bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron-beam/ultraviolet hybrid exposure combined with novel bilayer resist system for a 0.15 μm T-shaped gate fabrication process
Authors: Takano H. , Nakano H. , Minami H. , Hosogi K. , Yoshida N. , Sato K. , Hirose Y. , Tsubouchi N.
Published: July 2002

Electron-beam/ultraviolet (UV) exposure technology to produce undercut T-shaped resist cavities with bottom openings as small as 0.15 μm is demonstrated with a novel bilayer resist system for AlInAs/InGaAs high electron mobility transistors operated at the millimeter-wave band. We employed an image reversal resist (AZ5206E) for the top layer and a polydimethyl glutarimide (PMGI) for the bottom layer. The top layer is delineated by UV exposure and the bottom layer is delineated by electron-beam direct writing. These resist layers are developed layer by layer in different content aqueous tetramethyl ammonium hydroxide solution. Resist profiles are extremely well controlled because exposure and development of both layers are completely independent. A reliable overhang structure for metal liftoff, with a 0.15 μm footprint, was obtained. Gate length variation of less than ±10% on a 3-in.-diam InP substrate was successfully accomplished. In addition, an interesting phenomenon was noted. The combination of these two resists leads to an electron-beam sensitivity decrease of PMGI. This phenomenon is closely related to the change of molecular weight distribution in PMGI. The novel bilayer resist system also allows the further improvement of resolution. This would provide a practical means for electron-beam lithography in the nanometer region.
Low resistivity Al–RE (RE=La, Pr, and Nd) alloy thin films with high thermal stability for thin-film-transistor interconnects
Authors: Takayama Shinji , Tsutsui Naganori
Published: July 2002

The addition of light rare-earth (RE) metal elements (La, Pr, and Nd) to Al thin films with about 2–7 at. % markedly decreases the grain size of the Al matrix more than 50% compared with those of pure Al. Such addition largely suppresses growth of thermal defects of hillocks and whiskers at high temperatures (350–450 °C). A large number of fine metallic compounds of Al11RE3 and/or Al3RE (RE=La, Pr, and Nd) were segregated in an Al matrix, mostly at grain boundaries, after annealing at 350 °C. The resistivities of the films after annealing at the above temperatures show low values of less than 6 μΩ cm compared with those of current thin-film-transistor liquid-crystal displays gate electrode materials (more than about 15 μΩ cm), without the salient formation of hillocks or whiskers on the surfaces.
Replication of near 0.1 μm hole patterns by using x-ray lithography
Authors: Kikuchi Yukiko , Kihara Naoko , Sugihara Shinji , Saitoh Satoshi , Kondo Kenzo , Nomura Hiroshi , Ozaki Tohru
Published: July 2002

The feasibility of x-ray lithography in applying device process was studied through fabrication of a small circuit consisting of experimental stacked film and contact holes numbering about 1k with replicated sizes from 0.6 to 0.085 μm. To resolve fine contact holes, in-house chemically amplified positive resist was used by employing a high contrast post-exposure-bake condition. By measuring the resistance and yields of prepared circuits, we have evaluated the reliability of the circuits. High yield of larger than 0.9 was obtained for contact holes larger than 0.15 μm, and prepared circuits were found to be feasible down to 0.085 μm.
Trench isolation at 300 nm active pitch using x-ray lithography
Authors: Perera Asanga H. , Thompson M. , Hector S. , Iyer S. , Azrak M. J. , Zavala M.
Published: July 2002

A nanofabrication technology providing device isolation at an active pitch of 300 nm has been developed using x-ray lithography for pattern definition. The isolation scheme uses oxide filled trenches etched into the silicon substrate, which are 300–350 nm deep and have a 150 nm minimum width. Chemical mechanical polishing is utilized to achieve global planarization. The superior diode leakage and gate oxide (tox=55 Å) performance, excellent metal–oxide–semiconductor field effect transistor characteristics, and robust latch-up behavior demonstrated by this trench isolation technology, present it as a key enabler for continued scaling of semiconductor technologies. The experimental data presented predicts that with careful attention to process integration, trench isolation can be scaled well into the sub-0.25 μm size scale.
Surface processes occurring on TiSi2 and CoSi2 in fluorine-based plasmas: Afterglow of a NF3 plasma
Authors: Baklanov M. R. , Vanhaelemeersch S. , Storm W. , Vandervorst W. , Maex K.
Published: July 2002

The kinetics of surface processes occurring on TiSi2 and CoSi2 thin films in the afterglow of a NF3 plasma are studied. Analysis of the silicide surfaces by x-ray photoelectron spectroscopy and ellipsometry shows that a metal fluoride film forms during NF3 treatment. The thickness of the metal fluoride film on top of CoSi2 at 280–373 K and TiSi2 at T<300 K versus time is described by a parabolic law. The interaction of the silicides with the NF3 plasma in these regions is dominated by the diffusion of fluorine through the metal fluoride film. In the case of TiSi2 at T>300 K, the influence of the TiF4 desorption becomes important. Both Co and Ti fluorides are completely removed in a H2SO4/H2O2 mixture. After this treatment the silicide surface contains only 3–4 nm of silicon dioxide. Based on insight obtained in the fluorination process, the equations describing both the kinetics of CoSi2 and TiSi2 etching and the change of selectivity of SiO2 etching towards the silicides are explained.
Effect of lubricant coating on tips in atomic force microscopy
Authors: Umemura Shigeru , Igarashi Masaru , Andoh Yasuko , Kaneko Reizo , Aizawa Shin-ichi , Noguchi Kazumi , Dekura Takateru , Toda Akitoshi
Published: July 2002

We show that a lubricant-coated tip produces less specimen damage when soft materials are observed by atomic force microscopy (AFM). We measured the adhesion force and obtained AFM images of bacteria flagella using the same silicon nitride tip untreated, cleaned, and lubricant coated (in that order). The results show that a lubricant coating reduces the adhesion force. This result and contact angle measurements for a lubricant-coated silicon nitride wafer show that the tip surface is made hydrophobic by the lubricant coating. Since the dominant factor in the adhesion force in air is water capillary force, the lubricant coating on a tip reduces the adhesion force and hence the specimen damage. A lubricant coating on the tip is effective for AFM imaging of soft materials, such as biological specimens.
Application of in situ reflectance monitoring to molecular beam epitaxy of vertical-cavity structures
Authors: Klem J. F. , Breiland W. G. , Fritz I. J. , Drummond T. J. , Lee S. R.
Published: July 2002

We have used normal-incidence reflectance to monitor the growth of molecular beam epitaxial films. Least-squares fitting of the single-wavelength reflectance over regions of constant film growth rate and composition allowed the determination of growth rate and the complex refractive index of the film at the growth temperature. For AlInGaAs materials employed in a 1.32 μm reflectance modulator device, we found that layer thicknesses of approximately 500 Å produced precise measurement of these parameters. A simple feedback control scheme based on these measurements was employed to control the wavelength of the room-temperature cavity mode resonance in these devices to approximately 0.2%.
Use of oxygen gas in diamond film growth for improving stress and crystallinity properties of an x-ray mask
Authors: Noguchi Hitoshi , Kubota Yoshihiro , Takarada Takayuki
Published: July 2002

In order to improve the properties, such as stress and crystallinity, of diamond films for use as x-ray masks, we have studied the effectiveness of the addition of O2 to a CH4/H2 gaseous mixture in magnetically enhanced microwave plasma chemical vapor deposition. As the O2 concentration was increased, diamond grain growth became more dominant over the nondiamond component and grain growth continued. As a result, stress shifted toward the tensile regime. We explain the mechanism of this diamond stress shift by using the stress generation model proposed by Chaudhari. Under the optimum deposition conditions, i.e., CH4/O2/H2=2.0/0.5/97.5 vol % at 920 °C, we obtained (111)-textured polycrystalline diamond, which had high crystallinity and improved stress properties. The average stress was 147 MPa (tensile) and the uniformity was less than or equal to +21.1%; −12.2% was achieved within a 50-mm-diam area for a 2.3-μm-thick film. The biaxial Young’s modulus was evaluated by the bulge test, and was found to be 1000±51 GPa. This diamond membrane caused little in-plane distortion-induced backetching, i.e., max (x,y)=(27,31) nm, due to its high biaxial Young’s modulus.
Molecular beam epitaxial growth of InAs on a (311)A corrugated surface: Growth mechanism and morphology
Authors: Lubyshev D. I. , Micovic M. , Miller D. L. , Chizhov I. , Willis R. F.
Published: July 2002

Kinetic molecular beam epitaxy growth processes and the structure of the InAs (311)A surface were investigated in situ by reflection high energy electron diffraction (RHEED) and ex situ by low energy electron diffraction (LEED) and scanning tunneling microscopy (STM). Two stable surface structures, (2×15) and (1×5), were observed by RHEED on as-grown surfaces. RHEED oscillations have a strong azimuthal anisotropy with maximum amplitude in the [2̄33] direction and minimum amplitude in the [011̄] direction, suggesting that this surface grows via propagation and coalescence of pronounced two dimensional nuclei along the [2̄33] azimuth. Ex situ LEED and STM studies of the As-capped InAs (311)A surfaces confirmed the strong anisotropy of the surface structure. A characteristic feature of the LEED patterns is the degeneration of the principal diffraction into streaks along the [011̄] direction. STM images show rows running along the [2̄33] direction. Although the spacing between the rows varies, there are local areas showing lateral periodicities of ∼2.15 nm [(1×5) structure] and ∼6.45 nm [(2×15) structure] along the [011̄] direction, consistent with RHEED observations.
Direct imaging of the evolving Au/InSb(111) B interface
Authors: Mishima Tetsuya , Nakamura Jun , Tsukada Kenji , Nishizawa Masayasu , Eguchi Toyoaki , Osaka Toshiaki
Published: July 2002

In situ high-resolution transmission electron microscopy in the profile geometry has been used to observe the evolving features of the Au/InSb(111) B-(2×2) interface. During Au deposition in the range between 0 monolayer (ML) and ∼1 ML coverage, the outermost Sb-trimer layer of the InSb(111) B-(2×2) substrate changes in contrast, presumably revealing that deposited Au atoms are partially captured into it. At ∼2 ML coverage, an unknown phase emerges on the outermost layer, beyond which it continues to grow epitaxially in an island state, causing partial disruption of the substrate. The phase is identified as Au9In4 alloy with a γ-brass structure determined from a digital Fourier transform diffractogram and a transmission electron diffraction pattern. The epitaxial relationship of Au9In4 with the substrate is given by (111) InSb∥(111) Au9In4 and [11̄0] InSb∥[11̄0] Au9In4. The high resolution-profile transmission electron microscopy images of this alloy agree well wITH the results calculated by the multislice method.
End-point detection using focused ion beam-excited photoemissions in milling deep small holes in large scale integrated circuit structures
Authors: Yamaguchi Hiroshi , Saitoh Keiya , Mizumura Michinobu
Published: July 2002

An experimental instrument was made for the end-point detection of a deep small hole milled in large scale integrated circuit using focused ion beam (FIB). The SCANIIR method using photon-counting technique is adopted for detecting a very weak photoemission. The objective lens and imaging lens made by a quartz single lens are arranged in a parallel beam configuration. Observing optics, XY stage and Z controlling mechanism for the optics are also used. To avoid the noise from the wall of the hole, a blanking circuit for detected signals was used. Experiments using a wide angle objective optical system showed an aluminum layer lower than 10 μm and the SiO2 layer below were able to be clearly discriminated.
Direct current circuit simulation model for a field emission triode
Authors: Lu Chih-Wen , Lee Chung Len
Published: July 2002

A simple empirical circuit model, which can be incorporated into circuit simulation programs such as SPICE, for a field emission triode is developed. The model is based on the Fowler-Nordheim (FN) J-E relationship but takes into account the space charge effect and the exponential-like charge distribution on the surface of the tip of the device. A procedure is also developed to extract the parameters of the model.
Titanium nitride prepared by plasma-based titanium-ion implantation
Authors: Yukimura Ken , Sano Masanori , Maruyama Toshiro , Kurooka Shunji , Suzuki Yasuo , Chayahara Akiyoshi , Kinomura Atsushi , Horino Yuji
Published: July 2002

By using a titanium dc arc of 70 A with a pulse modulator with specifications of 60 kV/2.5 A/30 μs, titanium nitride (TiN) films were prepared on a silicon substrate (n-n+, [111],  400 μm in thickness) and titanium ions were simultaneously implanted by applying voltages of 20–50 kV of negative polarity to the substrate. The crystal orientation of the film produced by pulsed voltage application in plasma-based ion implantation (PBII) is different from that prepared by applying dc bias of −500 V. It is strongly (200) preferred orientation for PBII, while it is (111) and (220) preferred orientations for the dc bias. The film hardness increases with increasing pulse voltage, and the hardness for the application of −40 kV pulse is almost equal to that for the dc bias. Thus, the hardness maintains the same value while the crystal orientation differs from that for the dc bias.
System performance modeling of extreme ultraviolet lithographic thermal issues
Authors: Spence P. A. , Gianoulakis S. E. , Moen C. D. , Kanouff M. P. , Fisher A. , Ray-Chaudhuri A. K.
Published: July 2002

Numerical simulation is used in the development of an extreme ultraviolet lithography Engineering Test Stand. Extensive modeling was applied to predict the impact of thermal loads on key lithographic parameters such as image placement error, focal shift, and loss of CD control. We show that thermal issues can be effectively managed to ensure that their impact on lithographic performance is maintained within design error budgets.
Synchrotron light as a source for extreme ultraviolet lithography
Authors: Ockwell D. C. , Crosland N. C. E. , Kempson V. C.
Published: July 2002

In August 1998 a new European research program named Extreme Ultraviolet Concept Lithography Development System (EUCLIDES) was started. The program headed by ASM Lithography (ASML), partnered by Carl Zeiss and Oxford Instruments is evaluating extreme ultraviolet (EUV) light as a viable lithographic solution for resolutions of 70 nm and below. Oxford Instruments has investigated various options to use as synchrotron light sources: bending magnets, undulators, and wigglers. Output characteristics are given in terms of angular distribution and power spectrum. It will be explained wigglers are the preferred synchrotron light. The outline design of the storage ring is presented. The lattice is reviewed together with the light output properties and space requirements. How these drive the cost of ownership is addressed. Finally a brief comparison is made between this and the alternative (laser plasma) sources for EUV.
Fabrication of tunable antidot structures with submicron airbridges
Authors: Feng Y. , Sachrajda A. S. , Zawadzki P. , Kolind S. , Buchanan M. , Smet J. H. , Lapointe J. , Marshall P. A.
Published: July 2002

Two different electron sensitive polymers, polymethylglutarimide and polymethylmethacrylate were employed to form submicron Au airbridges for use in mesoscopic devices. A series of test devices was fabricated in which this technique was used to make electrical contact to a submicron elliptical gate placed within a quantum point contact. The airbridge was patterned by electron beam lithography and metal lift-off. Conductance measurements were performed on the devices at low magnetic fields. The results confirmed both the presence of the elliptical antidot as a negative voltage was applied to the center gate, as well as the nonintrusive nature of the airbridge.
Nanofabrication with deep-ultraviolet lithography and resolution enhancements
Authors: Fritze M. , Palmateer S. , Maki P. , Knecht J. , Chen C. K. , Astolfi D. , Cann S. , Denault S. , Krohn K. , Wyatt P.W.
Published: July 2002

This work explores the nanofabrication potential of resolution-enhanced deep-ultraviolet lithography. We combine strong phase-shift methods with fabrication-based enhancements to produce silicon structures in the deep sub-100 nm regime. Limits on resolution and pitch with these methods are considered.
Study of bilayer silylation process for 193 nm lithography using chemically amplified resist
Authors: Satou I. , Kuhara K. , Endo M. , Morimoto H.
Published: July 2002

The top surface imaging process has been studied in order to extend the limit of photolithography down to 0.10 μm or smaller dimensions using 193 nm or shorter wavelengths. We have been evaluating a bilayer silylation process as one of the approaches to improve the lithographic performance of the silylation process. In this article, we focus on the critical dimension controllability of the bilayer silylation process using a chemically amplified (CA) resist. The application of a CA resist is thought to be one of the promising approaches to increase the photospeed of the silylation process for practical applications. We investigated the effect of process issues due to the CA resist, and evaluated the lithographic performance of this silylation process. The 0.13 μm line and space (L/S) patterns were generated by 5 mJ/cm2 exposure energy, and the 0.11 μm L/S patterns could be generated without using any resolution enhancement techniques. Moreover, by applying an off-axis illumination exposure technique using an attenuated phase shift mask, the 0.10 μm L/S patterns were successfully fabricated with a sufficient process window.
Pattern resolution of an x-ray beamline with a wide exposure field
Authors: Khan Mumit , Cerrina Franco , Toyota Eijiro
Published: July 2002

In an exposure field for x-ray lithography, the beam spectrum is not always the same over the field because of beam path difference, even if the power distribution is uniform. The trend becomes obvious as the field size increases. The spectral change causes critical dimension (CD) variation and degrades pattern resolution. In this article we evaluate the effect of spectral change on CD variation for a 50×50 mm exposure field with 100 nm CD patterning. Additionally, we examine the thermal displacement of the mask during beam scanning and its effect on the CD variation. We find that the heating displacement contributes a negligible amount to CD variation.
Quantitative surface area evaluation of rugged polycrystalline Si plate for dynamic random access memory capacitor by xenon adsorption
Authors: Yanazawa Hiroshi , Futase Takuya , Suzuki Isao
Published: July 2002

The idea of rugged polycrystalline Si plate to increase dynamic random access memory capacitor is now going to be realized in mass production. Effective surface areas of polycrystalline Si films were evaluated by measuring xenon adsorption before and after surface roughened process. The surface area was increased by 1.8 times due to roughened process. This result is consistent with the value of 2.1 obtained from capacitance measurements on the samples prepared under the same condition. This work shows the applicability of ultrahigh sensitive gas adsorption to thin film surface characterization. Gas adsorption gives a new quantitative measure for analyzing surface morphology in addition to the qualitative observations by scanning electron microscopy and atomic force microscopy.
High-throughput, high-spatial-frequency measurement of critical dimension variations using memory circuits as electrical test structures
Authors: Ouyang X. , Deeter Timothy L. , Berglund C. N. , McCord Mark A. , Pease R. F. W.
Published: July 2002

Critical dimension (CD) errors are traditionally specified and characterized without reference to their spatial frequency spectra. However, a given amplitude of CD variation can have very different consequences depending on its spectrum. CD errors whose variation is over a few micrometers can be much more serious than those of the same magnitude that extend over several chips. Existing CD metrology tools, such as scanning electron microscopy or electrical resistance measurements, are seldom used to characterize these short-range CD variations, particularly those with spatial wavelengths below 100 μm, because of the large amount of data required and the difficulty of collecting data in such a dense grid. We report a new method of measuring CD variations using static random-access memory (SRAM) circuits in which direct measurements of bit-line currents reveal the individual transistor gate length variations within each memory cell. With the compactness and regularity of the SRAM layout we can measure CD variations with spatial periodicities down to 6 μm. By repeatedly measuring each cell in a memory chip and recording the corresponding currents we can achieve sufficient data to minimize noise, and through two-dimensional bandpass filtering 0.2 nm CD variations can be detected. Two designs of 4 Mbit SRAMs fabricated using 250 nm design rules were studied. The resulting CD variations yielded spectra that were dominated by peaks whose origins included uncorrected electron beam and optical proximity effects. Pattern-independent variations ascribable to the reticle generator itself appeared to contribute only a small fraction of the total error observed.
High-aspect-ratio nanophotonic components fabricated by Cl2 reactive ion beam etching
Authors: Zubrzycki W. J. , Vawter G. A. , Wendt J. R.
Published: July 2002

We describe highly anisotropic reactive ion beam etching of nanophotonic structures in AlGaAs based on the ion beam divergence angle and chamber pressure. The divergence angle is shown to influence the shape of the upper portion of the etch while the chamber pressure controls the shape of the lower portion. Deeply etched distributed Bragg reflectors are etched to an aspect ratio of 8:1 with 100 nm trench widths. The profile of the grating etch is straight with smooth sidewalls, flat bottoms, and squared corners. Two-dimensional photonic crystal post arrays are fabricated with smooth and vertical sidewalls, with structures as small as 180 nm in diameter and 2.0 μm in height.
Mechanical and thermal modeling of the SCALPEL mask
Authors: Martin C. J. , Semke W. H. , Dicks G. A. , Engelstad R. L. , Lovell E. G. , Liddle J. A. , Novembre A. E.
Published: July 2002

Scattering with angular limitation projection electron-beam lithography (SCALPEL) is being developed by Lucent Technologies for sub-130 nm lithography. The mask fabrication and exposure processes produce mask distortions that result in pattern placement errors. In order to understand these distortions, and determine how to reduce them to levels consistent with the error budget, structural and heat transfer finite element models have been generated to simulate the mechanical and thermal response of the mask. In addition, sensitivity studies of the distortions due to key design parameters that may be used to refine the SCALPEL mask configuration have been conducted.
Near-field polarization states and optical images in transmission mode through different surface structures
Authors: Wang S.
Published: July 2002

We provide a theoretical study of the near-field optical image of a homogeneous dielectric surface with deterministic sub-wavelength structures. Numerical simulations for different shapes of the sample are performed at constant-height mode with normal incidence. Near-field polarization states have been calculated by analyzing the difference of the transmitted intensities of p- and s-polarized light. We show that the near-field intensity depends more stronger on the feature form than the feature size. However, the polarization property is more sensitive to the shape of the sample rather than the distance of detection.
Correlation between agglomeration of a thin film and reflow filling in a contact hole for sputtered Al films
Authors: Shingubara S. , Kotani H. , Sakaue H. , Nishiyama F. , Takahagi T.
Published: July 2002

Al reflow filling in contact holes by annealing after Al deposition at room temperature was investigated with relation to agglomeration properties of very thin films. A strong correlation between filling achievement and agglomeration property was observed when the underlayer TiN film property was changed. When rapid thermal nitridation (RTN) was carried out after reactive sputtering of TiN, excellent filling in submicron contact holes was achieved at annealing temperatures around 400 °C for the case of thick Al film, and agglomeration into small islands was observed for thin Al films. The activation energy of atomic mass transport for the filling process was 0.36 eV, which suggests a surface diffusion dominated filling process. On the other hand, when no RTN was carried out for TiN, reflow filling was achieved at temperatures around 600 °C which were close to the melting point of Al, and agglomeration into islands in thin films was suppressed at 400 °C. The activation energy of the latter case was 0.90 eV, which was between those of lattice diffusion and grain boundary diffusion. The correlation between filling achievement and agglomeration is ascribed to a large surface diffusion atomic flux in the case with RTN.
Novel process integration for reduction of subquarter-micron contact resistance
Authors: Ku Victor
Published: July 2002

In this article, etching of subquarter-micron contact holes with a film structure of silicon dioxide (SiO2)/silicon nitride (Si3N4)/silicide (TiSix) in dual-frequency capacitively coupled plasmas is investigated. The etch process scheme here uses a highly selective chemistry to remove SiO2 film first, then the process switches to another chemistry with high etch selectivity of Si3N4-to-TiSix. The author found that the polymer film deposited inside contact holes during SiO2 etching severely degraded the selectivity of Si3N4-to-TiSix. This can cause open or high contact resistance. Different process integration schemes with the goal of increasing the etch selectivity of Si3N4-to-TiSix were initiated and developed. Electrical parametric data of contact chain resistance will be presented.
Effect of material variations on performance of double-recessed gate power pseudomorphic high electron mobility transistors in monolithic microwave and millimeter wave integrated circuit applications
Authors: Hussain T. , Chu P. , Wen C. P. , Circle M. , Gomez A. , Midford T. , Cisco T.
Published: July 2002

We report the effect of start epi-material variability on the performance of double-recessed power pseudomorphic high electron mobility transistors. Variation in channel-recess depth, which is related to variation in the start material, is critically linked to rf performance of monolithic microwave and millimeter wave integrated circuit high power amplifiers. For high yield, it is important to control the channel recess, which in turn has implications on acceptable variation in epi-material. Design tweaks can relax channel-recess tolerance limits, but it is still important to account for material variation.
Microscopic Structure of the Metal-Insulator Transition in Two Dimensions
Authors: Ilani S. , Yacoby A. , Mahalu D. , Shtrikman Hadas
Published: July 2002

A single electron transistor is used as a local electrostatic probe to study the underlying spatial structure of the metal-insulator transition in two dimensions. The measurements show that as we approach the transition from the metallic side, a new phase emerges that consists of weakly coupled fragments of the two-dimensional system. These fragments consist of localized charge that coexists with the surrounding metallic phase. As the density is lowered into the insulating phase, the number of fragments increases on account of the disappearing metallic phase. The measurements reveal that the metal-insulator transition is a result of the microscopic restructuring that occurs in the system.
Evidence for Dust Grain Growth in Young Circumstellar Disks
Authors: Throop Henry B. , Bally John , Esposito Larry W. , McCaughrean Mark J.
Published: July 2002

Hundreds of circumstellar disks in the Orion nebula are being rapidly destroyed by the intense ultraviolet radiation produced by nearby bright stars. These young, million-year-old disks may not survive long enough to form planetary systems. Nevertheless, the first stage of planet formation—the growth of dust grains into larger particles—may have begun in these systems. Observational evidence for these large particles in Orion's disks is presented. A model of grain evolution in externally irradiated protoplanetary disks is developed and predicts rapid particle size evolution and sharp outer disk boundaries. We discuss implications for the formation rates of planetary systems.
Consequences of the Unresolvable
Authors: Gribbin John
Published: July 2002

From Certainty to Uncertainty
The Story of Science and Ideas in the Twentieth Century. F. David Peat. Joseph Henry (National Academy Press), Washington, DC, 2002. 248 pp. $24.95. ISBN 0-309-07641-2.

Writing for a general audience, Peat discusses scientific, philosophical, and cultural responses to the overthrow of Newton's clockwork universe and the rise of relativity, quantum mechanics, and chaos theory.
Shock Melting of the Canyon Diablo Impactor: Constraints from Nickel-59 Contents and Numerical Modeling
Authors: Schnabel C. , Pierazzo E. , Xue S. , Herzog G. F. , Masarik J. , Cresswell R. G. , di Tada M. L. , Liu K. , Fifield L. K.
Published: July 2002

Two main types of material survive from the Canyon Diablo impactor, which produced Meteor Crater in Arizona: iron meteorites, which did not melt during the impact; and spheroids, which did. Ultrasensitive measurements using accelerator mass spectrometry show that the meteorites contain about seven times as much nickel-59 as the spheroids. Lower average nickel-59 contents in the spheroids indicate that they typically came from 0.5 to 1 meter deeper in the impactor than did the meteorites. Numerical modeling for an impact velocity of 20 kilometers per second shows that a shell 1.5 to 2 meters thick, corresponding to 16 percent of the projectile volume, remained solid on the rear surface; that most of the projectile melted; and that little, if any, vaporized.
Detection of Resistance to Amphotericin B in
Candida
Isolates by Using Iso-Sensitest Broth
Authors: Cuenca-Estrella Manuel , Dı́az-Guerra Teresa M. , Mellado Emilia , Rodrı́guez-Tudela Juan L.
Published: July 2002

A major limitation of the National Committee for Clinical Laboratory Standards M27-A methodology is reliable detection of amphotericin B (AMB) resistance. The results obtained by using Iso-Sensitest, a synthetic medium, to detect AMB resistance were analyzed and compared with those obtained with RPMI and antibiotic medium 3 (AM3). The ability to detect AMB resistance with RPMI is not enhanced by using a higher inoculum, glucose supplementation at a final concentration of 20 g/liter, spectrophotometric reading, or 24 h of incubation time. Testing using AM3 and an inoculum of 10
3
CFU/ml detects resistance. Identification of resistant isolates is not improved by glucose supplementation, changes in reading method, or changes in incubation time. However, the use of AM3 as assay medium and an inoculum of 10
5
CFU/ml did not allow detection of AMB resistance. Testing using Iso-Sensitest medium appears to be similar to AM3 in detecting resistance. The most pronounced discrimination is achieved by testing in Iso-Sensitest supplemented with glucose and spectrophotometric reading after 24 h of incubation. The reproducibility of MIC testing was greatest for Iso-Sensitest-based procedures. Use of Iso-Sensitest produces both highly reproducible MICs and reliable identification of AMB-resistant
Candida
isolates.
Inhibition of a Glucose-Limited Sequencing Fed-Batch Culture of
Salmonella enterica
Serovar Enteritidis by Volatile Fatty Acids Representative of the Ceca of Broiler Chickens
Authors: van der Wielen Paul W. J. J. , Biesterveld Steef , Lipman Len J. A. , van Knapen Frans
Published: July 2002

The effects of concentrations of volatile fatty acids on an anaerobic, glucose-limited, and pH-controlled growing culture of
Salmonella enterica
serovar Enteritidis were studied. Suddenly increasing volatile fatty acids to the concentrations representative of the ceca of 15-day-old broiler chickens caused washout of serovar Enteritidis. In contrast, a sudden increase to the volatile fatty acid concentrations representative of the ceca of younger broiler chickens caused a reduction in the biomass but not washout. Gradually increasing volatile fatty acids caused a gradual decrease in the biomass of serovar Enteritidis. We conclude that the concentrations of volatile fatty acids present in the ceca of broilers with a mature microflora can cause washout of serovar Enteritidis in an in vitro system mimicking cecal ecophysiology.
Modulation of B-Cell Proliferative Response by a Soluble Extract ofNippostrongylus brasiliensis
Authors: Ehigiator Humphrey N. , Stadnyk Andrew W. , Lee Timothy D. G.
Published: July 2002

We and others have previously shown that nematodes or nematode products can stimulate or inhibit the generation of lymphocyte responses, suggesting that nematodes exert diverse effects on the developing immune responses of their host. In this study we examined the immunomodulatory effect of a soluble extract ofNippostrongylus brasiliensis(adult worm homogenate [AWH]) on B-cell responsiveness. We found that the extract inhibited the proliferation of B cells to lipopolysaccharide (LPS) stimulation in a dose-dependent manner. This effect was specific to B cells, since the extract did not inhibit T-cell proliferation to concanavalin A or anti-CD3 stimulation. The data presented here confirm that the extract is not toxic to B cells. We present evidence that the active factor is proteinaceous in nature and that the inhibitory activity is restricted to the adult stage ofNb. The extract does not appear to interfere with early activation events since it can be added up to 48 h after LPS stimulation, and it inhibited responses to phorbol myristate acetate and ionomycin. Furthermore, the proliferation of B cells to other activators was also inhibited by AWH. This observation shows that the inhibitory activity of AWH is not restricted to LPS-mediated B-cell proliferation. We present evidence that, in the absence of accessory cells, the inhibitory effect of the extract was ablated. This observation shows that the activity of AWH is not mediated directly on B cells but is mediated via the production of negative signals from accessory cells (macrophages), which affect a downstream pathway required by all B-cell activators tested. These effects on B-cell and accessory cell function are likely to have a significant effect on the outcome of infections experienced concurrently.
Neisseria gonorrhoeaePorin Modifies the Oxidative Burst of Human Professional Phagocytes
Authors: Lorenzen Dirk R. , Günther Dirk , Pandit Jasmine , Rudel Thomas , Brandt Ernst , Meyer Thomas F.
Published: July 2002

A hallmark of infection with the gram-negative bacteriumNeisseria gonorrhoeaeis the local infiltration and subsequent activation of polymorphonuclear neutrophils. Several gonococcal outer membrane proteins are involved in the interaction with and the activation of these phagocytes, including gonococcal porin, the most abundant protein in the outer membrane. Previous work suggests that this porin plays a role in various cellular processes, including inhibiting neutrophils activation and phagosome maturation in professional phagocytes. Here we investigated the ability of porin to modify the oxidative metabolism of human peripheral blood neutrophils and monocytes in response to particulate stimuli (including live gonococci) and soluble agents. The activation of the oxidative metabolism was determined by chemiluminescence amplified with either luminol or lucigenin. We found that treatment of the phagocytes with porin inhibits the release of reactive oxygen species measured as luminol-enhanced chemiluminescence in response to zymosan, latex particles, and gonococci. The engulfment of these particles was not, however, affected by porin treatment. Similar effects of porin on the chemiluminescence response were observed in cytochalasin B-treated neutrophils exposed to the soluble chemotactic peptideN-formylmethionyl-leucyl-phenylalanine. This indicates that porin selectively inhibits granule fusion with those cellular membranes that are in direct contact with porin, namely, the phagosomal and plasma membranes. This porin-induced downregulation of oxidative metabolism may be a potent mechanism by which gonococci modulate oxygen-dependent reactions by activated phagocytes at inflammation sites.
TonB Is Required for Intracellular Growth and Virulence ofShigella dysenteriae
Authors: Reeves Stephanie A. , Torres Alfredo G. , Payne Shelley M.
Published: July 2002

To assess the importance of TonB-dependent iron transport systems to growth ofShigellain vivo, atonBmutant ofShigella dysenteriaewas isolated and tested in cultured cells. ThetonBmutant invaded epithelial cells, but did not form plaques in confluent monolayers of Henle cells, indicating an inability of this mutant to spread from cell to cell. The rate of intracellular multiplication of thetonBmutant was reduced significantly compared to that of the wild type. The loss of virulence in thetonBmutant was not due to loss of either Shu or Ent, the TonB-dependent systems which allow for transport of heme and ferrienterobactin, respectively. AshuAmutant lacking the outer membrane receptor for heme, anentBmutant defective in enterobactin synthesis, and ashuA entBdouble mutant each were able to invade cultured cells, multiply intracellularly, and form wild-type plaques. The ability ofS. dysenteriaeto access iron during intracellular growth was assessed by flow cytometric analysis of an iron- and Fur-regulatedshuA-gfpreporter construct. Low levels of green fluorescent protein expression in the intracellular environment were observed in all strains, indicating that iron is available to intracellular bacteria, even in the absence of TonB-dependent iron transport. The failure of thetonBmutant to grow well in an iron-replete intracellular environment suggests that TonB plays a role in addition to heme- and siderophore-mediated iron acquisition in vivo, and this function is required for the intracellular growth and intercellular spread ofS. dysenteriae.
Characterization of the Catalytic Domain of
Clostridium novyi
Alpha-Toxin
Authors: Busch Christian , Schömig Kathrin , Hofmann Fred , Aktories Klaus
Published: July 2002

Clostridium novyi
alpha-toxin belongs to the family of large clostridial cytotoxins which act on cells through the modification of small GTP-binding proteins. We present here an analysis of the catalytic domain of alpha-toxin. A NH
2
-terminal 551-amino-acid fragment, α551, was found to contain the full enzyme activity of the holotoxin, whereas a slightly shortened fragment encompassing 509 amino acids showed no detectable enzyme activity. Further characterization of the enzymatically active fragment α551 revealed a substrate specificity for both UDP–
N
-acetylglucosamine and UDP-glucose. A Michaelis-Menten constant of 17 μM was determined for the substrate UDP–
N
-acetylglucosamine, while that for UDP-glucose was about 20 times higher, indicating a weaker affinity of the toxin for the latter substrate. Mutation of the aspartic acids of a conserved motif DXD within α551 reduced enzyme activity >700-fold and inhibited cytotoxicity after microinjection in cells. Inhibition of enzyme activity of the DXD mutant could be partially overcome by increased concentrations of manganese ions, suggesting the involvement of these aspartic acids in Mn
2+
binding. By construction of chimeras of enzymatically active fragments of
C. sordellii
lethal toxin and
C. novyi
alpha-toxin, we located the region involved in nucleotide-sugar specificity to amino acids 133 through 517.
Key Role for DsbA in Cell-to-Cell Spread of
Shigella flexneri
, Permitting Secretion of Ipa Proteins into Interepithelial Protrusions
Authors: Yu Jun , Edwards-Jones Bryn , Neyrolles Olivier , Kroll J. Simon
Published: July 2002

DsbA, a disulfide bond catalyst, is necessary for realization of the pathogenic potential of
Shigella flexneri
. Sh42, a mutant strain differing from wild-type M90TS solely because it expresses nonfunctional DsbA33G (substitution for 33C at the active site), secreted less IpaB and IpaC than M90TS in response to various stimuli in vitro. A kinetic study demonstrated that Sh42 responded more slowly to Congo red than M90TS. By modulating relative concentrations of functional and nonfunctional DsbA within bacteria, functional enzyme has been shown to be necessary for intercellular spread. By confocal microscopy, M90TS dividing in protrusions was shown to secrete Ipa proteins from the septation furrow, anticipating lysis of protrusions, while Sh42 showed minimal Ipa secretion in this location. In the light of a previous demonstration that DsbA is not necessary for entry of epithelial cells, we conclude that a role in virulence of this disulfide bond catalyst lies in facilitating secretion of Ipa proteins specifically within epithelial protrusions, in turn allowing cell-to-cell spread of
S. flexneri.
Evidence for Vaccine Synergy between
Borrelia burgdorferi
Decorin Binding Protein A and Outer Surface Protein A in the Mouse Model of Lyme Borreliosis
Authors: Hanson Mark S. , Patel Nita K. , Cassatt David R. , Ulbrandt Nancy D.
Published: July 2002

Mice immunized with either the predominantly vector-stage lipoprotein outer surface protein A (OspA) or the in vivo-expressed lipoprotein decorin binding protein A (DbpA) are protected against
Borrelia burgdorferi
challenge. DbpA-OspA combinations protected against 100-fold-higher challenge doses than did either single-antigen vaccine and conferred significant protection against heterologous
B. burgdorferi
,
B. garinii
, and
B. afzelii
isolates, suggesting that there is synergy between these two immunogens.
Latency-Associated Peptide of Transforming Growth Factor β Enhances Mycobacteriocidal Immunity in the Lung duringMycobacterium bovisBCG Infection in C57BL/6 Mice
Authors: Wilkinson K. A. , Martin T. D. , Reba S. M. , Aung H. , Redline R. W. , Boom W. H. , Toossi Z. , Fulton S. A.
Published: July 2002

Latency-associated peptide of transforming growth factor β (TGF-β) (LAP) was used to determine whether in vivo modulation of TGF-β bioactivity enhanced pulmonary immunity toMycobacterium bovisBCG infection in C57BL/6 mice. LAP decreased BCG growth in the lung and enhanced antigen-specific T-cell proliferation and gamma interferon mRNA expression. Thus, susceptibility of the lung to primary BCG infection may be partially mediated by the immunosuppressive effects of TGF-β.
Binding and Activation of Human Plasminogen by
Mycobacterium tuberculosis
Authors: Monroy Verónica , Amador Angelica , Ruiz Blanca , Espinoza-Cueto Patricia , Xolalpa Wendy , Mancilla Raul , Espitia Clara
Published: July 2002

The first evidence of the interaction of
Mycobacterium tuberculosis
with the plasminogen system is herein reported. By FACScan analysis and affinity blotting, lysine-dependent binding of plasminogen to
M. tuberculosis
was demonstrated. The binding molecules were 30-, 60-, and 66-kDa proteins present in cell wall and soluble protein extracts. The activation of plasminogen, which occurred only in presence of fibrin and was not inhibited by the host serpin, α
2
-antiplasmin, was also demonstrated.
Lack of Regulation of the Modification-Dependent Restriction Enzyme McrBC in
Escherichia coli
Authors: Murphy Mark , Schmid Nuoffer Stefanie , Bickle Thomas A.
Published: July 2002

Restriction alleviation (RA) by the type I restriction enzyme
Eco
KI is caused by treatments that damage DNA. RA is due to proteolysis of the
Eco
KI HsdR subunit by the ClpXP ATP-dependent protease. Here we show that the modification-dependent enzyme McrBC is not subject to RA, although it is moderately sensitive to ClpAP.
The Minimal Replicator of Epstein-Barr Virus
oriP
Authors: Yates John L. , Camiolo Sarah M. , Bashaw Jacqueline M.
Published: July 2002

oriP
is a 1.7-kb region of the Epstein-Barr virus (EBV) chromosome that supports the replication and stable maintenance of plasmids in human cells.
oriP
contains two essential components, called the DS and the FR, both of which contain multiple binding sites for the EBV-encoded protein, EBNA-1. The DS appears to function as the replicator of
oriP
, while the FR acts in conjunction with EBNA-1 to prevent the loss of plasmids from proliferating cells. Because of EBNA-1's role in stabilizing plasmids through the FR, it has not been entirely clear to what extent EBNA-1 might be required for replication from
oriP
per se, and a recent study has questioned whether EBNA-1 has any direct role in replication. In the present study we found that plasmids carrying
oriP
required EBNA-1 to replicate efficiently even when assayed only 2 days after plasmids were introduced into the cell lines 143B and 293. Significantly, using 293 cells it was demonstrated that the plasmid-retention function of EBNA-1 and the FR did not contribute significantly to the accumulation of replicated plasmids, and the DS supported efficient EBNA-1-dependent replication in the absence of the FR. The DS contains two pairs of closely spaced EBNA-1 binding sites, and a previous study had shown that both sites within either pair are required for activity. However, it was unclear from previous work what additional sequences within the DS might be required. We found that each “half” of the DS, including a pair of closely spaced EBNA-1 binding sites, had significant replicator activity when the other half had been deleted. The only significant DNA sequences that the two halves of the DS share in common, other than EBNA-1 binding sites, is a 9-bp sequence that is present twice in the “left half” and once in the “right half.” These nonamer repeats, while not essential for activity, contributed significantly to the activity of each half of the DS. Two thymines occur at unique positions within EBNA-1 binding sites 1 and 4 at the DS and become sensitive to oxidation by permanganate when EBNA-1 binds, but mutation of each to the consensus base, adenine, actually improved the activity of each half of the DS slightly. In conclusion, the DS of
oriP
is an EBNA-1-dependent replicator, and its minimal active core appears to be simply two properly spaced EBNA-1 binding sites.