bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomic step organization in homoepitaxial growth on GaAs(111)B substrates
Authors: Schowalter Leo J. , Yang Kai , Thundat Thomas
Published: July 2002

When homoepitaxial growth is performed on exactly oriented (singular) (1̄1̄1̄) GaAs substrates, while maintaining the √19×√19 surface reconstruction, the originally flat surface spontaneously evolves vicinal (1̄1̄1̄) facets that are tilted approximately 2.5° toward the 〈21̄1̄〉 azimuthal directions. These facets form pyramidlike structures where the distance between adjacent peaks can be varied from as little as 1μm to 10’s of μm. When these surfaces are observed with atomic force microscopy (AFM), we find that they are extremely smooth with the observed tilt resulting from atomic steps which are spaced at approximately 7.5 nm. We have also studied growth on vicinal GaAs(1̄1̄1̄) substrates. If the substrate surfaces are tilted 3° toward the [21̄1̄] direction, then a very smooth surface is obtained with a rather uniform spacing of atomic steps running along the [01̄1̄] direction. For vicinal substrates that are tilted 2° or less toward the [21̄1̄] azimuth, the surface evolves a grating structure consisting of approximately singular (1̄1̄1̄) facets and vicinal (1̄1̄1̄) facets that are tilted approximately 2.5° toward the [21̄1̄] azimuth. As the sizes of the singular (1̄1̄1̄) facets are made larger (by growing on vicinal substrates with smaller misorientations), occasional inclined three-sided pyramids are observed with the three symmetric, vicinal (1̄1̄1̄) facets. Vicinal substrates that are tilted along other directions are observed to form zigzag terraces that result from appropriate combinations of oriented and vicinal (1̄1̄1̄) facets. Our results are interpreted as indicating that the 2.5° vicinal (1̄1̄1̄) surface has a minimum free energy for the √19×√19 reconstruction (i.e., that 10 nm spacing of 〈011〉 steps is thermodynamically preferred). Exactly oriented (1̄1̄1̄) facets are only observed when their facet width is less than a couple of micrometers implying a minimum nucleation size. This is a very surprising result since conventional wisdom argues the surfaces with low Miller indexes are preferred. This tendency to form step bunches could be utilized to better control the growth of quantum wires and quantum dots.
Calculation of the average interface field in inversion layers using zero-temperature Green’s function formalism
Authors: Vasileska Dragica , Bordone Paolo , Eldridge Terry , Ferry David K.
Published: July 2002

We investigate the dependence of the average interface field on the inversion and depletion charge density through the use of a zero-temperature Green’s function formalism for the evaluation of the broadening of the electronic states and conductivity. Various models for the surface-roughness autocovariance function existing in the literature, including both Gaussian and exponential models, are studied in our calculations. Besides surface-roughness scattering, the dominant scattering mechanism at high electron densities, charged impurity, interface-trap and oxide charge scattering are also included. The position of the subband minima, as well as the electron wave functions, are obtained by a self-consistent solution of the Schrödinger, Poisson, and Dyson equations for each value of the inversion charge density. Many-body effects are included by considering the screened matrix elements for the scattering mechanisms and through inclusion of the exchange-correlation term. The dependence of the mobility and the effective field upon the inversion charge density is sensitive to the model chosen, and we discuss the manner in which this may be used to study the interface itself.
Modeling and design of space charge lenses/aberration correctors for focused ion beam systems
Authors: Tang Tiantong , Orloff Jon , Wang Li
Published: July 2002

Spherical and chromatic aberrations of electrostatic lenses with negative space charge in axial area are studied. A ‘‘toroidal subbeam’’ algorithm has been developed to model the evolution of the current and charge density distributions of intense charged particle beams taking into account space charge and initial thermal velocity effects. Optimized designs are presented which prove that negative spherical and chromatic aberration coefficients can be achieved for a space charge lens using an electron gun to produce the space charge cloud.
Application of optical lithography for high aspect ratio microstructures
Authors: Loechel B. , Demmeler R. , Rothe M. , Bruenger W. , Fehlberg S. , Gruetzner G.
Published: July 2002

Interest in thick photoresist applications is steadily growing. Besides the bump fabrication and wire interconnect technology, the process of patterning thick layer photoresists by UV lithography is specially qualified for applications in micro electro mechanical systems. Specialized equipment and new photoresists have been developed or are under development to cope with the new challenges in the field of preparing extremely thick photoresist layers, to plan the process of patterning these thick resists, and to deal with the difficulties of the following galvanoplating step. A technology called three-dimensional (3D) UV-microforming was developed, consisting of a resist preparation process for very thick photoresists (positive or negative tone), UV lithographic steps, resist development, moulding procedures by galvanodeposition, and finally stripping and cleaning for finishing the structures. A minimum width of 3 μm for the resist bars was found to be necessary to withstand the fabrication process of lines and spaces in 15 μm thick resist. For thicker layers high aspect ratios of more than 10 as well as steep edges of more than 88° could be fabricated. The resist patterns were moulded by using electroplating. For microsystem applications metals and alloys can be deposited into the resist patterns. 3D UV-microforming, a combination of UV patterning of thick layer resists and galvanoplating, enables the low-cost fabrication of a wide variety of micro components for many different users.
Ultralow voltage imaging
Authors: Hordon L. S. , Monahan K. M.
Published: July 2002

Low-voltage (<1 kV) electron beams have become widely used in the semiconductor industry for nondestructive imaging of integrated circuits. By focusing the electron beam onto the device at an energy close to EII, the unity-yield point of the material, charging can be minimized. In addition, the penetration depth of the beam into the device is greatly reduced, generating images which carry more surface information and minimizing beam-induced damage. In this paper we discuss electron beam imaging at ultralow voltages (100–800 V). Within this range, the landing energy is optimal for many insulating materials used in semiconductor devices. Resolution better than or equal to 5 nm is attainable at 600 eV landing energy, and the weak dependence of resolution on landing energy allows the selection of an appropriate energy for a particular material or contrast mechanism.
Design and performance analysis of a three-dimensional sample translation device used in ultrahigh vacuum scanned probe microscopy
Authors: Schlittler R. R. , Gimzewski J. K.
Published: July 2002

For micropatterned or technological samples and to achieve overlap with lower magnification microscopic techniques, there is a demand for high-resolution imaging capabilities in combination with reproducible sample translation. Degradation of the signal-to-noise ratio and piezo nonlinearities limit the maximum scan range, resolution and, in particular, the linearity of piezo scanners. To overcome these problems, we have designed and operated a compact three-dimensional inertially driven translation device for scanning probe microscopy techniques. We demonstrate the operation of the device, which can access a volume of 2 cm3 in three-dimensional space and permits imaging with atomic resolution. Reproducibility of step size is analyzed in detail. The importance of selected material pairing of the sliding components is discussed for ultrahigh vacuum operation.
An inquiry concerning the principles of Si 2p core-level photoemission shift assignments at the Si/SiO2 interface
Authors: McFeely F. R. , Zhang K. Z. , Banaszak Holl Mark M. , Lee Sunghee , Bender John E.
Published: July 2002

It has long been held that high resolution x-ray photoemission spectra of the Si 2p core level at SiSiO2 interfaces provide important structural information, and that any credible interfacial model must be able to account for these data. To this end it has traditionally been assumed that there existed a one-to-one relationship between chemically shifted spectral features and interfacial silicon atoms in specific formal oxidation states. A series of new measurements of Si 2p core level binding energies for cluster-derived Si/Si oxide interfaces appear to stand in direct contradiction to this critical assumption. In this article we present a critique of various responses to the challenge posed by the new observations. Particular attention is given to the logical consequences of either maintaining or rejecting the one-to-one relationship between shifted features and formal silicon oxidation states and to the challenges each of these responses must meet if they are to prevail.
Experiments of highly emissive metal–oxide–semiconductor electron tunneling cathode
Authors: Yokoo Kuniyoshi , Koshita Gen , Hanzawa Satoru , Abe Yoshiaki , Neo Yoichiro
Published: July 2002

An effective mean-free path of hot electrons in the conduction band of SiO2 in a Si-gate metal–oxide–semiconductor (MOS) electron tunneling cathode was measured and found to be about 0.7 nm. Following these observations, we proposed and fabricated a depletion gate MOS electron tunneling cathode. The highest transfer ratio of 13.3% was achieved in the cathode at the low emission current level, which was considerably higher than that of tunneling cathodes studied in the past. However, the ratio decreased drastically at high current due to the hole injection into the depletion region from the gate.
Atomic force microscope study of chromatic transitions in polydiacetylene thin films
Authors: Lio A. , Reichert A. , Nagy J. O. , Salmeron M. , Charych D. H.
Published: July 2002

Despite decades of study, the exact mechanism for chromatic transitions in polydiacetylene materials remains somewhat elusive. The mechanism of the blue to red color transition for overcompressed mixed lipid thin films of 10,12 pentacosadiynoic acid has been investigated by atomic force microscopy. Blue layers were prepared by the horizontal Langmuir–Schaefer deposition method. The red form was attained by thermal annealing of blue films (thermochromism). The blue films reveal micro-sized domains. Each domain shows a stripelike morphology on top of a nearly complete layer. The polymer backbone direction shows a high degree of order. A partial disorder is shown to exist along the interbackbone direction. Our study of the red form films indicates that changes occur in the micron-scale morphology of the films. Interestingly the alkyl side chains rearrange into a completely ordered structure and remain ordered well beyond the transition temperature (70 °C<T<90 °C). Our results strongly suggest that the reorganization of the side chains is the origin of the thermochromic effect for these films.
Deconvolution of tip affected atomic force microscope images and comparison to Rutherford backscattering spectrometry
Authors: Tabet M. F. , Urban F. K.
Published: July 2002

There is distortion in atomic force microscope (AFM) images caused by a nonideal shape and size of the probe tip. This is called tip effect and is due to the convolution of the tip and sample. AFM images of nanometer size islands of zinc deposited on silicon substrates by the ionized cluster beam deposition technique were used to investigate this effect. The number of zinc atoms per unit area determined by each of two methods, the AFM images and Rutherford backscattering spectrometry (RBS) are compared and the AFM reported more zinc than RBS. A partial explanation for this difference is that the convolution of the tip and sample makes the islands appear larger in the AFM data. Previously reported convolution and deconvolution algorithms were implemented to study and simulate the interaction between tip and sample in the AFM. The deconvolution algorithm removes part of the distortion by taking into account the physical volume occupied by the tip which exposes a more accurate image. After deconvolution of the zinc islands images there was better agreement between AFM and RBS results. Deconvolution of other images will also be discussed.
Theory of interfaces and surfaces in wide-gap nitrides
Authors: Nardelli Marco Buongiorno , Rapcewicz Krzysztof , Bernholc J.
Published: July 2002

A selection of the results of a theoretical investigation of the properties of interfaces and surfaces of the wide-gap III–V nitride semiconductors is reviewed. The electronic properties of wurtzite heteroepitaxial interfaces of AlN and GaN, incorporating the effects of strain, are discussed. In particular, we find that this interface is of type I and have calculated the valence-band offset to be −0.57 eV. The surface energies and atomic geometries of the 2×2 reconstructions of the (0001) face of GaN are also presented. In conditions which are rich in a given species, an adatom reconstruction of that species is found to be the most energetically favorable: for gallium-rich conditions, the reconstruction with a gallium adatom on a T3 site is the most stable, while for nitrogen-rich conditions the reconstruction with a nitrogen adatom on the H3 site is energetically the most favorable.
Negative differential resistance on single electron transport in a junction array of ultrasmall islands
Authors: Nakashima Hiroshi , Uozumi Kiyohiko
Published: July 2002

We predict a new type of negative differential resistance (NDR) in a nonlinear ten-junction array of nine conducting islands with ultrasmall self-capacitance. A main feature of our array is that two of the ten junctions go in the direction opposite to an external in-plane electric field. The NDR characteristic is one of Coulomb blockade phenomena and is triggered by competition between the two tunnel rates across two specific junctions depending on the external voltage. Calculations for the electron dynamics are based on the orthodox semiclassical single electron tunneling model.
Bias-temperature stability of the Cu(Mg)/SiO2/p-Si metal-oxide-semiconductor capacitors
Authors: de Felipe T. Suwwan , Murarka S. P. , Bedell S. , Lanford W. A.
Published: July 2002

This work studies the consequences of alloying copper with 2 at % magnesium on the transport of copper through the SiO2 dielectric when subjected to bias temperature aging (BTA). Metal-oxide semiconductor structures, that were thermally annealed at different temperature, were BTA under an electric field of 2.35 MV/cm at varying temperatures and for varying periods of time. The resulting capacitance–voltage (C–V) and I–V curves indicate that the samples thermally annealed above 300 °C form a passivating film between the oxide-metal interface and the metal surface. This oxide film is assumed to cause an inhibition of the diffusion or drifting of copper into the SiO2 and is responsible for the observed stability in the C–V and I–V curves.
Efficient diffractive optics made by single-step electron beam lithography in solid PMMA
Authors: Cumming David R. S. , Khandaker Iman I. , Thoms Stephen , Casey Brendan G.
Published: July 2002

Diffractive optics are of increasing interest as they can be used to make compact optical components of great complexity. However, they require precision of fabrication on a scale significantly below the operating wavelength in order to achieve high efficiency. We describe a new technique for making multilevel diffractive optics in a single step by the patterning of solid poly methyl methacrylate (PMMA) as opposed to conventional thin films. We have characterized the process to optimize it for development, dose, and beam current. Using the technique we have made blazed diffraction gratings for use in transmission or reflection with efficiencies as high as 83% at a wavelength of 514 nm. The method is excellent for rapid prototyping of designs and we anticipate that it may be used to make embossing masters for lens fabrication into other materials.
Model database for determining dopant profiles from scanning capacitance microscope measurements
Authors: Marchiando J. F. , Kopanski J. J. , Lowney J. R.
Published: July 2002

To help correlate scanning capacitance microscope measurements of silicon with uniformly doped concentrations, model capacitance curves are calculated and stored in a database that depends on the probe-tip radius of curvature, the oxide thickness, and the dopant density. The oxide thicknesses range from 5 to 20 nm, the dopant concentrations range from 1017 to 1020 cm−3, and the probe-tip radius of curvature is set to 10 nm. The cone-shaped probe is oriented normal to the sample surface, so that the finite-element method in two dimensions may be used to solve Poisson’s equation in the semiconductor region and Laplace’s equation in the oxide and ambient regions. The equations are solved within the semi-classical quasistatic approximation, where capacitance measurement depends only on the charge due to majority carriers, with inversion and charge trapping effects being ignored. Comparison with one-dimensional-related models differs as much as 200% over the given doping range. For shallow gradient profiles satisfying quasiuniformity conditions, the database is used directly to find the doping profile. Converting a 512×512 point image takes less than 2 min.
Surface work function studies in porous silicon
Authors: Bhave Tejashree M. , Bhoraskar S. V.
Published: July 2002

Band structure studies in porous silicon provide useful information about the operative phenomenon responsible for its room temperature photoluminescence. We have measured the average surface work function, using a retarding field diode method in ultrahigh vacuum conditions, for porous silicon having different crystalline columnar dimensions. The average crystallite size was determined by grazing angle x-ray diffraction measurements; whereas the band gap was estimated from the photoluminescence measurements. Based on these results, different empirical band structural models are reviewed. Photoconductivity measurements in porous silicon also insinuate that the electrical resistivity of the surface of porous silicon is manipulated by the silicon complexes present on the surface. It has been concluded that, in addition to the quantum confinement, the surface molecular species dominantly control the behavior of photoluminescence and average surface work function of porous silicon.
Influence of growth conditions, inversion domains, and atomic hydrogen on growth of (0001_) GaN by molecular beam epitaxy
Authors: Myers T. H. , Hirsch L. S. , Romano L. T. , Richards-Babb M. R.
Published: July 2002

Growth of GaN by rf-plasma molecular beam epitaxy leads to different surface morphologies for nitrogen-stable growth versus gallium-stable growth. Nitrogen-stable growth produces a granular surface morphology with many samples having a significant density of pyramidal hillocks. In contrast, gallium-stable growth results in a flat surface morphology. The hillocks were directly linked to the presence of inversion domains which originated in the nucleation layer. Nitrogen-stable growth and growth under atomic hydrogen enhanced the growth rate of inversion domains with respect to the surrounding matrix, while growth under Ga-stable conditions resulted in a more nearly equal growth rate. Evidence is presented suggesting that hydrogen may stabilize the surface of growing GaN.
Ex situ formation of oxide-interlayer-mediated-epitaxial CoSi2 film using Ti capping
Authors: Kim Gi Bum , Kwak Joon Seop , Baik Hong Koo , Lee Sung-Man
Published: July 2002

A modified oxide mediated epitaxy process using a single deposition and ex situ annealing by Ti capping has been developed in this study. With pure Co on Shiraki oxide, the reaction between Co and Si did not occur even at 800 °C during ex situ annealing, because of the adsorption of oxygen on the Co film. However, when the pure Co on the Shiraki oxide was capped by Ti, a uniform Ti oxide surface layer was formed during the initial stage of annealing, which had a role to eliminate the adsorption of oxygen on the Co film. It led to uniform Co diffusion into the Si substrate through the Shiraki oxide, resulting in epitaxial CoSi2. A good channeling χmin value of 18% comparable to that of the Ti/Co bilayer system was measured in the epitaxial CoSi2 formed from this modified oxide mediated epitaxy process.
Characterization of organic solution deposited copper seed layers on Al(Cu) sputtered thin films
Authors: O’Keefe M. J. , Leedy K. D. , Grant J. T. , Fang M. , Gu H. , O’Keefe T. J.
Published: July 2002

Initial investigations into the influence of chemical composition and thermal treatments of sputtered Al(Cu) thin films on the subsequent deposition of copper seed layers from copper bearing organic solutions have been completed. The amount of Cu in the Al(Cu) films was varied from 0 to 2 wt % and it was determined that a slight improvement in organically deposited copper particle density occurred with increasing Cu concentration in the Al(Cu) film. A more significant influence on organic solution copper deposition was the segregation of Cu in the Al(Cu) toward the surface of the film during annealing. Annealed Al(Cu) films were found by x-ray photoelectron spectroscopy to have a measurable increase in the concentration of Cu near the surface which facilitated the nucleation of organically deposited copper. Broad face and cross sectional transmission electron microscopy of Al(Cu) films with and without organically deposited copper seed layers indicated that the cementation exchange reaction was confined to the near surface of the Al(Cu) films and that discrete, pure copper particles were deposited from the organic solution.
Ultrahigh density data storage in an organic film with a scanning tunneling microscope
Authors: Hou S. M. , Zhao X. Y. , Yang C. , Xue Z. Q. , Yang W. J. , Chen H. Y.
Published: July 2002

A nanometer-scale recording technique was demonstrated on N-(3-nitrobenzylidene)–p-phenylenediamine (NBPDA) organic thin films with a scanning tunneling microscope (STM). NBPDA thin films were fabricated by vacuum thermal deposition. The results of ultraviolet-visible absorption and infrared transmission spectra showed that the structure of the NBPDA film was the same as that of NBPDA crystal. An atomic force microscope was utilized to characterize the surface morphology of the NBPDA film. Data were recorded by applying voltage pulses between the tip and the substrate. The current–voltage characteristics measured by the STM indicated that the local electrical property changed from an insulating property into a metallic property after the data were written. Data marks, 1.4 nm in diameter, corresponded to a data storage density of 1012 bits/cm2. A preliminary calculation was presented to explain the recording mechanism.
Individual tip evaluation in Si field emitter arrays by electrostatic lens projector
Authors: Matsukawa T. , Kanemaru S. , Tokunaga K. , Itoh J.
Published: July 2002

Field emission from individual tips in a silicon field emitter array (FEA) has been directly evaluated by using an electrostatic lens projector. Uniformity of the emission sites in n- and p-type Si FEAs has been investigated and compared at various conditions. The number of the emission spots in the p-type FEA increased linearly with the increase in the total emission current, and the p-type FEA exhibited better uniformity of the emission spots especially under large emission currents than the n-type FEA. Furthermore, effects of the gas ambient on the emission uniformity were evaluated. The emission uniformity was improved dramatically by exposing C2H4 ambient during the field emission.
Superconductivity in Boron
Authors: Eremets Mikhail I. , Struzhkin Viktor V. , Mao Ho-kwang , Hemley Russell J.
Published: July 2002

Metals formed from light elements are predicted to exhibit intriguing states of electronic order. Of these materials, those containing boron are of considerable current interest because of their relatively high superconducting temperatures. We have investigated elemental boron to very high pressure using diamond anvil cell electrical conductivity techniques. We find that boron transforms from a nonmetal to a superconductor at about 160 gigapascals (GPa). The critical temperature of the transition increases from 6 kelvin (K) at 175 GPa to 11.2 K at 250 GPa, giving a positive pressure derivative of 0.05 K/GPa. Although the observed metallization pressure is compatible with the predictions of first-principles calculations, superconductivity in boron remains to be explored theoretically. The present results constitute a record pressure for both electrical conductivity studies and investigations of superconductivity in dense matter.
Regulation of SREBP Processing and Membrane Lipid Production by Phospholipids in
Drosophila
Authors: Dobrosotskaya I. Y. , Seegmiller A. C. , Brown M. S. , Goldstein J. L. , Rawson R. B.
Published: July 2002

Animal cells exert exquisite control over the physical and chemical properties of their membranes, but the mechanisms are obscure. We show that phosphatidylethanolamine, the major phospholipid in
Drosophila
, controls the release of sterol regulatory element–binding protein (SREBP) from
Drosophila
cell membranes, exerting feedback control on the synthesis of fatty acids and phospholipids. The finding that SREBP processing is controlled by different lipids in mammals and flies (sterols and phosphatidylethanolamine, respectively) suggests that an essential function of SREBP is to monitor cell membrane composition and to adjust lipid synthesis accordingly.
Neurons Put the Uncertainty Into Reaction Times
Authors: Barinaga Marcia
Published: July 2002

Researchers studying the response times of individual neurons have provided a physiological explanation for why the same individual can vary widely in how long it takes to respond to a stimulus. Their results are reported on (
page 427
) of this issue. The researchers invite you to test your own reaction time by downloading a 10-trial
demo
(1 MB, for Macintosh only).
Sequence Similarity Between the 73-Kilodalton Protein of Mammalian CPSF and a Subunit of Yeast Polyadenylation Factor I
Authors: Jenny Andreas , Minvielle-Sebastia Lionel , Preker Pascal J. , Keller Walter
Published: July 2002

The 3′ ends of most eukaryotic messenger RNAs are generated by endonucleolytic cleavage and polyadenylation. In mammals, the cleavage and polyadenylation specificity factor (CPSF) plays a central role in both steps of the processing reaction. Here, the cloning of the 73-kilodalton subunit of CPSF is reported. Sequence analyses revealed that a yeast protein (Ysh1) was highly similar to the 73-kD polypeptide. Ysh1 constitutes a new subunit of polyadenylation factor I (PFI), which has a role in yeast pre-mRNA 3′-end formation. This finding was unexpected because in contrast to CPSF, PFI is only required for the polyadenylation reaction. These results contribute to the understanding of how 3′-end processing factors may have evolved.
Src Structure Crystallizes 20 Years of Oncogene Research
Authors: Featherstone Carol
Published: July 2002

The first known cancer-causing gene is a Jekyll-and-Hyde gene called src, which is benign in normal cells but can turn dangerous when altered by a virus or by mutations. For 20 years, researchers have sought the controls for the Src protein's on-off switch. Two papers in last week's issue of Nature now reveal the crystal structure of the inactive forms of Src and a related protein, showing how this potentially dangerous molecule is restrained in normal cells.
A Porous Silicon-Based Optical Interferometric Biosensor
Authors: Lin Victor S.-Y. , Motesharei Kianoush , Dancil Keiki-Pua S. , Sailor Michael J. , Ghadiri M. Reza
Published: July 2002

A biosensor has been developed based on induced wavelength shifts in the Fabry-Perot fringes in the visible-light reflection spectrum of appropriately derivatized thin films of porous silicon semiconductors. Binding of molecules induced changes in the refractive index of the porous silicon. The validity and sensitivity of the system are demonstrated for small organic molecules (biotin and digoxigenin), 16-nucleotide DNA oligomers, and proteins (streptavidin and antibodies) at pico- and femtomolar analyte concentrations. The sensor is also highly effective for detecting single and multilayered molecular assemblies.
Inducible Repair of Thymine Glycol Detected by an Ultrasensitive Assay for DNA Damage
Authors: Le X. Chris , Xing James Z. , Lee Jane , Leadon Steven A. , Weinfeld Michael
Published: July 2002

An ultrasensitive assay for measuring DNA base damage is described that couples immunochemical recognition with capillary electrophoresis and laser-induced fluorescence detection. The method provides a detection limit of 3 × 10
−21
moles, an improvement of four to five orders of magnitude over current methods. Induction and repair of thymine glycols were studied in irradiated A549 cells (a human lung carcinoma cell line). Exposure of these cells to a low dose of radiation (0.25 Gray) 4 hours before a clinically relevant dose (2 Gray) enhanced removal of thymine glycols after the higher dose. These data provide evidence for an inducible repair response for radiation-induced damage to DNA bases.
The Effect of Spin Splitting on the Metallic Behavior of a Two-Dimensional System
Authors: Papadakis S. J. , De Poortere E. P. , Manoharan H. C. , Shayegan M. , Winkler R.
Published: July 2002

Experiments on a constant-density two-dimensional hole system in a gallium arsenide quantum well revealed that the metallic behavior observed in the zero–magnetic-field temperature dependence of the resistivity depends on the symmetry of the confinement potential and the resulting spin splitting of the valence band.
Complexity and the Nervous System
Authors: Koch Christof , Laurent Gilles
Published: July 2002

Advances in the neurosciences have revealed the staggering complexity of even “simple” nervous systems. This is reflected in their function, their evolutionary history, their structure, and the coding schemes they use to represent information. These four viewpoints need all play a role in any future science of “brain complexity.”
Climate Variability in Northwest Greece During the Last Interglacial
Authors: Frogley M. R. , Tzedakis P. C. , Heaton T. H. E.
Published: July 2002

Isotopic and palynological data over the period 115,000 to 135,000 years ago from a lacustrine sequence in northwest Greece show distinct oscillations during the intervals leading into and out of the full interglacial, whereas in between, changes were less pronounced but included a brief fluctuation. After peak interglacial conditions, temperatures decreased and precipitation increased in a series of steps. These data suggest that Eemian climate variability was similar to that of the Holocene both in terms of amplitude and, possibly, of pacing.
Coordinated Polar Localization of Auxin Efflux Carrier PIN1 by GNOM ARF GEF
Authors: Steinmann Thomas , Geldner Niko , Grebe Markus , Mangold Stefan , Jackson Catherine L. , Paris Sonia , Gälweiler Leo , Palme Klaus , Jürgens Gerd
Published: July 2002

The plant hormone auxin is transported in a polar manner along the shoot-root axis, which requires efflux carriers such as PIN1. Asymmetric localization of PIN1 develops from a random distribution in
Arabidopsis
early embryogenesis. Coordinated polar localization of PIN1 is defective in
gnom
embryos. GNOM is a membrane-associated guanine-nucleotide exchange factor on ADP-ribosylation factor G protein (ARF GEF). Thus, GNOM-dependent vesicle trafficking may establish cell polarity, resulting in polar auxin transport.
Visualization of Dioxygen Bound to Copper During Enzyme Catalysis
Authors: Wilmot C. M. , Hajdu J. , McPherson M. J. , Knowles P. F. , Phillips S. E. V.
Published: July 2002

X-ray crystal structures of three species related to the oxidative half of the reaction of the copper-containing quinoprotein amine oxidase from
Escherichia coli
have been determined. Crystals were freeze-trapped either anaerobically or aerobically after exposure to substrate, and structures were determined to resolutions between 2.1 and 2.4 angstroms. The oxidation state of the quinone cofactor was investigated by single-crystal spectrophotometry. The structures reveal the site of bound dioxygen and the proton transfer pathways involved in oxygen reduction. The quinone cofactor is regenerated from the iminoquinone intermediate by hydrolysis involving Asp
383
, the catalytic base in the reductive half-reaction. Product aldehyde inhibits the hydrolysis, making release of product the rate-determining step of the reaction in the crystal.
Contribution of Natural Amino Acid Substitutions in SHV Extended-Spectrum β-Lactamases to Resistance against Various β-Lactams
Authors: Randegger Corinne C. , Keller André , Irla Michel , Wada Akihito , Hächler Herbert
Published: July 2002

SHV extended-spectrum β-lactamases (ESBLs) arise through single amino acid substitutions in the parental enzyme, SHV-1. In order to evaluate the effect of genetic dissimilarities around the structural gene on MICs, we had previously devised an isogenic system of strains. Here, we present an extended version of the system that now allows assessment of all major types of SHV β-lactamases as well as of two types of promoters of various strengths. Moreover, we devised a novel vector, pCCR9, to eliminate interference of the selection marker. A substitution within the signal sequence, I8F found in SHV-7, slightly increased MICs, suggesting more efficient transfer of enzyme precursor into the periplasmic space. We also noted that combination of G238S and E240K yielded higher resistance than G238S alone. However, the influence of the additional E240K change was more pronounced with ceftazidime and aztreonam than with cefotaxime and ceftriaxone. The SHV enzymes characterized by the single change, D179N, such as SHV-8, turned out to be the weakest SHV ESBLs. Only resistance to ceftazidime was moderately increased compared to SHV-1.
In Vitro Interaction of Terbinafine with Itraconazole against Clinical Isolates of
Scedosporium prolificans
Authors: Meletiadis Joseph , Mouton Johan W. , Rodriguez-Tudela Juan L. , Meis Jacques F. G. M. , Verweij Paul E.
Published: July 2002

In order to develop new approaches for the chemotherapy of invasive infections caused by
Scedosporium prolificans
, the in vitro interaction between itraconazole and terbinafine against 20 clinical isolates was studied using a checkerboard microdilution method. Itraconazole and terbinafine alone were inactive against most isolates, but the combination was synergistic against 95 and 85% of isolates after 48 and 72 h of incubation, respectively. Antagonism was not observed. The MICs obtained with the terbinafine-itraconazole combination were within levels that can be achieved in plasma.
Faropenem Transport across the Renal Epithelial Luminal Membrane via Inorganic Phosphate Transporter Npt1
Authors: Uchino Hiroshi , Tamai Ikumi , Yabuuchi Hikaru , China Kayoko , Miyamoto Ken-ichi , Takeda Eiji , Tsuji Akira
Published: July 2002

We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a
Xenopus
oocyte expression system. Faropenem (an oral penem antibiotic) was transported via Npt1 with a Michaelis-Menten constant of 0.77 ± 0.34 mM in a sodium-independent but chloride ion-sensitive manner. When the concentration of chloride ions was increased, the transport activity of faropenem by Npt1 was decreased. Since the concentration gradient of chloride ions is in the lumen-to-intracellular direction, faropenem is expected to be transported from inside proximal tubular cells to the lumen. So, we tested the release of faropenem from
Xenopus
oocytes. The rate of efflux of faropenem from Npt1-expressing oocytes was about 9.5 times faster than that from control water-injected
Xenopus
oocytes. Faropenem transport by Npt1 was significantly inhibited by β-lactam antibiotics such as benzylpenicillin, ampicillin, cephalexin, and cefazolin to 24.9, 40.5, 54.4, and 26.2% of that for the control, respectively. Zwitterionic β-lactam antibiotics showed lesser inhibitory effects on faropenem uptake than anionic derivatives, indicating that Npt1 preferentially transports anionic compounds. Other anionic compounds, such as indomethacin and furosemide, and the anion transport inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid significantly inhibited faropenem uptake mediated by Npt1. In conclusion, our results suggest that Npt1 participates in the renal secretion of penem antibiotics.
Pharmacodynamic Assessment of Cefprozil against
Streptococcus pneumoniae
: Implications for Breakpoint Determinations
Authors: Nicolau David P. , Onyeji Cyprian O. , Zhong Mingkang , Tessier Pamela R. , Banevicius Mary Anne , Nightingale Charles H.
Published: July 2002

Cefprozil, an oral semisynthetic cephalosporin, is commonly utilized in the treatment of respiratory-tract infections in children. While this agent has provided acceptable clinical success over a number of years, this study was undertaken to better define its pharmacodynamic profile against
Streptococcus pneumoniae
. Nineteen clinical isolates of
S. pneumoniae
were utilized in the neutropenic murine thigh infection model. To simulate the pharmacokinetic profile of cefprozil in children, the renal function of mice was impaired with uranyl nitrate, and a commercially available cefprozil suspension (6 mg/kg of body weight) was administered orally every 12 h. Mice were infected with 10
6
to 10
7
CFU per thigh, and therapy was initiated 2 h later. At 0 and 24 h postinfection, thighs were harvested to determine bacterial density. Survival was assessed during 96 h of therapy. The magnitude of bacterial kill ranged from 0.5 to 4.4 log
10
CFU per thigh over 24 h, and the extent of microbial eradication was dependent on the MIC. Killing of more than 2.6 log
10
CFU per thigh was observed with MICs of ≤3 μg/ml, while either minimal killing or growth was detected with MICs of ≥4 μg/ml. Mortality in untreated control animals was 100%. Animals infected with strains for which the MICs were ≤2 μg/ml survived the infection, whereas MICs exceeding 2 μg/ml resulted in substantial mortality. These studies demonstrate the effectiveness of cefprozil against isolates of the pneumococcus for which the MICs are ≤2 μg/ml using a drug exposure typically observed in children. These data support a susceptibility breakpoint of ≤2 μg/ml for cefprozil.
Antileishmanial Activities of Stearylamine-Bearing Liposomes
Authors: Dey Tuhina , Anam Khairul , Afrin Farhat , Ali Nahid
Published: July 2002

Here we report the activity of liposomes comprising egg phosphatidylcholine (PC) and stearylamine (SA) against
Leishmania donovani
parasites. Both promastigotes and intracellular amastigotes in vitro and in vivo were susceptible to SA-PC liposomes. A single dose of 55 mg of SA-PC liposomes/animal could significantly reduce the hepatic parasite burden by 85 and 68% against recent and established experimental visceral leishmaniasis, respectively, suggesting their strong therapeutic potential.
High-Affinity Binding of Silybin Derivatives to the Nucleotide-Binding Domain of a
Leishmania tropica
P-Glycoprotein-Like Transporter and Chemosensitization of a Multidrug-Resistant Parasite to Daunomycin
Authors: Pérez-Victoria José M. , Pérez-Victoria F. Javier , Conseil Gwenaëlle , Maitrejean Mathias , Comte Gilles , Barron Denis , Di Pietro Attilio , Castanys Santiago , Gamarro Francisco
Published: July 2002

In order to overcome the multidrug resistance mediated by P-glycoprotein-like transporters in
Leishmania
spp., we have studied the effects produced by derivatives of the flavanolignan silybin and related compounds lacking the monolignol unit on (i) the affinity of binding to a recombinant C-terminal nucleotide-binding domain of the
L. tropica
P-glycoprotein-like transporter and (ii) the sensitization to daunomycin on promastigote forms of a multidrug-resistant
L. tropica
line overexpressing the transporter. Oxidation of the flavanonol silybin to the corresponding flavonol dehydrosilybin, the presence of the monolignol unit, and the addition of a hydrophobic substituent such as dimethylallyl, especially at position 8 of ring A, considerably increased the binding affinity. The in vitro binding affinity of these compounds for the recombinant cytosolic domain correlated with their modulation of drug resistance phenotype. In particular, 8-(3,3-dimethylallyl)-dehydrosilybin effectively sensitized multidrug-resistant
Leishmania
spp. to daunomycin. The cytosolic domains are therefore attractive targets for the rational design of inhibitors against P-glycoprotein-like transporters.
Antipneumococcal Activity of Ertapenem (MK-0826) Compared to Those of Other Agents
Authors: Pankuch Glenn A. , Davies Todd A. , Jacobs Michael R. , Appelbaum Peter C.
Published: July 2002

The activities of ertapenem (MK-0826) and eight other agents against a range of penicillin-susceptible and -resistant pneumococci were tested by determination of MICs by the microdilution method and by the time-kill methodology. For 125 penicillin-susceptible, 74 penicillin-intermediate, and 86 penicillin-resistant pneumococci, the MICs at which 50% of isolates are inhibited (MIC
50
s) and MIC
90
s, as determined by the microdilution method, were as follows: for ertapenem, 0.016 and 0.03, 0.125 and 0.5, and 0.5 and 1.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for amoxicillin, ≤0.016 and 0.03, 0.25 and 1.0, and 2.0 and 2.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for cefprozil, 0.125 and 0.25, 1.0 and 8.0, and 16.0 and 16.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for cefepime, ≤0.016 and 0.06, 0.5 and 1.0, and 1.0 and 2.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for ceftriaxone, ≤0.016 and 0.06, 0.25 and 1.0, and 1.0 and 2.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for imipenem, ≤0.008 and ≤0.008, 0.03 and 0.25, and 0.25 and 0.25 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for meropenem, ≤0.008 and 0.016, 0.125 and 0.5, and 0.5 and 1.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; and for clarithromycin, 1.0 and >32.0, 1.0 and >32.0, and >32.0 and >32.0 μg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively. For 64 strains for which quinolone MICs were increased (ciprofloxacin MICs, ≥4.0 μg/ml), the MIC
90
of ertapenem was 1.0 μg/ml and the MIC
90
s of the other β-lactams tested and clarithromycin were >32.0 μg/ml. Against four penicillin-susceptible, four penicillin-intermediate, and four penicillin-resistant strains, testing by the time-kill methodology showed that ertapenem at two times the MIC was bacteriostatic (99% killing) after 12 h and bactericidal (99.9% killing) against all strains by 24 h, with 90% killing of all strains at two times the MIC after 6 h. At the MIC, ertapenem was bacteriostatic against all strains tested after 24 h. Although the bactericidal activity of imipenem at the MIC after 24 h was significantly greater than that of ertapenem, the kinetics of the two drugs at two times the MIC were similar after 24 h. The killing kinetics of clarithromycin were slower than those of ertapenem and other agents, with clarithromycin at two times the MIC having bactericidal activity against seven of eight macrolide-susceptible strains after 24 h.
Lack of Interaction of Fluoroquinolones with Lipopolysaccharides
Authors: Lindner B. , Wiese A. , Brandenburg K. , Seydel U. , Dalhoff A.
Published: July 2002

Fluoroquinolones are known to chelate with di- and trivalent cations, and it has accordingly been claimed that they perturb the integrity of the outer membrane (OM) of gram-negative bacteria. So far, chelation has not been assessed in biologically relevant test systems. Therefore, we investigated the interaction of ciprofloxacin and moxifloxacin in the absence and presence of Mg
2+
with whole bacteria and isolated lipopolysaccharide (LPS) from various rough mutant strains of
Salmonella enterica
chemotypes by applying different biophysical techniques. We found that the fluoroquinolones did not disturb the integrity of the OM and neither were incorporated into LPS monolayers nor displaced Ca
2+
from LPS monolayers, suggesting that chelation of fluoroquinolones with divalent cations does not contribute to the antibacterial effect of fluoroquinolones.
Possible Interactions within a Methanotrophic-Heterotrophic Groundwater Community Able To Transform Linear Alkylbenzenesulfonates
Authors: Hršak Dubravka , Begonja Ana
Published: July 2002

The relationships and interactions within a methanotrophic-heterotrophic groundwater community were studied in a closed system (shake culture) in the presence of methane as the primary carbon and energy source and with the addition of the pure linear alkylbenzenesulfonate (LAS) congener 2-[4-(sulfophenyl)]decan as a cometabolic substrate. When cultured under different conditions, this community was shown to be a stable association, consisting of one obligate type II methanotroph and four or five heterotrophs possessing different nutritional and physiological characteristics. The results of experiments examining growth kinetics and nutritional relationships suggested that a number of complex interactions existed in the community in which the methanotroph was the only member able to grow on methane and to cometabolically initiate LAS transformation. These growth and metabolic activities of the methanotroph ensured the supply of a carbon source and specific nutrients which sustained the growth of four or five heterotrophs. In addition to the obligatory nutritional relationships between the methanotroph and heterotrophs, other possible interactions resulted in the modification of basic growth parameters of individual populations and a concerted metabolic attack on the complex LAS molecule. Most of these relationships conferred beneficial effects on the interacting populations, making the community adaptable to various environmental conditions and more efficient in LAS transformation than any of the individual populations alone.