (MIC = 0.125 μg/ml) but did not have a mutation in the
gyrA
gene. Mutants BN18/41 and BN18/71 had the same substitution, Gly81Cys in GyrA, but exhibited different levels of resistance to ciprofloxacin (MICs = 2 and 8 μg/ml, respectively). None of the mutants had mutations in the
parC
gene. Evidence for active efflux was provided by a classical fluorimetric method, which revealed a three- to fourfold decrease in ciprofloxacin accumulation in the three mutants compared to that in the parent strain, which was annuled by addition of the efflux pump inhibitor carbonyl cyanide
m
-chlorophenylhydrazone. In mutant BN18/71, a second fluorimetric method also showed a 50% reduction in the level of accumulation of ethidium bromide, a known efflux pump substrate. Immunoblotting and enzyme-linked immunosorbent assay experiments with an anti-AcrA antibody revealed that the resistance phenotype was strongly correlated with the expression level of the AcrAB efflux pump and suggested that decreased susceptibility to ciprofloxacin due to active efflux probably related to overproduction of this pump could occur before that due to
gyrA
mutations. Alterations were also found in the outer membrane protein and lipopolysaccharide profiles of the mutants, and these alterations were possibly responsible for the decrease in the permeability of the outer membrane that was observed in the mutants and that could act synergistically with active efflux to decrease the level of ciprofloxacin accumulation.
In Vitro Pharmacodynamics of the New Ketolides HMR 3004 and HMR 3647 (Telithromycin) against
Chlamydia pneumoniae
Authors: Gustafsson I. , Hjelm E. , Cars O.
Published: July 2002

The ketolides HMR 3004 and HMR 3647 (telithromycin) are a new class of macrolides that have a potential clinical efficacy against intracellular pathogens. The objectives of this study were to investigate the MIC, minimum bactericidal concentration, and time-dependent killing of two
Chlamydia pneumoniae
strains of the two ketolides. The killing effect was also studied with a newly developed intracellular in vitro kinetic model. Furthermore, HMR 3647 was studied for the effect of a subinhibitory concentration of 0.5 times the MIC after a preexposure of 10 times the MIC during 12 h. The MICs for both strains were 0.0039 and 0.0156 mg/liter for HMR 3004 and HMR 3647, respectively. Killing with 10 times the MIC was time dependent, increasing from a 1-log-unit decrease in the number of inclusions per well at 48 h to a maximal effect of 2.8-log-unit decrease after 96 h. A preexposure of 10 times the MIC of HMR 3647 for 12 h followed by a subinhibitory concentration of 0.5 times the MIC increased the killing effect to a 1.2-log-unit reduction in inclusions per well. An exposure for 12 h gave poor reduction of inclusions, while a static dose of 10 times the MIC for 72 h showed a 2.2-log-unit reduction in inclusions per well. In the kinetic model, a small number of inclusions were detected after 72 h by one exposure of 10 times the MIC. Regrowth could not be detected after 120 h. The ketolides HMR 3004 and HMR 3647 have bactericidal activity and show a significant sub-MIC effect on the intracellular pathogen
C. pneumoniae
.
Efficacies of Moxifloxacin, Ciprofloxacin, and Vancomycin against Experimental Endocarditis Due to Methicillin-Resistant
Staphylococcus aureus
Expressing Various Degrees of Ciprofloxacin Resistance
Authors: Entenza J. M. , Que Y. A. , Vouillamoz J. , Glauser M. P. , Moreillon P.
Published: July 2002

The new 8-methoxyquinolone moxifloxacin was tested against two ciprofloxacin-susceptible
Staphylococcus aureus
strains (strains P8 and COL) and two ciprofloxacin-resistant derivatives of strain P8 carrying a single
grlA
mutation (strain P8-4) and double
grlA
and
gyrA
mutations (strain P8-128). All strains were resistant to methicillin. The MICs of ciprofloxacin and moxifloxacin were 0.5 and 0.125 mg/liter, respectively, for P8; 0.25 and 0.125 mg/liter, respectively, for COL; 8 and 0.25 mg/liter, respectively, for P8-4; and ≥128 and 2 mg/liter, respectively, for P8-128. In vitro, the rate of spontaneous resistance of P8 and COL was 10
−7
on agar plates containing ciprofloxacin at two times the MIC, whereas it was ≤10
−10
on agar plates containing moxifloxacin at two times the MIC. Rats with experimental aortic endocarditis were treated with doses of drugs that simulate the kinetics in humans: moxifloxacin, 400 mg orally once a day; ciprofloxacin, 750 mg orally twice a day; or vancomycin, 1 g intravenously twice a day. Treatment was started either 12 or 24 h after infection and lasted for 3 days. Moxifloxacin treatment resulted in culture-negative vegetations in a total of 20 of 21 (95%) rats infected with P8, 10 of 11 (91%) rats infected with COL, and 19 of 24 (79%) rats infected with P8-4 (
P
< 0.05 compared to the results for the controls). In contrast, ciprofloxacin treatment sterilized zero of nine (0%) vegetations infected with first-level resistant mutant P8-4. Vancomycin sterilized only 8 of 15 (53%), 6 of 11 (54%), and 12 of 23 (52%) of the vegetations, respectively. No moxifloxacin-resistant derivative emerged among these organisms. However, moxifloxacin treatment of highly ciprofloxacin-resistant mutant P8-128 failed and selected for variants for which the MIC increased two times in 2 of 10 animals. Thus, while oral moxifloxacin might deserve consideration as treatment for staphylococcal infections in humans, caution related to its use against strains for which MICs are borderline is warranted.
In Vitro Activity of PNU-100766 (Linezolid), a New Oxazolidinone Antimicrobial, against
Nocardia brasiliensis
Authors: Vera-Cabrera Lucio , Gómez-Flores Alejandra , Escalante-Fuentes Wendy G. , Welsh Oliverio
Published: July 2002

The in vitro activity of a novel oxazolidinone, linezolid, was studied by comparing the activity of linezolid with those of amikacin, trimethoprim-sulfamethoxazole, and amoxicillin-clavulanic acid against 25 strains of
Nocardia brasiliensis
isolated from patients with mycetoma. All
N. brasiliensis
strains tested were sensitive to linezolid (MIC at which 90% of strains are inhibited [MIC
90
], 2 μg/ml; MIC
50
, 1 μg/ml). This antimicrobial might constitute a good alternative for treatment of actinomycetoma.
Susceptibility Testing of
Aspergillus flavus
: Inoculum Dependence with Itraconazole and Lack of Correlation between Susceptibility to Amphotericin B In Vitro and Outcome In Vivo
Authors: Mosquera J. , Warn P. A. , Morrissey J. , Moore C. B. , Gil-Lamaignere C. , Denning D. W.
Published: July 2002

We have attempted to validate in
Aspergillus flavus
the main in vitro methodologies that have been used to detect resistance in
Aspergillus fumigatus
. We developed a murine model with two
A. flavus
isolates, one that was apparently resistant in vitro to amphotericin B (AFL5) and another that was resistant to itraconazole (AFL8). No correlation was found for amphotericin B in AFL5, since the in vivo response was compatible with a susceptible isolate. Modification of the in vitro susceptibility test methodology for amphotericin B was unsuccessful. Although AFL8 was apparently resistant to itraconazole in vitro, it was found to be susceptible in vivo. Additional in vitro work has detected weaknesses in the in vitro susceptibility methodology validated for
A. fumigatus
when applied to
A. flavus
. The principal problems are that changes in the inoculum have a large effect on the MICs of itraconazole for some
A. flavus
strains and that a trailing end point and spore sediment often appear when an inoculum with a higher colony count is used. We propose a modified method using a final inoculum of 2.5 × 10
4
CFU per ml of RPMI 1640 medium with 2% glucose buffered to pH 7.0 in a microtiter format, incubated for 48 h with no growth end point. Validation of this methodology requires one or more itraconazole-resistant
A. flavus
isolates, which have yet to be identified.
RFI-641, a Potent Respiratory Syncytial Virus Inhibitor
Authors: Huntley Clayton C. , Weiss William J. , Gazumyan Anna , Buklan Aron , Feld Boris , Hu William , Jones Thomas R. , Murphy Timothy , Nikitenko Antonia A. , O'Hara Bryan , Prince Gregory , Quartuccio Susan , Raifeld Yuri E. , Wyde Philip , O'Connell John F.
Published: July 2002

Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that the antiviral activity of the compound is not due to adverse effects on normal cells. The potent in vitro activity of RFI-641 can be translated to efficacy in vivo: RFI-641 is efficacious when administered prophylactically by the intranasal route in mice, cotton rats, and African green monkeys. RFI-641 is also efficacious when administered therapeutically (24 h postinfection) in the monkey model. Mechanism of action studies indicate that RFI-641 blocks viral F protein-mediated fusion and cell syncytium formation.
Survival and Epiphytic Fitness of a Nonpathogenic Mutant of
Xanthomonas campestris
pv. Glycines
Authors: Rukayadi Yaya , Suwanto Antonius , Tjahjono Budi , Harling Rob
Published: July 2002

Xanthomonas campestris
pv. glycines is the causal agent of bacterial pustule disease of soybeans. The objective of this work was to construct a nonpathogenic mutant derived from the pathogenic wild-type strain YR32 and to evaluate its effectiveness in preventing growth of its parent on the soybean phyllosphere. A mini-Tn
5
-derived transposon was used to generate nonpathogenic mutants. Southern hybridization and pulsed-field gel electrophoresis confirmed the presence of a single transposon in each of the nonpathogenic mutants. One of the nonpathogenic mutants, M715, failed to induce a hypersensitive response in tomato leaves. An ice nucleation gene (
inaZ
) carried in pJL1703 was introduced into strain YR32 as a reporter gene to demonstrate that the presence of M715 could reduce colonization of the soybean phyllosphere by YR32. de Wit serial replacement analysis showed that M715 competed equally with its wild-type parental strain, YR32. Epiphytic fitness analysis of YR32 in the greenhouse indicated that the population dynamics of strains YR32, YR32(pJL1703), and M715 were similar, although the density of the mutant was slightly less than that of its parent. The M715 mutant was able to survive for 16 days after inoculation on soybean leaves and maintained population densities of approximately 10
4
to 10
5
cells g (fresh weight) of leaf
−1
. Therefore, M715 shows promise as an effective biocontrol agent for bacterial pustule disease in soybeans.