bluuebunny/crossref_metadata_2025 huggingface dataset:
Approach for control of high-density plasma reactors through optimal pulse shaping
Authors: Vincent Tyrone L. , Raja Laxminarayan L.
Published: September 2002

Increasingly stringent requirements in the manufacture of integrated circuits and microscale devices are demanding new approaches to the design and operation of glow-discharge plasma process reactors. Several approaches have been proposed recently, one of which is the operation of plasma reactors in the pulsed mode where the power input to the reactor is modulated using square-wave pulses (SWPs). In this article, we propose a completely general technique for pulsed operation of plasma reactors where the power input is modulated using pulse shapes that are determined systematically using a computational method. We call this technique optimal pulse shaping (OPS) and it relies on a physical model of the plasma reactor used in conjunction with an optimal control algorithm. The OPS technique enables simultaneous control of several plasma process parameters, thus expanding the accessible plasma parameter space over that achievable by SWPs. We apply the OPS technique to a pure argon high-density plasma reactor. Optimal power input pulse shapes and pulsing frequencies are determined in order to control time-averaged values of the ion number densities, the ratio of metastable-to-ion number densities, and the electron temperatures in the bulk plasma. Results indicate that all optimal power input pulse shapes can be characterized by “on” and “off” periods, with a typical on period consisting of power input spikes accompanied by a lower plateau input. The off period consisting of either a true zero input power or a small input power. The power input spikes during the on period control the averaged ion densities, while the plateau input controls the metastable densities. The average electron temperature is controlled by the off power input.
Effect of deposition interruption and substrate bias on the structure of sputter-deposited yttria-stabilized zirconia thin films
Authors: Ruddell David E. , Stoner Brian R. , Thompson Jeffrey Y.
Published: September 2002

The possibility of altering the morphological structure of radio-frequency magnetron sputter- deposited yttria-stabilized zirconia thin films was studied. A columnar grain structure is often observed in sputter deposited thin films; however, this morphology may not be desirable. Two potential methods of disrupting the columnar grain structure were investigated; deposition interruption and periodic application of a substrate bias. Simple interruption of the deposition process was not effective in altering the columnar grain structure of the sputter-deposited films. The use of a periodic substrate bias produced a laminate structure with alternating layers of distinctly different microstructure. X-ray diffraction showed that as the thickness of the layers decreased (with increasing number of layers), the monoclinic phase was eliminated from the deposited thin films, and the films showed a preference for the (200)t orientation.
Ion energy distributions versus frequency and ion mass at the rf-biased electrode in an inductively driven discharge
Authors: Abraham I. C. , Woodworth J. R. , Riley M. E. , Miller P. A. , Hamilton T. W. , Aragon B. P.
Published: September 2002

In this article, we present ion energy distributions (IEDs) at a rf-biased surface as a function of driving frequency and ion mass. The experiments were carried out in high-density inductively coupled rare-gas (Ne,Ar,Xe) plasmas. Our quadrupole mass and cylindrical-mirror energy analyzer sampled ions incident on a rf-biased pinhole located in the center of the wafer chuck. The electron density, electron temperature, and plasma and chuck potential oscillations were measured, and they provided inputs to numerical models used to predict IEDs, which were shown to closely match our experimental results under certain conditions. For a given driving frequency, heavier ions showed narrower IEDs and, for a given ion mass, the IED became narrower and shifted to a higher mean energy with increased driving frequency, in agreement with calculations.
Effects of plasma treatment on the properties of Cu/Ta/fluorinated amorphous carbon (a-C:F)/Si multilayer structure
Authors: Yang Sung-Hoon , Kim Heondo , Park Jong-Wan
Published: September 2002

The effects of nitrogen postplasma treatment on the properties of a Cu/Ta/a-C:F structure were investigated. Interface reactions between Ta and a-C:F were also examined. A strong interaction between Ta and a-C:F at the interface and defluorination of a-C:F film occurred during Ta sputter deposition. Ta fluoride was observed at the interface between Ta and a-C:F, which led to adhesion and reliability problems. In order to suppress the reaction at the interface, nitrogen plasma was applied to the as-deposited a-C:F film. The fluorine concentration of the film surface decreases with plasma treatment. As the plasma treatment power increases, the adhesion between Ta and a-C:F film improved. From this study, it was found that nitrogen plasma treatment of a-C:F films is a very effective method for suppression of defluorination of a-C:F film and the interface reaction between Ta and a-C:F film.
Effects of deposition temperature on structural defect and electrical resistivity in heteroepitaxial La0.5Sr0.5CoO3/CeO2/YSZ/Si films
Authors: Chen Chun-Hua , Saiki Atsushi , Wakiya Naoki , Shinozaki Kazuo , Mizutani Nobuyasu
Published: September 2002

The effects of deposition temperature (500–800 °C) on the structural defect and electrical resistivity of heteroepitaxial La0.5Sr0.5CoO3 (LSCO) films with CeO2/YSZ double buffer layers on Si(001) substrates have been investigated mainly by high-resolution x-ray diffraction techniques. According to the deposition temperature range, two types of structural defect could be distinguished clearly. In the lower-temperature range of about 500–600 °C, the main defect of LSCO is the mosaic structure with a huge coherent distortion. In the higher range of about 600–800 °C, a distinct lattice constant gradient of LSCO was observed, indicating an occurrence of lattice relaxation when introducing an additional defect type, which are misfit dislocations. A high correlation between the electrical resistivity of LSCO, and the defect type and concentration was found. The distribution of electrical resistivity shows a mosaic dispersion degree dependence in 500–600 °C and a lattice relaxation degree dependence in 700–800 °C, where the mosaic dispersion degree and lattice relaxation degree can be estimated by the full width at half maxima of ω and 2θ/ω scans, respectively.
Effect of substrate position in i-ZnO thin-film formation to Cu(In,Ga)Se2 solar cell
Authors: Yamaguchi Toshiyuki , Tanaka Tooru , Yoshida Akira
Published: September 2002

Intrinsic ZnO (i-ZnO) thin films were prepared by rf magnetron sputtering of nondoped ZnO targets in Ar gas under various substrate positions and they were applied to solar cells. We have characterized i-ZnO thin films and investigated the solar cell performance. The resistivity and the full width at half maximum (FWHM) in the x-ray diffraction peak were changed, depending on the substrate position. The performance of solar cells was correspondent to the change of the resistivity and the FWHM of the i-ZnO thin films.
Quantitative study of ion bombardment induced phase transformation of cubic boron nitride by reflective electron energy-loss spectroscopy
Authors: Hui Y. Y. , Wong K. W. , Lau W. M.
Published: September 2002

The phase transformation of cubic boron nitride (c-BN) in the near-surface region of a c-BN (111) facet induced by argon-ion bombardment has been investigated by reflective electron energy-loss spectroscopy, with the objective of tracking possible growth mechanisms of c-BN in ion-assisted vapor deposition. For example, with an ion energy of 500 eV at a fluence of 5×1016 ions/cm2, 74% of c-BN were found transformed to h-BN and a-BN within the ion penetration depth of 11 Å. Lowering the argon ion bombardment energy to 200 eV reduced the phase transformation depth to 7 Å. A damage saturation was observed at a fluence of 6×1016 ions/cm2, at which up to 9% of the cubic phase were transformed. Similar measurements were performed at other ion energies. The present work gives a quantitative explanation of the difficulty in growing pure c-BN films with ion-assisted deposition and the presence of an upper-bound in ion energy above which the formation of phases other than the cubic phase dominate.
Simple method for cleaning gallium nitride (0001)
Authors: Machuca Francisco , Liu Zhi , Sun Yun , Pianetta P. , Spicer W. E. , Pease R. F. W.
Published: September 2002

Achieving clean surfaces is a major and challenging requirement for the study of surfaces and surface reactions. We describe the use of synchrotron radiation (SR) to probe the electronic structure of the gallium nitride (GaN) (0001) surface that has undergone wet chemical cleaning sequences followed by heating. By using SR in the range of 200–1000 eV the core levels of Ga, N, O, and C are monitored. Immersion in a 4:1 solution of sulfuric acid (51%) to hydrogen peroxide (30%) followed by a 700 °C (200 °C below decomposition temperature) vacuum anneal (⩽10−10 Torr) results in a reduction of carbon and oxygen coverage to a few percent of a monolayer. This suggests a weakly bound oxide of carbon being chemisorbed to the GaN surface after the sulfuric acid/hydrogen peroxide treatment and it is removed by the heating.
Growth of stoichiometric (002) ZnO thin films on Si (001) substrate by using plasma enhanced chemical vapor deposition
Authors: Li B. S. , Liu Y. C. , Zhi Z. Z. , Shen D. Z. , Zhang J. Y. , Lu Y. M. , Fan X. W. , Kong X. G.
Published: September 2002

ZnO thin films have been grown on Si(100) substrate by plasma enhanced chemical vapor deposition using a zinc organic source [Zn(C2H5)2] and carbon dioxide (CO2) gas mixture at 503 K. The dependence of ZnO thin film quality on the gas flow rate ratio of Zn(C2H5)2 to CO2 (GFRRZC) is studied by x-ray diffraction (XRD), optical absorption (OA) spectra, and photoluminescence (PL) spectra. An excitonic absorption peak is observed in the OA spectra, which closely depends on the GFRRZCs. The XRD spectra show that a c-axis-orientated wurtzite structure ZnO thin film with the full width at half maximum (FWHM) of 0.24° has been prepared. The PL spectra show a strong UV emission with a narrow FWHM of 105 meV at 3.289 eV with a weak deep-level defect emission around 2.5 eV, implying the formation of the stoichiometric ZnO thin films. The origin of the UV band is from the free exciton recombination testified by the temperature dependent PL spectra.
Thermal stability of arc evaporated high aluminum-content Ti1−xAlxN thin films
Authors: Hörling A. , Hultman L. , Odén M. , Sjölén J. , Karlsson L.
Published: September 2002

The thermal stability of Ti1−xAlxN films deposited by arc evaporation from Ti–Al cathodes with 67 and 75 at. % aluminum, respectively, has been investigated. The microstructure of as-deposited and isothermally annealed samples were studied using scanning electron microscopy, transmission electron microscopy, and x-ray diffraction. The chemical composition and elemental distribution were determined by energy dispersive x ray (EDX), Rutherford backscattering spectrometry, and EDX mapping. Transmission electron micrographs revealed a dense and columnar microstructure in the as-deposited condition. Films deposited from the 67 at. % cathodes were of cubic NaCl-structure phase, whereas films deposited from the 75 at. % cathodes exhibited nanocrystallites of wurzite-structure hexagonal-phase AlN in a cubic (c)-(Ti,Al)N matrix. Both films were stable during annealing at 900 °C/120 min with respect to phase composition and grain size. Annealing at 1100 °C of films deposited from the 67 at. % cathodes resulted in phase separation of c-TiN and h-AlN, via spinodal decomposition of c-TiN and c-AlN. (Ti,Al)N films undergo extensive stress relaxation and defect annihilation at relatively high temperatures, and aspects of these microstructural transformations are discussed.
Improvement of oxygen barrier of polyethylene terepthalate film by plasma-source ion implantation of carbon
Authors: Yoshida M. , Tanaka T. , Shinohara M. , Watanabe S. , Lee J. W. , Takagi T.
Published: September 2002

The surface of polyethylene terepthalate (PET) film has been successfully modified to amorphous carbon by plasma source ion implantation (PSII) as a means of improving the oxygen barrier characteristics of the PET film. The process was performed using high negative pulsed voltage in an radio frequency field with C2H2 gas. The amorphous carbon layer is found to consist primarily of graphite crystal with C–H, C–H2 and C–H3 components, and to reduce the oxygen transmission rate of the film by up to 100 times that of unmodified PET film at a thickness of only 70–300 nm. Raman spectra reveal that the amorphous carbon layer has diamond-like carbon characteristics, yet is soft compared to other diamond-like carbon films with hydrogen contents of >20 at. %. A stronger graphite character in the x-ray photoelectron spectroscopy spectra is found to represent the fineness of the carbon structure and correlate well with the improvement of oxygen barrier characteristics.
Angular dependence of SiO2 etch rate at various bias voltages in a high density CHF3 plasma
Authors: Lee Gyeo-Re , Hwang Sung-Wook , Min Jae-Ho , Moon Sang Heup
Published: September 2002

The dependence of the SiO2 etch rate on the angle of ions incident on the substrate surface was studied over a bias voltage range from −20 to −600 V in a high-density CHF3 plasma using a Faraday cage to control the ion incident angle. The effect of the bottom plane on the sidewall etching was also examined. Differences in the characteristics of the etch rate as a function of the ion angle were observed for different bias voltage regions. When the absolute value of the bias voltage was smaller than 200 V, the normalized etch rate (NER) defined as the etch rate normalized by the rate on the horizontal surface, changed following a cosine curve with respect to the ion incident angle, defined as the angle between the ion direction and the normal of the substrate surface. When the magnitude of the bias voltage was larger than 200 V, the NER was deviated to higher values from those given by a cosine curve at ion angles between 30° and 70°, and then drastically decreased at angles higher than 70° until a net deposition was observed at angles near 90°. The characteristic etch-rate patterns at ion angles below 70° were determined by the ion energy transferred to the surface, which affected the SiO2 etch rate and, simultaneously, the rate of removal of a fluorocarbon polymer film formed on the substrate surface. At high ion angles, particles emitted from the bottom plane contributed to polymer formation on and affected the etching characteristics of the substrate.
Epitaxial growth and dielectric properties of functionally graded (Ba1−xSrx)TiO3 thin films with stoichimetric variation
Authors: Zhu Xinhua , Lai-Wah Chan Helen , Choy Chung-Loong , Wong Kin-hung
Published: September 2002

Functionally graded (Ba1−xSrx)TiO3 (BST) thin films with stoichimetric variation (x:0.0–0.25) were layer-by-layer grown epitaxially on MgO (100) single-crystal substrates with 100-nm-thick conductive La0.5Sr0.5CoO3 (LSCO) as the bottom electrode by pulsed-laser deposition. X-ray diffraction, rocking curve, and φ scans showed that the graded films are epitaxial grown with an orientation of [001](100)BST//[001](100)MgO. The surface roughness of the up-graded film was larger than that of the down-graded films, and the full width at half maximum of the BST (200) rocking curve of up-graded films was wider than that of the down-graded films. The compositional gradations along the depth in the films were confirmed by Rutherfold backscattering spectroscopy. Dielectric properties measured by vertical structures using LSCO as the bottom electrodes showed that the dielectric constant and dielectric loss at 10 kHz were 532 and 0.010 for the up-graded films, and 715 and 0.0103 for the down-graded films, respectively. An enhanced dielectric behavior was observed in the down-graded films. The graded BST films also exhibit a broad and flat profile of the dielectric constant versus the temperature. Such behavior of the dielectric response is attributed to the presence of the compositional and/or residual strain gradients in the epitaxial graded films. The possible origins of the enhanced dielectric behavior observed in the down-graded films are also briefly discussed.
Neutral gas temperatures measured within a high-density, inductively coupled plasma abatement device
Authors: Tonnis Eric J. , Graves David B.
Published: September 2002

The neutral temperature within a cylindrical, inductively coupled plasma source has been studied for rare gas and molecular plasmas using the technique of optical emission thermometry. By adding small quantities of N2 to the gas feeds as an actinometer, the neutral temperature of the discharge can be estimated by simulation and fitting of the rotationally unresolved second positive band (C3Πu–B3Πg). In this work, the neutral temperature was estimated using this technique for flowing discharges of argon, helium, neon, nitrogen, and oxygen as a function of pressure and power. It was found that the neutral temperature for all of the discharges studied increased roughly proportional to the logarithm of the pressure. An increase in neutral temperature was also observed with increases in power; however, the dependence did not follow a simple functional form. The rare gases exhibited temperatures significantly above room temperature under high power (1200 W) and high pressure (∼1 Torr) conditions with argon approaching 2000 K. Molecular discharges such as N2 and O2 exhibited significantly higher temperatures (approaching 2500 K) than the rare gases even though they are expected to have lower plasma densities at the same pressure and power. It is believed that Franck–Condon heating of the gases during electron impact dissociation, vibrational excitation/thermalization, and exothermic wall reactions may all play important roles in producing such elevated temperatures. Simple, zero-dimensional plasma modeling indicates that neutral temperature elevation will result in significant increases in discharge electron temperature and electron-impact reaction rate coefficients under the same operating conditions.
Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase
Authors: Munn David H. , Sharma Madhav D. , Lee Jeffrey R. , Jhaver Kanchan G. , Johnson Theodore S. , Keskin Derin B. , Marshall Brendan , Chandler Phillip , Antonia Scott J. , Burgess Russell , Slingluff Craig L. , Mellor Andrew L.
Published: September 2002

Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive APCs constituted a discrete subset identified by coexpression of the cell-surface markers CD123 and CCR6. In the dendritic cell (DC) lineage, IDO-mediated suppressor activity was present in fully mature as well as immature CD123
+
DCs. IDO
+
DCs could also be readily detected in vivo, which suggests that these cells may represent a regulatory subset of APCs in humans.
Instruction of Translating Ribosome by Nascent Peptide
Authors: Gong Feng , Yanofsky Charles
Published: September 2002

Expression of the tryptophanase operon of
Escherichia coli
is regulated by catabolite repression and tryptophan-induced transcription antitermination. An induction site activated by
l
-tryptophan is created in the translating ribosome during synthesis of TnaC, the 24-residue leader peptide. Replacing the
tnaC
stop codon with a tryptophan codon allows tryptophan-charged tryptophan transfer RNA to substitute for tryptophan as inducer. This suggests that the ribosomal A site occupied by the tryptophanyl moiety of the charged transfer RNA is the site of induction. The location of tryptophan-12 of nascent TnaC in the peptide exit tunnel was crucial for induction. These results show that a nascent peptide sequence can influence translation continuation and termination within a translating ribosome.
Chromatin Higher Order Folding--Wrapping up Transcription
Authors: Horn Peter J. , Peterson Craig L.
Published: September 2002

Eukaryotic genomes are organized into condensed, heterogeneous chromatin fibers throughout much of the cell cycle. Here we describe recent studies indicating that even transcriptionally active loci may be encompassed within 80- to 100-nanometer-thick chromonema fibers. These studies suggest that chromatin higher order folding may be a key feature of eukaryotic transcriptional control. We also discuss evidence suggesting that adenosine-5′-triphosphate–dependent chromatin-remodeling enzymes and histone-modifying enzymes may regulate transcription by controlling the extent and dynamics of chromatin higher order folding.
Relative Timing of Deglacial Climate Events in Antarctica and Greenland
Authors: Morgan Vin , Delmotte Marc , van Ommen Tas , Jouzel Jean , Chappellaz Jérôme , Woon Suenor , Masson-Delmotte Valérie , Raynaud Dominique
Published: September 2002

The last deglaciation was marked by large, hemispheric, millennial-scale climate variations: the Bølling-Allerød and Younger Dryas periods in the north, and the Antarctic Cold Reversal in the south. A chronology from the high-accumulation Law Dome East Antarctic ice core constrains the relative timing of these two events and provides strong evidence that the cooling at the start of the Antarctic Cold Reversal did not follow the abrupt warming during the northern Bølling transition around 14,500 years ago. This result suggests that southern changes are not a direct response to abrupt changes in North Atlantic thermohaline circulation, as is assumed in the conventional picture of a hemispheric temperature seesaw.
Observation of a Membrane Fusion Intermediate Structure
Authors: Yang Lin , Huang Huey W.
Published: September 2002

We report the observation of a phase of phospholipid that contains a structure similar to the commonly postulated interbilayer state that is crucial to membrane fusion. The widely accepted model for membrane fusion suggests that there is an intermediate state in which the two contacting monolayers become continuous via an hourglass-shaped structure called a stalk. Many efforts have been made to estimate the free energy for such a state in order to understand the functionality of membrane fusion proteins and to define key parameters in energy estimates. The observation of the stalk structure supports the stalk hypothesis for membrane fusion and enables the measurement of these parameters experimentally.
Deformation on Nearby Faults Induced by the 1999 Hector Mine Earthquake
Authors: Fialko Yuri , Sandwell David , Agnew Duncan , Simons Mark , Shearer Peter , Minster Bernard
Published: September 2002

Interferometric Synthetic Aperture Radar observations of surface deformation due to the 1999 Hector Mine earthquake reveal motion on several nearby faults of the eastern California shear zone. We document both vertical and horizontal displacements of several millimeters to several centimeters across kilometer-wide zones centered on pre-existing faults. Portions of some faults experienced retrograde (that is, opposite to their long-term geologic slip) motion during or shortly after the earthquake. The observed deformation likely represents elastic response of compliant fault zones to the permanent co-seismic stress changes. The induced fault displacements imply decreases in the effective shear modulus within the kilometer-wide fault zones, indicating that the latter are mechanically distinct from the ambient crustal rocks.
Dependence of Heterochromatic Histone H3 Methylation Patterns on the
Arabidopsis
Gene
DDM1
Authors: Gendrel Anne-Valérie , Lippman Zachary , Yordan Cristy , Colot Vincent , Martienssen Robert A.
Published: September 2002

The
Arabidopsis
gene
DDM1
is required to maintain DNA methylation levels and is responsible for transposon and transgene silencing. However, rather than encoding a DNA methyltransferase,
DDM1
has similarity to the SWI/SNF family of adenosine triphosphate–dependent chromatin remodeling genes, suggesting an indirect role in DNA methylation. Here we show that
DDM1
is also required to maintain histone H3 methylation patterns. In wild-type heterochromatin, transposons and silent genes are associated with histone H3 methylated at lysine 9, whereas known genes are preferentially associated with methylated lysine 4. In
ddm1
heterochromatin, DNA methylation is lost, and methylation of lysine 9 is largely replaced by methylation of lysine 4. Because DNA methylation has recently been shown to depend on histone H3 lysine 9 methylation, our results suggest that transposon methylation may be guided by histone H3 methylation in plant genomes. This would account for the epigenetic inheritance of hypomethylated DNA once histone H3 methylation patterns are altered.
A Photoactivatable GFP for Selective Photolabeling of Proteins and Cells
Authors: Patterson George H. , Lippincott-Schwartz Jennifer
Published: September 2002

We report a photoactivatable variant of the
Aequorea victoria
green fluorescent protein (GFP) that, after intense irradiation with 413-nanometer light, increases fluorescence 100 times when excited by 488-nanometer light and remains stable for days under aerobic conditions. These characteristics offer a new tool for exploring intracellular protein dynamics by tracking photoactivated molecules that are the only visible GFPs in the cell. Here, we use the photoactivatable GFP both as a free protein to measure protein diffusion across the nuclear envelope and as a chimera with a lysosomal membrane protein to demonstrate rapid interlysosomal membrane exchange.
A Proton Buffering Role for Silica in Diatoms
Authors: Milligan Allen J. , Morel François M. M.
Published: September 2002

For 40 million years, diatoms have dominated the reverse weathering of silica on Earth. These photosynthetic protists take up dissolved silicic acid from the water and precipitate opaline silica to form their cell wall. We show that the biosilica of diatoms is an effective pH buffer, enabling the enzymatic conversion of bicarbonate to CO
2
, an important step in inorganic carbon acquisition by these organisms. Because diatoms are responsible for one-quarter of global primary production and for a large fraction of the carbon exported to the deep sea, the global cycles of Si and C may be linked mechanistically.
Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi
Authors: Volpe Thomas A. , Kidner Catherine , Hall Ira M. , Teng Grace , Grewal Shiv I. S. , Martienssen Robert A.
Published: September 2002

Eukaryotic heterochromatin is characterized by a high density of repeats and transposons, as well as by modified histones, and influences both gene expression and chromosome segregation. In the fission yeast
Schizosaccharomyces pombe
, we deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference (RNAi). Deletion results in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats. This is accompanied by transcriptional de-repression of transgenes integrated at the centromere, loss of histone H3 lysine-9 methylation, and impairment of centromere function. We propose that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi.
What Is an Explanation?
Authors: Slack Jonathan
Published: September 2002

Making Sense of Life
Explaining Biological Development with Models, Metaphors, and Machines. Evelyn Fox Keller. Harvard University Press, Cambridge, MA, 2002. 400 pp. $29.95, £20.50, $29.95. ISBN 0-674-00746-8.

Motivated by the philosophical problem of what it means to understand organismal development, Keller offers a selective history of developmental biology with a focus on the contributions of mathematical and theoretical approaches.
Water Diffusion and Clustering on Pd(111)
Authors: Mitsui T. , Rose M. K. , Fomin E. , Ogletree D. F. , Salmeron M.
Published: September 2002

The adsorption, diffusion, and clustering of water molecules on a Pd(111) surface were studied by scanning tunneling microscopy. At 40 kelvin, low-coverage water adsorbs in the form of isolated molecules, which diffuse by hopping to nearest neighbor sites. Upon collision, they form first dimers, then trimers, tetramers, and so on. The mobility of these species increased by several orders of magnitude when dimers, trimers, and tetramers formed, and decreased again when the cluster contained five or more molecules. Cyclic hexamers were found to be particularly stable. They grow with further exposure to form a commensurate hexagonal honeycomb structure relative to the Pd(111) substrate. These observations illustrate the change in relative strength between intermolecular hydrogen bonds and molecule-substrate bonds as a function of water cluster size, the key property that determines the wetting properties of materials.
Development of One-Dimensional Band Structure in Artificial Gold Chains
Authors: Nilius N. , Wallis T. M. , Ho W.
Published: September 2002

The ability of a scanning tunneling microscope to manipulate single atoms is used to build well-defined gold chains on NiAl(110). The electronic properties of the one-dimensional chains are dominated by an unoccupied electron band, gradually developing from a single atomic orbital present in a gold atom. Spatially resolved conductance measurements along a 20-atom chain provide the dispersion relation, effective mass, and density of states of the free electron–like band. These experiments demonstrate a strategy for probing the interrelation between geometric structure, elemental composition, and electronic properties in metallic nanostructures.
A Major Archean, Gold- and Crust-Forming Event in the Kaapvaal Craton, South Africa
Authors: Kirk Jason , Ruiz Joaquin , Chesley John , Walshe John , England Gavin
Published: September 2002

The 2.89- to 2.76-gigayear-old conglomerates of the Central Rand Group of South Africa host an immense concentration of gold. The gold and rounded pyrites from the conglomerates yield a rhenium-osmium isochron age of 3.03 ± 0.02 gigayears and an initial
187
Os/
188
Os ratio of 0.1079 ± 0.0001. This age is older than that of the conglomerates. Thus, the gold is detrital and was not deposited by later hydrothermal fluids. This Middle Archean gold mineralization event corresponds to a period of rapid crustal growth in which much of the Kaapvaal craton was formed and is evidence for a significant noble metal flux from the mantle.
Origin
Was Just a Beginning
Authors: Larson Edward J.
Published: September 2002

Charles Darwin
The Power of Place. Volume 2 of a Biography. Janet Browne. Knopf, New York, 2002. 624 pp. $37.50, C$56.50. ISBN 0-679-42932-8. To be published 14 November by Cape, London. £25. ISBN 0-224-04212-2.

Browne concludes her two-volume biography with a comprehensive account of the details and context of Darwin's activities between the 1858 arrival of Wallace's letter from the East Indies and her subject's death in 1882.
BRCA2 Function in DNA Binding and Recombination from a BRCA2-DSS1-ssDNA Structure
Authors: Yang Haijuan , Jeffrey Philip D. , Miller Julie , Kinnucan Elspeth , Sun Yutong , Thomä Nicolas H. , Zheng Ning , Chen Phang-Lang , Lee Wen-Hwa , Pavletich Nikola P.
Published: September 2002

Mutations in the
BRCA2
(breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a ∼90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)
9
, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.
Functional Blocking of
Staphylococcus aureus
Adhesins following Growth in Ex Vivo Media
Authors: Massey Ruth C. , Dissanayeke Shobana R. , Cameron Brian , Ferguson David , Foster Timothy J. , Peacock Sharon J.
Published: September 2002

Defining the role of
Staphylococcus aureus
adhesins in disease pathogenesis may depend on the use of bacteria grown in culture media that more closely reflect the human milieu than conventional broth. This study examined the functional effect on
S. aureus
adhesins following growth in an ex vivo medium containing a complex mixture of human proteins (used peritoneal dialysate) relative to growth in Todd-Hewitt broth. The adherence of
S. aureus
, cultured in dialysate, to fibronectin and fibrinogen was markedly reduced despite the expresion of full-length ClfA, ClfB, and fibronectin-binding proteins. Growth in dialysate resulted in the acquisition of a surface coat, as visualized by transmission electron microscopy, which was shown to contain fibronectin, fibrinogen, and immunoglobulins. Adherence of
S. aureus
to fibrinogen following growth in dialysate was significantly reduced by expression of protein A but was restored following growth in immunoglobulin-depleted dialysate. We conclude that bacterial adherence to solid-phase protein is critically dependent on the culture medium, that
S. aureus
adhesins may become saturated with target protein prior to contact with solid surfaces, and that there is an interaction between fibrinogen-binding proteins and immunoglobulin bound to protein A following contact with host proteins. These findings have important implications for future studies of
S. aureus
adhesins.
The Class A Macrophage Scavenger Receptor Is a Major Pattern Recognition Receptor for
Neisseria meningitidis
Which Is Independent of Lipopolysaccharide and Not Required for Secretory Responses
Authors: Peiser Leanne , de Winther Menno P. J. , Makepeace Katherine , Hollinshead Michael , Coull Philip , Plested Joyce , Kodama Tatsuhiko , Moxon E. Richard , Gordon Siamon
Published: September 2002

Macrophages (Mφ) play a key role in the pathogenesis of invasive meningococcal infections. The roles of two pattern recognition molecules, the Mφ scavenger receptor (SR-A) and Toll-like receptor 4 (TLR-4), have been investigated using bone marrow culture-derived Mφ (BMMφ). Surprisingly, a comparison of BMMφ from wild-type and SR-A knockout (SR-A
−/−
) mice showed that nonopsonic phagocytosis of meningococci was mediated almost exclusively via SR-A. Previous studies have demonstrated only a partial involvement of the receptor in the uptake of other bacteria, such as
Escherichia coli
. Interestingly, we also show that lipopolysaccharide (LPS) was not the ligand for the receptor on these organisms. Further study of the downstream events of SR-A-mediated ingestion of
Neisseria meningitidis
demonstrated that SR-A was not required for cytokine production. To determine the bacterial and host factors required to stimulate Mφ activation, we examined TLR-4-deficient Mφ from C3H/HeJ mice and LPS-deficient meningococci. TLR-4-deficient cells elaborated reduced amounts of tumor necrosis factor alpha, interleukin-12 (IL-12), and IL-10, even though ingestion via SR-A was unaffected in these cells. Similarly, although there was no change in SR-A-mediated ingestion of LPS-deficient meningococci, the mutant failed to stimulate a Mφ-dependent cytokine response. Thus, we show that Mφ SR-A mediates opsonin-independent uptake of
N. meningitidis
independently of lipid A and that this activity is uncoupled from the Mφ secretion of proinflammatory cytokines, which provides a basis for further investigation of the role of this receptor in meningococcal disease in humans.
The Alternative Sigma Factor σ
E
Plays an Important Role in Intestinal Survival and Virulence in
Vibrio cholerae
Authors: Kovacikova Gabriela , Skorupski Karen
Published: September 2002

The alternative sigma factor σ
Ε
(RpoE) is involved in the response to extracytoplasmic stress and plays a role in the virulence of a variety of different bacteria. To assess the role of σ
Ε
in
Vibrio cholerae
pathogenesis, a
ΔrpoE
mutant was constructed and analyzed using the infant mouse model. The results here show that σ
Ε
contributes significantly to the virulence of
V. cholerae
. The Δ
rpoE
mutant was highly attenuated with a 50% lethal dose more than 3 logs higher than that for the parental strain, and its ability to colonize the intestine was reduced approximately 30-fold. A time course of infection revealed that the number of CFU of the Δ
rpoE
mutant was approximately 1 log lower than that of the parental strain by 12 h postinoculation and decreased further by 24 h. The defect in virulence in the Δ
rpoE
mutant thus appears to be a diminished ability to survive within the intestinal environment. The results here also show that σ
Ε
is not required for growth and survival of
V. cholerae
in vitro at high temperatures but is required under other stressful conditions, such as in the presence of 3% ethanol. As in
Escherichia coli
, the expression of
rpoE
in
V. cholerae
is dependent upon two promoters located upstream of the gene, P1 and P2. P1 appears to be σ
70
dependent, whereas the downstream promoter, P2, is positively autoregulated by σ
Ε
.
Immune Responses to Novel Pneumococcal Proteins Pneumolysin, PspA, PsaA, and CbpA in Adenoidal B Cells from Children
Authors: Zhang Qibo , Choo Sharon , Finn Adam
Published: September 2002

Studies of mice suggest that pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, are promising vaccine candidates. To determine whether these proteins are good mucosal immunogens in humans, adenoidal lymphocytes from 20 children who had adenoidectomies were isolated and tested by ELISpot for antigen-specific antibody-secreting cells (ASCs). Cells were also cultured for 7 days in the presence of a concentrated culture supernatant (CCS) from a type 14 strain of pneumococcus which contained secreted pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, and then tested by ELISpot. ELISpot assays done on freshly isolated cells detected ASCs to all four antigens in most children studied. However, there were differences both between antigens and between isotypes. The densities of immunoglobulin G (IgG) ASCs against both PsaA and CbpA were significantly higher than those of ASCs for PspA and PdB (pneumolysin toxoid B) (
P
< 0.001). For all antigens, the numbers of IgA ASCs tended to be lower than those of both IgG and IgM ASCs. The numbers of anti-CbpA and -PsaA IgA ASCs were higher than those of anti-PdB IgA ASCs (
P
< 0.01). Concentrations of IgA antibodies to PspA and PsaA in saliva correlated with the numbers of IgA ASCs to PspA and PsaA in freshly isolated adenoidal cells, but no such correlation was found between salivary IgG antibody concentrations and IgG ASCs to the four antigens in adenoidal cells. In cultured cells, anti-PspA, -PsaA, and -CbpA IgG ASCs proliferated significantly, but only two of eight samples showed >2-fold increases in anti-CbpA and -PspA IgA ASCs after CCS stimulation. The results suggest that CbpA, PsaA, and PspA may be good upper respiratory mucosal antigens in children. Adenoids may be important inductive sites for memory IgG responses and important sources of salivary IgA. Some protein antigens may also prime for mucosal IgA memory. These data support the effort to explore mucosal immunization against pneumococcal infection.
Essential Role for Verotoxin in Sustained Stress-Activated Protein Kinase and Nuclear Factor Kappa B Signaling, Stimulated by
Escherichia coli
O157:H7 in Vero Cells
Authors: Cameron Pamela , Bingham Deborah , Paul Andrew , Pavelka Martin , Cameron Scott , Rotondo Dino , Plevin Robin
Published: September 2002

The effects of
Escherichia coli
O157:H7 (strains E30480 and PM601) and the associated verotoxins (VTs), VT1 and VT2, on stress-activated protein kinase and nuclear factor kappa B (NF-κB) signaling were investigated with Vero cells, which are extremely sensitive to the cytotoxic effects of
E. coli
O157:H7 in vitro. Cell-free supernatants prepared from E30480 and PM601 cultures and purified VT1 and VT2 stimulated a strong and prolonged (>4-h) activation of both c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. However, JNK activity stimulated in response to E30480 supernatants was substantially reduced following pretreatment with anti-VT1 and anti-VT2 antibodies, while a VT1 and VT2 gene knockout mutant of PM601 was unable to stimulate JNK activity. E30480 supernatants also caused a sustained activation of NF-κB DNA binding, degradation of inhibitory kappa B alpha (IκBα), and an increase in inhibitory kappa B kinase α activity, although PM601 supernatants and VT1 and VT2 had no effect. However, preincubation with VTs prolonged the transient activation of NF-κB and IκBα degradation stimulated by either tumor necrosis factor alpha or interleukin 1β, while preincubation with anti-VT antibodies prevented the prolonged loss of IκBα and partially reduced DNA binding in response to E30480 supernatants. These results strongly suggest that in Vero cells, VT plays an essential role in sustained JNK and NF-κB signaling in response to
E. coli
O157:H7 and that this action may underpin their cell-selective cytotoxic effects. These studies also suggest that another component released by strain E30480 contributes to the early activation of JNK and NF-κB.
Contribution of Membrane-Damaging Toxins to
Bacillus
Endophthalmitis Pathogenesis
Authors: Callegan Michelle C. , Cochran Daniel C. , Kane Scott T. , Gilmore Michael S. , Gominet Myriam , Lereclus Didier
Published: September 2002

Membrane-damaging toxins are thought to be responsible for the explosive clinical course of
Bacillus
endophthalmitis. This study analyzed the contribution of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific phospholipase C (PC-PLC) to the pathogenesis of experimental
Bacillus
endophthalmitis. Isogenic mutants were constructed by insertion of
lacZ
into
Bacillus thuringiensis
genes encoding PI-PLC (
plcA
) and PC-PLC (
plcB
). Rabbit eyes were injected intravitreally with 2 log
10
CFU of strain BT407 (wild type), the PI-PLC mutant (BT
plcA
::
lacZ
), or the PC-PLC mutant (BT
plcB
::
lacZ
). The rates of decrease in retinal responses of eyes infected with the isogenic mutants were similar to that of wild type, with all infections resulting in elimination of retinal function by 18 h. Strain BT407 caused a significant increase in the latency of retinal responses at 6 h, but strains BT
plcA
::
lacZ
and BT
plcB
::
lacZ
did not. All strains elicited significant inflammatory cell influx into the anterior chamber by 12 h. Histologically, eyes infected with each strain were indistinguishable throughout the infection course. In this model, neither PI-PLC nor PC-PLC had an effect on the course or severity of experimental
Bacillus
endophthalmitis. Alterations in retinal responses early in infection may mark the beginnings of specific photoreceptor or glial cell dysfunction.
BhuR, a Virulence-Associated Outer Membrane Protein of
Bordetella avium
, Is Required for the Acquisition of Iron from Heme and Hemoproteins
Authors: Murphy Erin R. , Sacco Randy E. , Dickenson Amy , Metzger Daniel J. , Hu Yan , Orndorff Paul E. , Connell Terry D.
Published: September 2002

Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe. The gram-negative bacterium
Bordetella avium
, upon colonization of the avian upper respiratory tract, produces a disease in birds that has striking similarity to whooping cough, a disease caused by the obligate human pathogen
Bordetella pertussis
. We describe a
B. avium
Fe utilization locus comprised of
bhuR
and six accessory genes (
rhuIR
and
bhuSTUV
). Genetic manipulations of
B. avium
confirmed that
bhuR
, which encodes a putative outer membrane heme receptor, mediates efficient acquisition of Fe from hemin and hemoproteins (hemoglobin, myoglobin, and catalase). BhuR contains motifs which are common to bacterial heme receptors, including a consensus FRAP domain, an NPNL domain, and two TonB boxes. An N-terminal 32-amino-acid segment, putatively required for
rhuIR
-dependent regulated expression of
bhuR
, is present in BhuR but not in other bacterial heme receptors. Two forms of BhuR were observed in the outer membrane of
B. avium
: a 91-kDa polypeptide consistent in size with the predicted mature protein and a smaller 82-kDa polypeptide which lacks the 104 amino acids found at the N terminus of the 91-kDa form. A mutation in
hemA
was engineered in
B. avium
to demonstrate that the bacterium transports heme into the cytoplasm in a BhuR-dependent manner. The role of BhuR in virulence was established in turkey poults by use of a competitive-infection model.
Characterization of a Novel Intracellularly Activated Gene from
Salmonella enterica
Serovar Typhi
Authors: Basso Holger , Rharbaoui Faiza , Staendner Lothar H. , Medina Eva , García-Del Portillo Francisco , Guzmán Carlos A.
Published: September 2002

A
Salmonella enterica
serovar Typhi gene that is selectively up-regulated upon bacterial invasion of eukaryotic cells was characterized. The open reading frame encodes a 298-amino-acid hydrophobic polypeptide (30.8 kDa), which is predicted to be an integral membrane protein with nine membrane-spanning domains. The protein is closely related (87 to 94% reliability) to different transport and permease systems. Gene expression under laboratory conditions was relatively weak; however, sevenfold induction was observed in a high-osmolarity medium (300 mM NaCl). The growth pattern in a laboratory medium of a serovar Typhi strain Ty2 derivative containing a 735-bp in-frame deletion in this gene, named
gaiA
(for gene activated intracellularly), was not affected. In contrast, the mutant was partially impaired in intracellular survival in murine peritoneal macrophages, as well as in human monocyte-derived macrophages. However, in the case of human macrophages, this survival defect was modest and evident only at late infection times (24 h). Despite the distinct intracellular survival kinetics displayed in macrophages of different species, the
gaiA
null mutant was significantly affected in its potential to trigger apoptosis in both murine and human macrophages. Provision of the
gaiA
gene in
trans
resulted in complementation of these phenotypes. Interestingly, the absence of a functional
gaiA
gene caused a marked attenuation in the mouse mucin model, as shown by the increase (3 orders of magnitude) in the 50% lethal dose of the mutant strain over that of the parental strain Ty2 (
P
≤ 0.05). Altogether, these data indicate that the product encoded by the
gaiA
gene is required for triggering apoptosis and bacterial survival within murine macrophages, which is consistent with the in vivo results obtained in the mouse mucin model. However,
gaiA
was not required for initial intracellular survival in human cells, indicating that its role in the natural host might be more complex than is suggested by the studies performed in the murine system.