bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of sidewall roughness during dry etching of SiO2
Authors: Ren F. , Pearton S. J. , Lothian J. R. , Abernathy C. R. , Hobson W. S.
Published: July 2002

The appearance of striations on dry etched semiconductor laser mesas is a common feature of these structures. We describe a number of different methods of reducing the extent of this roughness, including the choice of dielectric etch chemistry, modification of the initial resist processing, and deposition of a SiN sidewall to prevent additional roughening during the plasma etch step. SF6 is found to be preferable to CF4 for dielectric etching because of an absence of polymer formation. This produces smoother SiO2 sidewalls. Flood exposure of theinitial photoresist mask and optimization of the postbake temperature also produces smoother sidewalls on the subsequently etched SiO2. The sidewall can also be protected from roughening that occurs during the dry etch step by coating it with a low temperature SiN layer. A combination of all of these methods produces sidewalls with morphological variations of ≤500 Å.
Properties of silicon dioxide films deposited at low temperatures by microwave plasma enhanced decomposition of tetraethylorthosilicate
Authors: Ray S. K. , Maiti C. K. , Lahiri S. K. , Chakrabarti N. B.
Published: July 2002

Silicon dioxide films have been deposited at low temperatures (200–250 °C) by microwave plasma enhanced decomposition of tetraethylorthosilicate (TEOS). The effects of the presence of oxygen in the discharge in film deposition rate, mechanism, and the physical properties of the films have been investigated. Structural characterization of the deposited films has been carried out by etch rate measurements, infrared transmission spectra, x-ray photoelectron spectroscopy, Auger, and secondary ion mass spectrometry analyses. Films deposited using TEOS and oxygen have confirmed a density comparable to standard silane-based low-pressure chemical vapor deposition and plasma enhanced chemical vapor deposition oxides, nearly perfect stoichiometry, extremely low sodium and carbon content, and the absence of many undesirable hydrogen related bonds. Various electrical properties, viz., resistivity, breakdown strength, fixed oxide charge density, interface state density, and trapping behavior have been evaluated by the characterization of metal–oxide semiconductor capacitors fabricated using deposited oxides. Deposited films on thin native oxides grown by either in situ plasma oxidation or a low temperature thermal oxidation exhibited excellent electrical properties.
Multiple beam-shaping diaphragm for efficient exposure of gratings
Authors: Elsner H. , Hahmann P. , Dahm G. , Koops H. W. P.
Published: July 2002

The variable-shaped beam principle has some advantages over Gaussian beams in terms of throughput. The multiple beam-shaping diaphragm concept offers additional capabilities and further increase of throughput. The fabrication procedure of the diaphragm blades are described. We used the multiple beam-shaping diaphragm in ZBA 31/32 from JENOPTIK for efficient exposure of gratings with critical dimension down to 150 nm.
Applications of an atomic force microscope voltage probe with ultrafast time resolution
Authors: Nechay B. A. , Ho F. , Hou A. S. , Bloom D. M.
Published: July 2002

Although scanning probe microscopy is traditionally limited to slow temporal response, techniques utilizing nonlinear tip-to-sample interactions can be used to capture very fast temporal signals. We have developed a scanning force microscope probe which makes use of these techniques for measuring ultrafast voltage signals with both picosecond time resolution and nanometer-scale lateral resolution. Measurements of very large scale integrated and microwave integrated circuits are shown.
High-frequency pattern extraction in digital integrated circuits using scanning electrostatic force microscopy
Authors: Bridges G. E. , Said R. A. , Mittal M. , Thomson D. J.
Published: July 2002

The ability to perform noninvasive logic analysis at the internal points of integrated circuits is crucial in the design and test of advanced microelectronics. We present a noncontact scanning probe technique for extracting high-frequency digital patterns at internal points of an integrated circuit. The digital waveforms are determined by sensing the localized electrostatic force between a small probe and point on the circuit being measured. The force is monitored by detecting the deflection of the probe using a fiber-optic interferometer. The bandwidth of force measurements made using proximal probes are typically limited by the mechanical frequency response of the probe. In the presented instrument high-frequency bit-by-bit digital pattern measurements are enabled by using a pulse sampled heterodyne technique. In conjunction with a nulling approach, the technique is capable of measurements without complex calibration or probe positioning, and can be performed over passivated structures. A simple procedure is also presented which corrects errors due to nonidealities of the pulse sampling waveform. Using a probe with a kHz resonant frequency, Mbit/s patterns have been measured. Errors due to coupling from adjacent signal lines and due to surface charge effects are examined.
Growth of GaxIn1−xAs quantum wire heterostructures by the strain-induced lateral-layer ordering process
Authors: Chou S. T. , Hsieh K. C. , Cheng K. Y. , Chou L. J.
Published: July 2002

GaxIn1−xAs quantum wire (QWR) arrays were grown in situ by molecular beam epitaxy. A lateral composition modulation was achieved in the GaxIn1−xAs material system via the strain-induced lateral layer ordering process occurring spontaneously when (GaAs)n/(InAs)n short-period superlattices are grown on (100)-oriented on-axis InP substrates. The resulting quasiperiodic modulation of the GaxIn1−xAs composition, with a periodicity of 300 Å, offers a lateral quantum confinement along the growth plane. The quantum confinement in the growth direction is provided by sandwiching the thin (∼100 Å) laterally ordered GaxIn1−xAs layer between layers of bulk Al0.24Ga0.24In0.52As. The formation of the QWR array is confirmed by cross-sectional transmission electron microscopy and polarized photoluminescence measurements.
Field emission from silicon spikes with diamond coatings
Authors: Zhirnov V. V. , Givargizov E. I. , Plekhanov P. S.
Published: July 2002

Diamond-coated silicon field emitters were fabricated and investigated. Emission currents of few μA per tip at voltages of several hundred volts were obtained from very blunt tips with curvature radii up to 3 μm. The values of the effective work function calculated from Fowler–Nordheim plot were in the range from 0.3 to 1.2 eV. Two models for an explanation of the experimental data are proposed.
Characterization of thin copper films grown via chemical vapor deposition using liquid coinjection of trimethylvinylsilane and (hexafluoroacetylacetonate) Cu (trimethylvinylsilane)
Authors: Parmeter J. E. , Petersen G. A. , Smith P. M. , Apblett C. A. , Reid J. S. , Norman J. A. T. , Hochberg A. K. , Roberts D. A. , Omstead Thomas R.
Published: July 2002

We have developed a technique recently for copper chemical vapor deposition utilizing direct liquid coinjection of trimethylvinylsilane (TMVS) and the copper (I) precursor (hexafluoroacetylacetonate) Cu (TMVS). We present here an investigation of the properties of copper films deposited using this technique. The films were grown on Si3N4 substrates at temperatures in the range of 220–250 °C and characterized using several experimental techniques, with an emphasis placed on factors influencing copper film resistivity. The average as-deposited film resistivity is 1.86 μΩ cm; this value is reduced to 1.82 μΩ cm when the effects of surface scattering are taken into account. The resistivity is essentially independent of film thickness for thicknesses between 0.2 and 3.5 μm, and is reduced by less than 0.05 μΩ cm by annealing at 400–600 °C in vacuum. The total impurity content of the films is approximately 100 parts per million. The film density is 97±2% of the bulk copper value. The average grain size increases with film thickness and falls in the range of 0.5–1.5 μm. Morphological defects are the main cause of the resistivities (after adjusting for surface scattering) being approximately 0.14 μΩ cm above the bulk copper value (1.68 μΩ cm). Comparison of thickness and resistivity measurements for rough as-deposited films and smooth chemical-mechanical polished films shows that the surface roughness causes surface profilometry to overestimate the thicknesses of the unpolished films by approximately 1300 Å. This effect can lead to both artificially high resistivity values and a false dependence of resistivity on film thickness if profilometry measurements for the unpolished films are not properly corrected.
Development of highly conductive cantilevers for atomic force microscopy point contact measurements
Authors: Thomson R. E. , Moreland John
Published: July 2002

Several techniques for improving the electrical conductivity of micromachined silicon cantilevers for atomic force microscopy point contact measurements were investigated. The techniques studied included sputtering or evaporating thin layers of gold, platinum or silver onto the lower surface of the cantilever to create a conducting metal layer, and doping the cantilevers with phosphorus. It was found that the lowest resistance contacts to a gold surface can be made by the metal coated tips, which can make stable point contacts with resistances as low as 30 Ω at a tip sample force of 15 μN.
Local modification of elastic properties of polystyrene–polyethyleneoxide blend surfaces
Authors: Nie H.-Y. , Motomatsu M. , Mizutani W. , Tokumoto H.
Published: July 2002

Modifications of the phase-separated surface of polystyrene–polyethyleneoxide (PS-PEO) blend films were carried out by using an atomic force microscope. On PEO, contrary to PS, a scanning of a tip with large forces of 50 nN resulted in a modification of surface and increased the elastic stiffness. The modification was seen as regular stripes perpendicular to the scanning direction, which may be caused by the rearrangement of the PEO folding structure as a result of a balance of various forces during scanning. This rearrangement may increase the density of the films and hence causes the increase of the elastic stiffness. On the stripes, molecular images were obtained with friction force microscope, reflecting the folding structure of PEO.
Atomic structure of the diamond (100) surface studied using scanning tunneling microscopy
Authors: Stallcup II R. E. , Villarreal L. M. , Lim S. C. , Akwani I. , Aviles A. F. , Perez J. M.
Published: July 2002

Atomic resolution ultrahigh-vacuum scanning tunneling microscopy studies of chemical-vapor-deposition-grown epitaxial diamond (100) films are reported. After growth, the surface of the epitaxial films is amorphous at the atomic scale. After 2 min of exposure to atomic hydrogen at 30 Torr, the surface is observed to consist of amorphous regions and (2×1) dimer reconstructed regions. After 5 min of exposure to atomic hydrogen, the surface is observed to consist mostly of (2×1) dimer reconstructed regions. These observations are compared with a recent model for chemical-vapor-deposition diamond growth. Tunneling current versus voltage spectroscopy of undoped and boron-doped epitaxial diamond (100) films is also reported.
Generation of diffraction-free beams for applications in optical microlithography
Authors: Erdélyi M. , Horváth Z. L. , Szabó G. , Bor Zs. , Tittel F. K. , Cavallaro J. R. , Smayling M. C.
Published: July 2002

A new concept based on a Fabry–Pérot interferometer for the generation of nondiffracting Bessel beams is described and proposed for potential applications in microlithography such as the fabrication of small isolated patterns. It was experimentally demonstrated that the depth of focus can be increased by a factor of about 2, and simultaneously the transverse resolution improved by a factor of 1.6, when using this technique to image contact holes. The properties of simultaneous imaging of two contact holes were also investigated. It was shown experimentally that, even in the most critical case (when the first diffraction rings overlap), undesirable interference effects between the adjacent contact holes can be eliminated by means of a phase shifting technique.
Photon-induced localization and final-state correlation effects in optically absorbing materials
Authors: Aspnes D. E. , Mantese L. , Bell K. A. , Rossow U.
Published: July 2002

Two consequences of the absorption of light in optically absorbing materials that appear not to have been recognized previously are: (1) localization of the final electron and hole states involved in the absorption process into wave packets and (2) propagation of these wave packets with their respective group velocities. We demonstrate the existence of these phenomena by applying first-order time-dependent perturbation theory to a simple model that can be solved analytically even when correlations that are ordinarily discarded in the random phase approximation are retained. This approach provides a natural explanation of components in surface- and interface-optical spectra that are related to energy derivatives of the bulk dielectric function εb and apparent differences in nominally bulk critical point energies Eg and broadening parameters Γ depending on surface conditions.
Investigation of citric acid-hydrogen peroxide etched GaAs and Al0.3Ga0.7As surfaces by spectroscopic ellipsometry
Authors: Snyder P. G. , Cho S.-J.
Published: July 2002

GaAs (100) surfaces were etched in citric acid-hydrogen peroxide (C6H8O7:H2O2) solutions with volume ratios ranging from 1:1 to 10:1. Ex situ variable angle spectroscopic ellipsometry measurements (1.5–5.5 eV) were made before and after etching for periods of up to 8 min. Analysis of these data indicated that low volume ratios (⩽2:1), with corresponding low etch rates, produced a thin interfacial layer (which might represent microscopic roughness) beneath a porous oxide. For a 1:1 ratio the interfacial layer thickness increased with etch time, while for a 2:1 ratio it stabilized at a small value (≅2 nm). Higher volume ratios (⩾3:1), associated with much higher etch rates, produced qualitatively different overlayers which were more absorbing and 4–6 nm thick. Their optical constants could be modeled as a mixture of a small fraction (typically 5%–10%) of crystalline arsenic in a low-dielectric medium, using an effective medium approximation. Similar effects were seen in etched Al0.3Ga0.7As surfaces. Low etch rates (volume ratio of 5:1 or less) resulted in nearly normal oxide overlayers. A high etch rate (volume ratio 10:1) resulted in an absorbing layer similar to the one seen on rapidly etched GaAs surfaces, 8–12 nm thick.
Observation of the trajectories of particles in process equipment by an in situ monitoring system using a laser light scattering method
Authors: Ito Natsuko , Moriya Tsuyoshi , Uesugi Fumihiko , Doi Hiroshi , Sakamoto Shingo , Hayashi Yuji
Published: July 2002

An in situ scattered laser light measurement system, which can detect individual particles and observe their trajectories, has been produced experimentally and has been used with tungsten (W) etchback reactive ion etching (RIE) equipment. The particles which are smaller than 100 nm in size can be detected during plasma emission if the stray light that is caused by the laser light is properly suppressed. The trajectories of the particles are successfully observed in the W etchback RIE chamber by using this system under mass production conditions. Not only the appearance of the particle but also the direction of particle trajectory correlate distinctly with the specific operating state of the equipment. When the rf power was turned off, many of the particles that were observed seemed to be drawn towards the wafer. On the other hand, during injection of the N2 purge gas to the process chamber, the few particles that were frequently observed seemed to fall down, away from the wafer.
Refractive index measurements of ZnSe-based ternary epitaxial layers grown by molecular-beam epitaxy on GaAs (100)
Authors: Peiris F. C. , Lee S. , Bindley U. , Furdyna J. K.
Published: July 2002

ZnSe-based II–VI ternary alloys, such as ZnBeSe, ZnMgSe, and ZnCdSe, have been shown to be excellent candidates for light-emitting device applications in the short-wavelength visible range. Since design of optical semiconductor devices requires knowledge of refractive indices of all materials involved, we studied refractive indices of Zn1−xBexSe, Zn1−xMgxSe, and Zn1−xCdxSe epitaxial layers. The samples were grown by molecular-beam epitaxy in mole fractions ranges between 0⩽x⩽0.81, 0⩽x⩽0.59, and 0⩽x⩽0.57 for Zn1−xBexSe, Zn1−xMgxSe, and Zn1−xCdxSe, respectively. The alloy concentration x was determined by x-ray diffraction. All samples exhibited very high crystalline quality, even at relatively high values of x. A prism-to-film coupler technique, which involves optical tunneling via evanescent fields, was employed to accurately determine the indices of refraction. The variation of the refractive index with alloy composition at room temperature was determined at the wavelength of 632.8 nm.
Maskless micro-ion-beam reduction lithography
Authors: Ngo V. V. , Barletta W. , Gough R. , Lee Y. , Leung K. N. , Zahir N. , Patterson D.
Published: July 2002

An ion projection lithography (IPL) technique called maskless micro-ion-beam reduction lithography (MMRL) is being studied for future dynamic random access memory and microprocessors manufacturing. In addition to minimum feature sizes of 50 nm or less required of next generation lithography, this MMRL system is proposed to completely eliminate the first stage of the conventional IPL system that contains the complicated beam optics design in front of the stencil mask and the mask itself. Its main components consist of a multi-cusp, rf plasma generator, a multi-beamlet extraction system, and an accelerator column for beam reduction. The viability of this MMRL system hinges upon the successful development of these components, most importantly the proposed all-electrostatic accelerator column. This article describes the different components of the MMRL system and its ion optics. Computational results of beam demagnification and optics optimization are also presented along with design progress of the prototype MMRL system.
Proximity effect correction by the GHOST method using a scattering stencil mask
Authors: Yamashita Hiroshi , Nomura Eiichi , Manako Shoko , Kobinata Hideo , Nakajima Ken , Nozue Hiroshi
Published: July 2002

Proximity effect correction (PEC) by the SCALPEL GHOST method, using a scattering stencil mask in which mask-scattered electrons are used as a correction beam, is discussed and a new correction dose adjustment method is proposed. We simulate electron scattering in order to trace electron trajectories in the Si membrane and obtain exiting angular distribution by using a Monte Carlo method. We found that the GHOST can be used for a PEC using a Si scattering stencil mask of about 0.3–2 μm thickness under a 100 kV accelerating voltage. In the SCALPEL technique, the correction dose is adjusted by changing the radius of the annular aperture size for different mask conditions and for various under-layer conditions. In the method proposed, the vertical position of an additional correction dose adjustment aperture is shifted. The angular range becomes narrow as the aperture shifts so that the electron transmission determining the correction dose can be corrected in the doublet optics. This method can also be applied to the membrane mask.
Megahertz silicon atomic force microscopy (AFM) cantilever and high-speed readout in AFM-based recording
Authors: Hosaka S. , Etoh K. , Kikukawa A. , Koyanagi H.
Published: July 2002

Small atomic force microscopy (AFM) cantilever with a maximum resonant frequency of about 6.6 MHz was developed using a Si microprocess with silicon-on-insulator wafer. The cantilever was triangular in shape with a length of 7–20 μm and a thickness of <0.3 μm and had a tip on the lever. These structures were precisely fabricated by buffer step and prestep and using dual-side aligner. Furthermore, we developed a new optical lever deflection detection system for the small cantilever with a magnifying power of 0.2 μm/Å and a spot size of 2 μm. We demonstrate a high resonant frequency of the cantilever and a high speed readout at higher than 5 Mb/s using the prototype of rotation AFM recording system with a new detection system.
Effects of conduction type on field-electron emission from single Si emitter tips with extraction gate
Authors: Matsukawa T. , Kanemaru S. , Tokunaga K. , Itoh J.
Published: July 2002

Field emission characteristics from n- and p-type silicon gated emitter tips have been investigated in detail by means of experiments and theoretical estimation of band bending induced by surface states. Single-tip emitters have been fabricated from n- and p-type silicon and their current–voltage characteristics have been evaluated. The field emission from the p-type emitter has been found to occur at a lower extraction voltage than that of the n-type emitter. As the theoretical approach to the origin of the phenomena, potential distribution in the emitter tips has been calculated by using a device simulation technique. The surface states of the n-type emitter tip are negatively charged and form a potential barrier against the electrons. On the contrary, there is no potential barrier in the p-type tips. The potential barrier in the n-type tip prevents electrons from reaching the tip apex. This is the reason why the emission current of the n-type emitter was suppressed lower than that of the p-type emitter.
Plasma-assisted molecular beam epitaxy for ZnO based II–VI semiconductor oxides and their heterostructures
Authors: Chen Yefan , Ko Hang-ju , Hong Soon-ku , Sekiuchi Takashi , Yao Takafumi , Segawa Yusaburo
Published: July 2002

Plasma-assisted molecular beam epitaxy of ZnO epilayers and MgZnO/ZnO heterostructures on Al2O3(0001) substrates is described. A thin MgO layer is employed as a buffer for ZnO. The influence of the buffer on the initial growth of ZnO is discussed with the corresponding reflection high-energy electron diffraction (RHEED) studies. We found that the MgO buffer promotes the lateral growth of ZnO, which results in two-dimensional growth. A 3×3 reconstruction is observed and the RHEED intensity oscillations are recorded. The RHEED oscillations have been used in situ to monitor and control the growth of MgZnO/ZnO heterostructures. MgZnO/ZnO single-quantum-well structures have been grown and studied by cathodoluminescence.
Near-Field Coherent Spectroscopy and Microscopy of a Quantum Dot System
Authors: Guest J. R. , Stievater T. H. , Chen Gang , Tabak E. A. , Orr B. G. , Steel D. G. , Gammon D. , Katzer D. S.
Published: July 2002

We combined coherent nonlinear optical spectroscopy with nano–electron volt energy resolution and low-temperature near-field microscopy with subwavelength resolution (<λ/2) to provide direct and local access to the excitonic dipole in a semiconductor nanostructure quantum system. Our technique allows the ability to address, excite, and probe single eigenstates of solid-state quantum systems with spectral and spatial selectivity while simultaneously providing a measurement of all the various time scales of the excitation including state relaxation and decoherence rates. In analogy to scanning tunneling microscopy measurements, we can now map the optical local density of states of a disordered nanostructure. These measurements lay the groundwork for studying and exploiting spatial and temporal coherence in the nanoscopic regime of solid-state systems.
How Molecules Make Organisms Work
Authors: Willmer Pat
Published: July 2002

Biochemical Adaptation
Mechanism and Process in Physiological Evolution. Peter W. Hochachka and George N. Somero. Oxford University Press, New York, 2002. 478 pp. $80, £62.50. ISBN 0-19-511702-6. Paper, $40, £29.50. ISBN 0-19-511703-4.

Hochachka and Somero examine how widespread biochemical systems have been modified to function throughout the broad range of environmental conditions that Earth's biota experiences, and they discuss the processes involved in the development of novel physiological functions.
Dissociation of Methane into Hydrocarbons at Extreme (Planetary) Pressure and Temperature
Authors: Ancilotto F. , Chiarotti G. L. , Scandolo S. , Tosatti E.
Published: July 2002

Constant-pressure, first-principles molecular dynamic simulations were used to investigate the behavior of methane at high pressure and temperature. Contrary to the current interpretation of shock-wave experiments, the simulations suggest that, below 100 gigapascals, methane dissociates into a mixture of hydrocarbons, and it separates into hydrogen and carbon only above 300 gigapascals. The simulation conditions (100 to 300 gigapascals; 4000 to 5000 kelvin) were chosen to follow the isentrope in the middle ice layers of Neptune and Uranus. Implications on the physics of these planets are discussed.
Effect of Transmembrane and Cytoplasmic Domains of IgE on the IgE Response
Authors: Achatz Gernot , Nitschke Lars , Lamers Marinus C.
Published: July 2002

B cells use immunoglobulin M (IgM) and IgD as antigen receptors, but after contact with antigen they can switch and use IgG, IgA, or IgE. In mice lacking the transmembrane and cytoplasmic domains of IgE, serum IgE is reduced by more than 95 percent and, after immunization, specific responses are negligible. In mice lacking most of the cytoplasmic tail of IgE, serum IgE levels are reduced by 50 percent and specific responses are reduced by 40 to 80 percent, without a clear secondary response. Thus, membrane expression is indispensable for IgE secretion in vivo, and the cytoplasmic tail influences the degree and quality of the response.
Defective TNF-α-Induced Apoptosis in STAT1-Null Cells Due to Low Constitutive Levels of Caspases
Authors: Kumar Aseem , Commane Mairead , Flickinger Thomas W. , Horvath Curt M. , Stark George R.
Published: July 2002

Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells are resistant to apoptosis by tumor necrosis factor α (TNF-α). Reintroduction of STAT1α restored both TNF-α–induced apoptosis and the expression of Ice, Cpp32, and Ich-1. Variant STAT1 proteins carrying point mutations that inactivate domains required for STAT dimer formation nevertheless restored protease expression and sensitivity to apoptosis, indicating that the functions of STAT1 required for these activities are different from those that mediate induced gene expression.
"New View" of Protein Folding Reconciled with the Old Through Multiple Unfolding Simulations
Authors: Lazaridis Themis , Karplus Martin
Published: July 2002

Twenty-four molecular dynamics trajectories of chymotrypsin inhibitor 2 provide a direct demonstration of the diversity of unfolding pathways. Comparison with experiments suggests that the transition state region for folding and unfolding occurs early with only 25 percent of the native contacts and that the root-mean-square deviations between contributing structures can be as large as 15 angstroms. Nevertheless, a statistically preferred unfolding pathway emerges from the simulations; disruption of tertiary interactions between the helix and a two-stranded portion of the β sheet is the primary unfolding event. The results suggest a synthesis of the “new” and the classical view of protein folding with a preferred pathway on a funnel-like average energy surface.
Isolation of a Benzene Valence Isomer with One-Electron Phosphorus-Phosphorus Bonds
Authors: Canac Yves , Bourissou Didier , Baceiredo Antoine , Gornitzka Heinz , Schoeller Wolfgang W. , Bertrand Guy
Published: July 2002

A tetraphosphabenzene analog of the postulated
anti
-tricyclohexylene, a singlet biradical valence isomer of benzene, has been isolated. The tricyclic derivative features one-electron phosphorus-phosphorus bonds, which result from the π*-π* interaction between two diphosphirenyl radicals. Such one-electron bonds may play a wider role in phosphorus chemistry.
Fast Recession of a West Antarctic Glacier
Authors: Rignot E. J.
Published: July 2002

Satellite radar interferometry observations of Pine Island Glacier, West Antarctica, reveal that the glacier hinge-line position retreated 1.2 ± 0.3 kilometers per year between 1992 and 1996, which in turn implies that the ice thinned by 3.5 ± 0.9 meters per year. The fast recession of Pine Island Glacier, predicted to be a possible trigger for the disintegration of the West Antarctic Ice Sheet, is attributed to enhanced basal melting of the glacier floating tongue by warm ocean waters.
Polarimetric Constraints on the Optical Afterglow Emission from GRB 990123
Authors: Hjorth Jens , Björnsson Gunnlaugur , Andersen Michael I. , Caon Nicola , Cairós Luz Marina , Castro-Tirado Alberto J. , Osorio Marı́a Rosa Zapatero , Pedersen Holger , Costa Enrico
Published: July 2002

Polarization of the optical emission from GRB 990123 was measured on 24.17 January 1999 universal time with the Nordic Optical Telescope. An upper limit of 2.3% on the linear polarization was found. Accurate polarization measurements provide important clues to the blast wave geometry and magnetic field structure of gamma-ray bursts (GRBs). The lack of detectable polarization for GRB 990123 indicates that the optical afterglow was produced by a blast wave of unknown geometry with an insignificant coherent magnetic field or by a beamed outflow at high Lorentz factor seen at a small viewing angle. Such a collimated jet would help solve the problem of energy release in this exceptionally luminous cosmological burst.
Remote Triggering of Waves in an Electrochemical System
Authors: Christoph J. , Strasser P. , Eiswirth M. , Ertl G.
Published: July 2002

In the potentiostatic electrochemical oxidation of formic acid on a platinum ring electrode under bistable conditions, an appropriate perturbation at one location of the ring can cause the emergence of a wave on the opposite side (remote triggering). These findings can be rationalized in terms of the nonlocal coupling function of the system and are theoretically reproduced by solution of the corresponding reaction-migration equation.
Selection-Based Biodiversity at a Small Spatial Scale in a Low-Dispersing Insular Bird
Authors: Blondel Jacques , Dias Paula C. , Perret Philippe , Maistre Marie , Lambrechts Marcel M.
Published: July 2002

The blue tit is a highly mobile small passerine found in deciduous and evergreen oaks. In mainland populations, gene flow results in local maladaptive timing of breeding in evergreen oak forests, the rarer habitat. However, on the island of Corsica, two populations only 25 kilometers apart are highly specialized and differ between the two habitat types in breeding and morphological traits. In contrast to theoretical predictions about the homogenizing effects of gene flow, this highlights evolutionary consequences of habitat diversification and isolation at a small spatial scale in insular organisms, which should be taken into account in conservation policies.
The Protein Kinase p90 Rsk as an Essential Mediator of Cytostatic Factor Activity
Authors: Bhatt Ramesh R. , Ferrell James E.
Published: July 2002

Persistent activation of p42 mitogen-activated protein kinase (p42 MAPK) during mitosis induces a “cytostatic factor” arrest, the arrest responsible for preventing the parthenogenetic activation of unfertilized eggs. The protein kinase p90 Rsk is a substrate of p42 MAPK; thus, the role of p90 Rsk in p42 MAPK-induced mitotic arrest was examined.
Xenopus laevis
egg extracts immunodepleted of Rsk lost their capacity to undergo mitotic arrest in response to activation of the Mos–MEK-1–p42 MAPK cascade of protein kinases. Replenishing Rsk-depleted extracts with catalytically competent Rsk protein restored the ability of the extracts to undergo mitotic arrest. Rsk appears to be essential for cytostatic factor arrest.
Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant
Helicobacter pylori
Infections in Mice
Authors: Jenks Peter J. , Ferrero Richard L. , Tankovic Jacques , Thiberge Jean-Michel , Labigne Agnès
Published: July 2002

The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the
rdxA
gene of
Helicobacter pylori
was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant
H. pylori
infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic
rdxA
mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive
H. pylori
SS1 strain or a metronidazole-resistant
rdxA
SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for
H. pylori
. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective
rdxA
mutants or between those of matched metronidazole-sensitive and -resistant
H. pylori
isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the
rdxA
mutant (
P
≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (
P
≤ 0.001) and cleared infection from one of seven mice inoculated with the
rdxA
mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against
H. pylori
and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant
H. pylori
infections from mice.
In Vitro Activities of Ravuconazole (BMS-207147) against 541 Clinical Isolates of
Cryptococcus neoformans
Authors: Yamazumi T. , Pfaller M. A. , Messer S. A. , Houston A. , Hollis R. J. , Jones R. N.
Published: July 2002

The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of
Cryptococcus neoformans
. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (MIC at which 90% of the isolates are inhibited [MIC
90
], 0.25 μg/ml) was more active than either itraconazole (MIC
90
, 0.5 μg/ml) or fluconazole (MIC
90
, 8 μg/ml). Among the isolates inhibited by ≥16 μg of fluconazole/ml, 90.2% were inhibited by ≤1 μg of ravuconazole/ml. On the basis of our findings and the favorable pharmacokinetic properties of ravuconazole, we suggest that ravuconazole may be useful for the treatment of infectious diseases due to
C. neoformans
and that further clinical studies to confirm these promising in vitro results are warranted.
Reversion of the Glycopeptide Resistance Phenotype in
Staphylococcus aureus
Clinical Isolates
Authors: Boyle-Vavra Susan , Berke Sarah K. , Lee Jean C. , Daum Robert S.
Published: July 2002

The recent identification of glycopeptide intermediate-resistant
Staphylococcus aureus
(GISA) clinical isolates has provided an opportunity to assess the stability of the glycopeptide resistance phenotype by nonselective serial passage and to evaluate reversion-associated cell surface changes. Three GISA isolates from the United States (MIC of vancomycin = 8 μg/ml) and two from Japan (MICs of vancomycin = 8 and 2 μg/ml) were passaged daily on nutrient agar with or without vancomycin supplementation. After 15 days of passage on nonselective medium, vancomycin- and teicoplanin-susceptible revertants were obtained from each GISA isolate as determined by broth dilution MIC. Revertant isolates were compared with parent isolates for changes in vancomycin heteroresistance, capsule production, hemolysis phenotype, coagulase activity, and lysostaphin susceptibility. Several revertants lost the subpopulations with intermediate vancomycin resistance, whereas two revertants maintained them. Furthermore, although all of the parent GISA isolates produced capsule type 5 (CP5), all but one revertant tested no longer produced CP5. In contrast, passage on medium containing vancomycin yielded isolates that were still intermediately resistant to vancomycin, had no decrease in the MIC of teicoplanin, and produced detectable CP5. No consistent changes in the revertants in hemolysis phenotype, lysostaphin susceptibility, or coagulase activities were discerned. These data indicate that the vancomycin resistance phenotype is unstable in clinical GISA isolates. Reversion of the vancomycin resistance phenotype might explain the difficulty in isolating vancomycin-resistant clinical isolates from the blood of patients who fail vancomycin therapy and, possibly, may account for some of the difficulties in identifying GISA isolates in the clinical laboratory.
Comparative In Vitro Activities of Ciprofloxacin, Gemifloxacin, Grepafloxacin, Moxifloxacin, Ofloxacin, Sparfloxacin, Trovafloxacin, and Other Antimicrobial Agents against Bloodstream Isolates of Gram-Positive Cocci
Authors: Hardy Dwight , Amsterdam Daniel , Mandell Lionel A. , Rotstein Coleman
Published: July 2002

The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistant
Staphylococcus epidermidis
isolates, and coagulase-negative staphylococci.
Compartmental Pharmacokinetics and Tissue Distribution of Multilamellar Liposomal Nystatin in Rabbits
Authors: Groll Andreas H. , Mickiene Diana , Werner Kathy , Petraitiene Ruta , Petraitis Vidmantas , Calendario Myrna , Field-Ridley Aida , Crisp Jeremy , Piscitelli Stephen C. , Walsh Thomas J.
Published: July 2002

The plasma pharmacokinetics of multilamellar liposomal nystatin were studied in normal, catheterized rabbits after single and multiple daily intravenous administration of dosages of 2, 4, and 6 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of liposomal nystatin were measured as those of nystatin by a validated high-performance liquid chromatography method, and plasma concentration data were fitted into a two-compartment open model. Across the investigated dosage range, liposomal nystatin demonstrated nonlinear kinetics with more than proportional increases in the AUC
0–24
and decreasing clearance, consistent with dose-dependent tissue distribution and/or a dose-dependent elimination process. After single-dose administration, the mean
C
max
increased from 13.07 μg/ml at 2 mg/kg to 41.91 μg/ml at 6 mg/kg (
P
< 0.001); the AUC
0–24
changed from 11.65 to 67.44 μg · h/ml (
P
< 0.001), the

V
d

changed from 0.205 to 0.184 liters/kg (not significant), the CL

t

from 0.173 to 0.101 liters/kg · h (
P
< 0.05), and terminal half-life from 0.96 to 1.51 h (
P
< 0.05). There were no significant changes in pharmacokinetic parameters after multiple dosing over 14 days. Assessment of tissue concentrations of nystatin near peak plasma levels after multiple dosing over 15 days revealed preferential distribution to the lungs, liver, and spleen at that time point. Substantial levels were also found in the urine, raising the possibility that renal excretion may play a significant role in drug elimination. Liposomal nystatin administered to rabbits was well tolerated and displayed nonlinear pharmacokinetics, potentially therapeutic peak plasma concentrations, and substantial penetration into tissues. Pharmacokinetic parameters were very similar to those observed in patients, thus validating results derived from infection models in the rabbit and allowing inferences to be made about the treatment of invasive fungal infections in humans.
Inhibition of Human Rhinovirus-Induced Cytokine Production by AG7088, a Human Rhinovirus 3C Protease Inhibitor
Authors: Zalman L. S. , Brothers M. A. , Dragovich P. S. , Zhou R. , Prins T. J. , Worland S. T. , Patick A. K.
Published: July 2002

Symptom severity in patients with human rhinovirus (HRV)-induced respiratory illness is associated with elevated levels of the inflammatory cytokines interleukin-6 (IL-6) and IL-8. AG7088 is a novel, irreversible inhibitor of the HRV 3C protease. In this study, AG7088 was tested for its antiviral activity and ability to inhibit the production of IL-6 and IL-8 in a human bronchial epithelial cell line, BEAS-2B. Infection of BEAS-2B cells with HRV 14 resulted in the production of both infectious virus and the cytokines IL-6 and IL-8. Treatment of HRV 14-infected cells with AG7088 resulted in a statistically significant (P, <0.05) dose-dependent reduction in the levels of infectious virus as well as IL-6 and IL-8 released into the cell supernatant compared to the results obtained for compound-free infected cells. AG7088 was also able to inhibit the replication of HRV 2 and 16 in BEAS-2B cells. In time-of-addition studies, AG7088 could be added as late as 14 to 26 h after HRV 14 infection of BEAS-2B cells and still result in a statistically significant (P, <0.05) reduction in the levels of infectious virus, IL-6, and IL-8 compared to the results obtained for compound-free infected cells. These findings have implications for the development of an antirhinovirus agent that may not only block virus replication but also diminish symptoms.
Glycopeptide-Resistant
Enterococcus faecium
BM4416 Is a VanD-Type Strain with an Impaired
d
-Alanine:
d
-Alanine Ligase
Authors: Perichon Bruno , Casadewall Barbara , Reynolds Peter , Courvalin Patrice
Published: July 2002

VanD-type
Enterococcus faecium
BM4416 was constitutively resistant to vancomycin and to teicoplanin by synthesis of peptidoglycan precursors ending in
d
-alanyl–
d
-lactate. Like
E. faecium
BM4339, the only VanD-type strain described so far, BM4416 produced an impaired
d
-alanine:
d
-alanine ligase. Unlike for BM4339, which had a 5-bp insertion in
ddl
, inactivation of the gene in BM4416 was due to insertion of IS
19
.
Does Long-Term Itraconazole Prophylaxis Result in In Vitro Azole Resistance in Mucosal
Candida albicans
Isolates from Persons with Advanced Human Immunodeficiency Virus Infection?
Authors: Goldman Mitchell , Cloud Gretchen A. , Smedema Melinda , LeMonte Ann , Connolly Patricia , McKinsey David S. , Kauffman Carol A. , Moskovitz Bruce , Wheat L. Joseph ,   The National Institute of Allergy and Infectious Diseases Mycoses Study Group
Published: July 2002

The effects of prolonged itraconazole exposure on the susceptibility of
Candida albicans
isolates to itraconazole and fluconazole have not been well characterized. A recent placebo-controlled study of long-term itraconazole antifungal prophylaxis in persons with advanced human immunodeficiency virus infection afforded the opportunity to address this question. Mucosal
Candida
sp. isolates were obtained from subjects who developed oropharyngeal or esophageal candidiasis, and in vitro susceptibilities of the last isolate obtained at removal from the study as a prophylaxis failure were compared in itraconazole and placebo recipients. More subjects in the placebo group (74 of 146 [51%]) than in the itraconazole group (51 of 149 [34%]) developed mucosal candidiasis (
P
= 0.004). A total of 112 isolates were recovered from 56 of the 74 (76%) subjects with mucosal candidiasis assigned to the placebo group, compared to 97 isolates from 45 of the 51 (88%) subjects in the itraconazole group.
C. albicans
accounted for 98% of isolates in the placebo group and 89% of isolates in the itraconazole group. The itraconazole MIC at which 50% of the isolates tested were inhibited (MIC
50
) for last-episode isolates from the itraconazole group was 0.125 μg/ml compared to 0.015 μg/ml for the placebo group subjects,
P
= 0.0001. The MIC
50
of fluconazole for the last isolates from the itraconazole group was 1.5 μg/ml compared to 0.5 μg/ml for the placebo subjects (
P
= 0.005). A lower proportion of isolates recovered from subjects on itraconazole therapy were classified as susceptible to itraconazole (63%) compared to isolates from the placebo group (96%) (
P
= 0.001). Similarly, a lower proportion of
C. albicans
isolates from subjects on itraconazole therapy were susceptible to fluconazole (78%) compared to isolates from the placebo group (96%) (
P
= 0.01). Also, the proportion of isolates that were not fully susceptible to itraconazole or fluconazole was greater in patients assigned to the itraconazole group than the placebo group (itraconazole susceptibility, 37 and 4%, respectively (
P
= 0.001); fluconazole susceptibility, 23 and 4%, respectively (
P
= 0.01). In conclusion, long-term itraconazole prophylaxis in patients with AIDS is associated with reduction in susceptibility to itraconazole and cross-resistance to fluconazole.
Indinavir Population Pharmacokinetics in Plasma and Cerebrospinal Fluid
Authors: Letendre Scott L. , Capparelli Edmund V. , Ellis Ronald J. , McCutchan J. Allen ,   The HIV NEUROBEHAVIORAL RESEARCH CENTER GROUP
Published: July 2002

Plasma and cerebrospinal fluid (CSF) indinavir concentrations were measured by high-performance liquid chromatography. The median concentration in plasma exceeded that in CSF 10-fold. The modeled CSF curve was flat at 155 nM, and the estimated ratio of the areas under the CSF and plasma concentration-time curves was 6%. We conclude that CSF indinavir concentrations are lower than levels in plasma but exceed the clinical 95% inhibitory concentration range.
Antibiotic Activity and Characterization of BB-3497, a Novel Peptide Deformylase Inhibitor
Authors: Clements John M. , Beckett R. Paul , Brown Anthony , Catlin Graham , Lobell Mario , Palan Shilpa , Thomas Wayne , Whittaker Mark , Wood Stephen , Salama Sameeh , Baker Patrick J. , Rodgers H. Fiona , Barynin Vladimir , Rice David W. , Hunter Michael G.
Published: July 2002

Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the
N
-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy. To identify novel PDF inhibitors, we screened a metalloenzyme inhibitor library and identified an
N
-formyl-hydroxylamine derivative, BB-3497, and a related natural hydroxamic acid antibiotic, actinonin, as potent and selective inhibitors of PDF. To elucidate the interactions that contribute to the binding affinity of these inhibitors, we determined the crystal structures of BB-3497 and actinonin bound to
Escherichia coli
PDF at resolutions of 2.1 and 1.75 Å, respectively. In both complexes, the active-site metal atom was pentacoordinated by the side chains of Cys 90, His 132, and His 136 and the two oxygen atoms of
N
-formyl-hydroxylamine or hydroxamate. BB-3497 had activity against gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant
Enterococcus faecalis
, and activity against some gram-negative bacteria. Time-kill analysis showed that the mode of action of BB-3497 was primarily bacteriostatic. The mechanism of resistance was via mutations within the formyltransferase gene, as previously described for actinonin. While actinonin and its derivatives have not been used clinically because of their poor pharmacokinetic properties, BB-3497 was shown to be orally bioavailable. A single oral dose of BB-3497 given 1 h after intraperitoneal injection of
S. aureus
Smith or methicillin-resistant
S. aureus
protected mice from infection with median effective doses of 8 and 14 mg/kg of body weight, respectively. These data validate PDF as a novel target for the design of a new generation of antibacterial agents.