bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomic force microscopy observation of TiO2 films deposited by dc reactive sputtering
Authors: Takahashi T. , Nakabayashi H. , Terasawa T. , Masugata K.
Published: July 2002

A bombardment of energetic particles such as secondary electrons and recoiled ions ejected from the target plane is a very useful technique for modifying the structure of the film in reactive sputtering. It leads to interesting effects such as enhancement of reactivity, adatom mobility, and atomic peening. Therefore, the state on the surface of the as-deposited film may significantly depend on the bombardment condition. So, in this study, the relationship between the bombardment condition and the surface morphology of TiO2 films has been investigated in detail. TiO2 films with a thickness of about 0.8–2.3 μm were deposited by dc reactive sputtering on glass-slide substrates. The surface roughness of films was measured with atomic-force microscopy. The roughness parameter Ra on the surface of TiO2 films depended on the energy and the number of bombarding particles. After increasing the energy and the number of bombarding particles, Ra increased from 10 to 77 nm. Consequently, it was found that the surface morphology of TiO2 films strongly affected the plasma exposure to the growing film.
Molecular drag model based on differential reduction of the Kruger–Shapiro equations
Authors: Helmer J. C. , Levi G.
Published: July 2002

The history of the method of differential probability in molecular flow is reviewed, beginning with the little known derivation by D. Santeler (5th Annual Symposium on Space Environmental Simulation, Arnold Air Force Station, TN, May, 1964), based on the equation of C. W. Oatley [Br. J. Appl. Phys. 8, 15 (1957)]. This method contains the aperture correction within the theory, without phenomenological assumptions. A new equation of this type, for molecular pumping, is derived by differential reduction of the Kruger–Shapiro equations. A simple solution of the differential equations yields results of good accuracy for engineering use. The physical characteristics of molecular pumping are clarified by describing the pressure distribution within the pumping tube as if it were a conductance. By this method the calculated performance of a model pump is shown to be in satisfactory agreement with a Clausing-type solution from a previous publication.
Bi epitaxy on polar InSb(111)A/B faces
Authors: Cho Sunglae , Um Young-Ho , Kim Yunki , Wong George K. L. , Ketterson J. B. , Hong Jung-Il
Published: July 2002

Bi thin films have been grown on InSb(111)A/B substrates using molecular beam epitaxy. We have observed different Bi atomic surface structures on polar InSb(111)A and B faces as well as thickness dependent surface structures on the A face. Bi deposited on InSb(111)B shows a (1×1) surface structure, i.e., no surface reconstruction. However, Bi on InSb(111)A shows a (2×2) structure for thicknesses less than 16 Å, thereafter changing to a (1×1) structure. On both surfaces, Bi grows in a layer-by-layer growth mode with high crystallinity and sharp interfaces.
Dynamics of the ion beam induced nitridation of silicon
Authors: Deenapanray Prakash N. K.
Published: July 2002

High-resolution Rutherford backscattering and channeling has been used to study the energy and angular dependence of the ion beam induced nitridation of Si in a secondary ion mass spectrometry system. The nitridation of Si is characterized by two critical angles θc1 and θc2, corresponding to the formation of stoichiometric and overstoichiometric Si-nitride layers, respectively. For the N2+ bombardment in the 10 to 13.5 keV range, θc1 changes from 40° to 45°, while θc2 changes from 28° to 30°. Further, strong oscillations in the secondary ion signal, observed for angles of incidence below θc2, are directly related to charging of the Si-nitride surface. We demonstrate that the response of the Si-nitride layer under ion bombardment during the transient stage of nitridation can be described by a second order differential equation.
Characteristics of a direct metal ion beam deposition source
Authors: Kim Daeil , Kim Steven
Published: July 2002

In this study, we examine the performance of a direct metal ion beam deposition (DMIBD) system which uses a Cs–mordenite pellet as the ion source. We describe design aspects of DMIBD and process parameters such as secondary ion yields, secondary ion energy distributions, secondary ion to atom arrival ratios and deposition rates for C, Al, Si, Ni, Cu, Ta, and W targets. During deposition, the secondary negative metal ion yield strongly depends on the primary Cs+ ion does and bombarding energy. Also, the deposition rate and ion to atom arrival ratios for various targets can be controlled by adjusting the primary Cs+ ion dose, Cs+ ion bombarding energy, and ion beam energy to fit the desired application.
Effects of deposition temperature and seed layer on the optical properties of lead zirconate titanate films
Authors: Kang Hee-Soo , Lee Won-Jong
Published: July 2002

Lead zirconate titanate (PZT) films were deposited on indium tin oxide coated Corning 7059 glass by rf magnetron sputtering at the temperatures ranging from room temperature to 500 °C. The crack-free PZT films with pure perovskite phase could be successfully fabricated through postannealing at 650 °C for 10 min. The films deposited at 400 °C and subsequently postannealed at 650 °C showed the best optical properties with a linear electro-optic coefficient of 80 pm/V and a propagation loss of 2 dB/cm. It was found from our study on the change of crystalline orientation with film thickness that the 50 nm thick PZT thin film annealed at 650 °C exhibited (100) preferred orientation. Using this thin film as a seed layer, we could fabricate PZT films with (100) preferred orientation that showed higher remnant polarization (2Pr=46 μC/cm2) and dielectric constant (ε=1400) compared with randomly oriented films. This highly oriented PZT film also showed an excellent linear electro-optic coefficient of 109 pm/V that is comparable with the value of the PZT film epitaxially grown on the single crystal substrate.
ZnSe Thin Films Deposited by the Chemical Bath Deposition Method, by XPS
Authors: Chaparro Antonio M. , Maffiotte Cesar
Published: July 2002

Surface and bulk composition of ZnSe thin films deposited by the chemical bath deposition (CBD) method, are analyzed with x-ray photoelectron spectroscopy (XPS). In-depth composition information is obtained with angle-resolved XPS (ARXPS) and sputtering-assisted XPS. The films show excess Zn proportion (Zn/Se=1.1) due to an amount of ZnO (or OH−). ARXPS and sputtering assisted measurements show that the Zn excess is higher in the layers closer to the substrate, i.e., layers deposited at the beginning of the deposition process. A deposition mechanism most active at the beginning is responsible for the competitive deposition of ZnO. Other minority components in the films are surface SeO2, from ZnSe oxidation in air, bulk atomic Se, from oxidation of ZnSe and/or selenide bath precursors, and atomic Zn on layers closer to the substrate surface, from the initial CBD reaction.
Development of a computerized method for identifying the posteroanterior and lateral views of chest radiographs by use of a template matching technique
Authors: Arimura Hidetaka , Katsuragawa Shigehiko , Li Qiang , Ishida Takayuki , Doi Kunio
Published: July 2002

In picture archiving and communications systems (PACS) or digital archiving systems, the information on the posteroanterior (PA) and lateral views for chest radiographs is often not recorded or is recorded incorrectly. However, it is necessary to identify the PA or lateral view correctly and automatically for quantitative analysis of chest images for computer‐aided diagnosis. Our purpose in this study was to develop a computerized method for correctly identifying either PA or lateral views of chest radiographs. Our approach is to examine the similarity of a chest image with templates that represent the average chest images of the PA or lateral view for various types of patients. By use of a template matching technique with nine template images for patients of different size in two steps, correlation values were obtained for determining whether a chest image is either a PA or a lateral view. The templates for PA and lateral views were prepared from 447 PA and 200 lateral chest images. For a validation test, this scheme was applied to 1,000 test images consisting of 500 PA and 500 lateral chest radiographs, which are different from training cases. In the first step, 924 (92.4%) of the cases were correctly identified by comparison of the correlation values obtained with the three templates for medium‐size patients. In the second step, the correlation values with the six templates for small and large patients were compared, and all of the remaining unidentifiable cases were identified correctly.
Image quality evaluation of flat panel and image intensifier digital magnification in x‐ray fluoroscopy
Authors: Srinivas Yogesh , Wilson David L.
Published: July 2002

Interventional devices used in radiology often have dimensions on the order of a pixel, and radiologists resort to image magnification to better visualize such small devices. Traditional image intensifier (II) systems use analog magnification with x‐ray exposure inversely proportional to the area of field of view (FOV) so as to maintain light output for the camera. Analog magnification is impossible with flat panel (FP) detectors, and images must be magnified using digital interpolation that does not reduce the pixel partial area effect for small devices. We quantitatively investigated image quality of digital and analog magnification using a clinically relevant task of detecting a partially deployed stent in x‐ray fluoroscopy image sequences that were created using realistic detector models. Using the standard exposure strategy for II analog magnification, exposure was increased from a nominal 43.65 nGy (5.0 μR) per frame at 23 cm FOV to 79.9 nGy (9.15 μR) per frame and 117.81 nGy (13.49 μR) per frame at 17 cm and 14 cm FOV, respectively. Contrast sensitivity improved significantly by and with the 17 cm and 14 cm FOV, respectively. Exposure for digitally magnified images was varied in an adaptive forced choice experiment so as to match performance with II analog magnification. For digital magnification, bilinear interpolation was used to give magnified stents sizes equivalent to those in the analog magnified images. For equivalent image quality, FP required and per frame at normal, and the two magnification modes, respectively. Hence, FP with digital magnification gives significant dose savings of and at the normal and highest magnification modes, respectively. Digitally magnified II images required exposures of and per frame for the two magnifications levels, respectively, giving no significant dose savings. A spatiotemporal human observer model based on signal detection theory successfully predicted the human data and was used to predict other conditions associated with image magnification. Model predictions quantitatively showed that magnification is most useful when signal size is relatively small and that FP digital magnification can improve image quality for the stent deployment task without increasing exposure. In conclusion, the results show that FP digital magnification can be useful and dose efficient as compared to analog magnification.
A geometric theory of rapidly spinning tops, tippe tops, and footballs
Authors: Soodak Harry
Published: July 2002

A perturbative geometric theory of rapidly spinning tops is presented and applied to gyroscopes supported against gravity at a fixed point, tippe tops with sliding friction, the motion of a well-thrown football pass, and the effect of spin-drag torques. The theory provides a conceptually simple and formally straightforward analysis of the smoothed variation of the angular momentum vector, and of the angle between it and the symmetry axis.
Majorana solution of the Thomas–Fermi equation
Authors: Esposito Salvatore
Published: July 2002

We report on an original method, due to Majorana, that leads to a semi-analytical series solution of the Thomas–Fermi equation with appropriate boundary conditions in terms of only one quadrature. We also deduce a general formula for such a solution that avoids numerical integration, but is expressed in terms of the roots of a polynomial equation.
The clear speech effect for non-native listeners
Authors: Bradlow Ann R. , Bent Tessa
Published: July 2002

Previous work has established that naturally produced clear speech is more intelligible than conversational speech for adult hearing-impaired listeners and normal-hearing listeners under degraded listening conditions. The major goal of the present study was to investigate the extent to which naturally produced clear speech is an effective intelligibility enhancement strategy for non-native listeners. Thirty-two non-native and 32 native listeners were presented with naturally produced English sentences. Factors that varied were speaking style (conversational versus clear), signal-to-noise ratio (-4 versus -8 dB) and talker (one male versus one female). Results showed that while native listeners derived a substantial benefit from naturally produced clear speech (an improvement of about 16 rau units on a keyword-correct count), non-native listeners exhibited only a small clear speech effect (an improvement of only 5 rau units). This relatively small clear speech effect for non-native listeners is interpreted as a consequence of the fact that clear speech is essentially native-listener oriented, and therefore is only beneficial to listeners with extensive experience with the sound structure of the target language.
Combined Helmholtz equation–least squares method for reconstructing acoustic radiation from arbitrarily shaped objects
Authors: Wu Sean F. , Zhao Xiang
Published: July 2002

A combined Helmholtz equation–least squares (CHELS) method is developed for reconstructing acoustic radiation from an arbitrary object. This method combines the advantages of both the HELS method and the Helmholtz integral theory based near-field acoustic holography (NAH). As such it allows for reconstruction of the acoustic field radiated from an arbitrary object with relatively few measurements, thus significantly enhancing the reconstruction efficiency. The first step in the CHELS method is to establish the HELS formulations based on a finite number of acoustic pressure measurements taken on or beyond a hypothetical spherical surface that encloses the object under consideration. Next enough field acoustic pressures are generated using the HELS formulations and taken as the input to the Helmholtz integral formulations implemented through the boundary element method (BEM). The acoustic pressure and normal component of the velocity at the discretized nodes on the surface are then determined by solving two matrix equations using singular value decomposition (SVD) and regularization techniques. Also presented are in-depth analyses of the advantages and limitations of the CHELS method. Examples of reconstructing acoustic radiation from separable and nonseparable surfaces are demonstrated.
Prandtl number and thermoacoustic refrigerators
Authors: Tijani M. E. H. , Zeegers J. C. H. , de Waele A. T. A. M.
Published: July 2002

From kinetic gas theory, it is known that the Prandtl number for hard-sphere monatomic gases is 2/3. Lower values can be realized using gas mixtures of heavy and light monatomic gases. Prandtl numbers varying between 0.2 and 0.67 are obtained by using gas mixtures of helium–argon, helium–krypton, and helium–xenon. This paper presents the results of an experimental investigation into the effect of Prandtl number on the performance of a thermoacoustic refrigerator using gas mixtures. The measurements show that the performance of the refrigerator improves as the Prandtl number decreases. The lowest Prandtl number of 0.2, obtained with a mixture containing 30% xenon, leads to a coefficient of performance relative to Carnot which is 70% higher than with pure helium.
Supernova Remnant OH Masers: Signposts of Cosmic Collision
Authors: Wardle Mark , Yusef-Zadeh Farhad
Published: July 2002

A supernova explosion, the final death throe of a massive star, creates an expanding bubble of hot gas that overruns up the surrounding medium. When a supernova remnant encounters a dense interstellar cloud, the compression may trigger gravitational collapse and the formation of a new generation of stars. This event can be detected through intense stimulated emission in the 1720-megahertz transition of the hydroxyl radical, OH, which yields unique insights into the physical processes and conditions occurring during the interaction.
The Structure of Haplotype Blocks in the Human Genome
Authors: Gabriel Stacey B. , Schaffner Stephen F. , Nguyen Huy , Moore Jamie M. , Roy Jessica , Blumenstiel Brendan , Higgins John , DeFelice Matthew , Lochner Amy , Faggart Maura , Liu-Cordero Shau Neen , Rotimi Charles , Adeyemo Adebowale , Cooper Richard , Ward Ryk , Lander Eric S. , Daly Mark J. , Altshuler David
Published: July 2002

Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed. The boundaries of blocks and specific haplotypes they contain are highly correlated across populations. We demonstrate that such haplotype frameworks provide substantial statistical power in association studies of common genetic variation across each region. Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease.
Oscillations and Sparsening of Odor Representations in the Mushroom Body
Authors: Perez-Orive Javier , Mazor Ofer , Turner Glenn C. , Cassenaer Stijn , Wilson Rachel I. , Laurent Gilles
Published: July 2002

In the insect olfactory system, oscillatory synchronization is functionally relevant and reflects the coherent activation of dynamic neural assemblies. We examined the role of such oscillatory synchronization in information transfer between networks in this system. The antennal lobe is the obligatory relay for olfactory afferent signals and generates oscillatory output. The mushroom body is responsible for formation and retrieval of olfactory and other memories. The format of odor representations differs significantly across these structures. Whereas representations are dense, dynamic, and seemingly redundant in the antennal lobe, they are sparse and carried by more selective neurons in the mushroom body. This transformation relies on a combination of oscillatory dynamics and intrinsic and circuit properties that act together to selectively filter and synthesize the output from the antennal lobe. These results provide direct support for the functional relevance of correlation codes and shed some light on the role of oscillatory synchronization in sensory networks.
Visualization and Functional Analysis of RNA-Dependent RNA Polymerase Lattices
Authors: Lyle John M. , Bullitt Esther , Bienz Kurt , Kirkegaard Karla
Published: July 2002

Positive-strand RNA viruses such as poliovirus replicate their genomes on intracellular membranes of their eukaryotic hosts. Electron microscopy has revealed that purified poliovirus RNA-dependent RNA polymerase forms planar and tubular oligomeric arrays. The structural integrity of these arrays correlates with cooperative RNA binding and RNA elongation and is sensitive to mutations that disrupt intermolecular contacts predicted by the polymerase structure. Membranous vesicles isolated from poliovirus-infected cells contain structures consistent with the presence of two-dimensional polymerase arrays on their surfaces during infection. Therefore, host cytoplasmic membranes may function as physical foundations for two-dimensional polymerase arrays, conferring the advantages of surface catalysis to viral RNA replication.
Insights into Collisional Magmatism from Isotopic Fingerprints of Melting Reactions
Authors: Knesel Kurt M. , Davidson Jon P.
Published: July 2002

Piston-cylinder experiments in the granite system demonstrate that a variety of isotopically distinct melts can arise from progressive melting of a single source. The relation between the isotopic composition of Sr and the stoichiometry of the observed melting reactions suggests that isotopic signatures of anatectic magmas can be used to infer melting reactions in natural systems. Our results also indicate that distinct episodes of dehydration and fluid-fluxed melting of a single, metapelitic source region may have contributed to the bimodal geochemistry of crustally derived leucogranites of the Himalayan orogen.
Coherent Spin Oscillations in a Disordered Magnet
Authors: Ghosh S. , Parthasarathy R. , Rosenbaum T. F. , Aeppli G.
Published: July 2002

Most materials freeze when cooled to sufficiently low temperature. We find that magnetic dipoles randomly distributed in a solid matrix condense into a spin liquid with spectral properties on cooling that are the diametric opposite of those for conventional glasses. Measurements of the nonlinear magnetic dynamics in the low-temperature liquid reveal the presence of coherent spin oscillations composed of hundreds of spins with lifetimes of up to 10 seconds. These excitations can be labeled by frequency and manipulated by the magnetic fields from a loop of wire and can permit the encoding of information at multiple frequencies simultaneously.
Regulation of the Different Chromatin States of Autosomes and X Chromosomes in the Germ Line of
C. elegans
Authors: Fong Youyi , Bender Laurel , Wang Wenchao , Strome Susan
Published: July 2002

The Maternal-Effect Sterile (MES) proteins are essential for germline viability in
Caenorhabditis elegans
. Here, we report that MES-4, a SET-domain protein, binds to the autosomes but not to the X chromosomes. MES-2, MES-3, and MES-6 are required to exclude MES-4 and markers of active chromatin from the X chromosomes. These findings strengthen the emerging view that in the
C. elegans
germ line, the X chromosomes differ in chromatin state from the autosomes and are generally silenced. We propose that all four MES proteins participate in X-chromosome silencing, and that the role of MES-4 is to exclude repressors from the autosomes, thus enabling efficient repression of the Xs.
Antibody-Based Bio-Nanotube Membranes for Enantiomeric Drug Separations
Authors: Lee Sang Bok , Mitchell David T. , Trofin Lacramioara , Nevanen Tarja K. , Söderlund Hans , Martin Charles R.
Published: July 2002

Synthetic bio-nanotube membranes were developed and used to separate two enantiomers of a chiral drug. These membranes are based on alumina films that have cylindrical pores with monodisperse nanoscopic diameters (for example, 20 nanometers). Silica nanotubes were chemically synthesized within the pores of these films, and an antibody that selectively binds one of the enantiomers of the drug was attached to the inner walls of the silica nanotubes. These membranes selectively transport the enantiomer that specifically binds to the antibody, relative to the enantiomer that has lower affinity for the antibody. The solvent dimethyl sulfoxide was used to tune the antibody binding affinity. The enantiomeric selectivity coefficient increases as the inside diameter of the silica nanotubes decreases.
Evolution of the Gene Network Underlying Wing Polyphenism in Ants
Authors: Abouheif Ehab , Wray Gregory A.
Published: July 2002

Wing polyphenism in ants evolved once, 125 million years ago, and has been a key to their amazing evolutionary success. We characterized the expression of several genes within the network underlying the wing primordia of reproductive (winged) and sterile (wingless) ant castes. We show that the expression of several genes within the network is conserved in the winged castes of four ant species, whereas points of interruption within the network in the wingless castes are evolutionarily labile. The simultaneous evolutionary lability and conservation of the network underlying wing development in ants may have played an important role in the morphological diversification of this group and may be a general feature of polyphenic development and evolution in plants and animals.
Conformational Dynamics in a Dipeptide After Single-Mode Vibrational Excitation
Authors: Dian Brian C. , Longarte Asier , Zwier Timothy S.
Published: July 2002

The dynamics of conformational isomerization are explored in a methyl-capped dipeptide,
N
-acetyl-tryptophan methyl amide (NATMA), using infrared-ultraviolet (IR-UV) hole-filling and IR-induced population transfer spectroscopies. IR radiation selectively excites individual NH stretch vibrational fundamentals of single conformations of the molecule in the early portions of a gas-phase expansion, and then this excited population is collisionally recooled into its conformational minima for subsequent conformation-specific detection. Efficient isomerization is induced by the IR excitation that redistributes population between the same conformations that have population in the absence of IR excitation. The quantum yields for transfer of the population into the various conformational minima depend uniquely on which conformation is excited and on which NH stretch vibration is excited within a given conformation.
The Science of ART
Authors: Schultz Richard M. , Williams Carmen J.
Published: July 2002

The methods of gamete manipulation used in assisted reproductive technology (ART) are rapidly proliferating and in some instances outpacing the underlying science. In this review, we discuss two major advances in the ART laboratory—intracytoplasmic sperm injection and extended embryo culture before embryo transfer. We outline the rationale for these approaches, discuss results of experiments obtained from animal model systems and human preimplantation embryos that provide the scientific basis for these procedures, and point out potential concerns that have arisen from these studies.
Target-Selected Inactivation of the Zebrafish
rag1
Gene
Authors: Wienholds Erno , Schulte-Merker Stefan , Walderich Brigitte , Plasterk Ronald H. A.
Published: July 2002

The zebrafish has become a favorite organism for genetic analysis of vertebrate development, but methods for generating mutants by reverse genetic approaches have been lacking. We report a method to obtain stable mutants of a gene based on knowledge of the gene sequence only. Parental fish were mutagenized with
N
-ethyl-
N
-nitrosourea; in 2679 F
1
fish, the
rag1
gene was analyzed for heterozygous mutations by resequencing. In total, we found 15 mutations: 9 resulted in amino acid substitutions and 1 resulted in a premature stop codon. This truncation mutant was found to be homozygous viable and defective in V(D)J joining. Although presumably immune deficient, these homozygous
rag1
mutant fish are able to reach adulthood and are fertile. As sperm samples from all 2679 F
1
fish were collected and cryopreserved, we have in principle generated a mutant library from which mutants of most zebrafish genes can be isolated.
Two-Dimensional X-ray Waveguides and Point Sources
Authors: Pfeiffer F. , David C. , Burghammer M. , Riekel C. , Salditt T.
Published: July 2002

We show that resonant coupling of synchrotron beams into suitable nanostructures can be used for the generation of coherent x-ray point sources. A two-dimensionally confining x-ray waveguide structure has been fabricated by e-beam lithography. By shining a parallel undulator beam onto the structure, a discrete set of resonant modes can be excited in the dielectric cavity, depending on the two orthogonal coupling angles between the beam and the waveguide interfaces. The resonant excitation of the modes is evidenced from the characteristic set of coupling angles as well as the observed far-field pattern. The x-ray nanostructure may be used as coherent x-ray point sources with a beam cross section in the nanometer range.
Penetration, Adhesion, and Fusion in Mammalian Sperm-Egg Interaction
Authors: Primakoff Paul , Myles Diana G.
Published: July 2002

Fertilization is the sum of the cellular mechanisms that pass the genome from one generation to the next and initiate development of a new organism. A typical, ovulated mammalian egg is enclosed by two layers: an outer layer of ∼5000 cumulus cells and an inner, thick extracellular matrix, the zona pellucida. To reach the egg plasma membrane, sperm must penetrate both layers in steps requiring sperm motility, sperm surface enzymes, and probably sperm-secreted enzymes. Sperm also bind transiently to the egg zona pellucida and the egg plasma membrane and then fuse. Signaling in the sperm is induced by sperm adhesion to the zona pellucida, and signaling in the egg by gamete fusion. The gamete molecules and molecular interactions with essential roles in these events are gradually being discovered.
Storage of Methane and Freon by Interstitial van der Waals Confinement
Authors: Atwood Jerry L. , Barbour Leonard J. , Jerga Agoston
Published: July 2002

A known host-guest assembly, organized only by means of relatively weak dispersive forces, exhibits hitherto unappreciated thermal stability. The hexagonal close-packed arrangement of calix[4]arene contains lattice voids that can occlude small, highly volatile molecules. This host-guest system can be exploited to retain a range of freons, as well as methane, not only well above their normal boiling points, but also at relatively high temperatures and low pressures. The usually overlooked van der Waals interactions in organic crystals can indeed be used in a highly stable supramolecular system for gas storage.
Activation of
Drosophila
Toll During Fungal Infection by a Blood Serine Protease
Authors: Ligoxygakis Petros , Pelte Nadège , Hoffmann Jules A. , Reichhart Jean-Marc
Published: July 2002

Drosophila
host defense to fungal and Gram-positive bacterial infection is mediated by the
Spaetzle/Toll/cactus
gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate–induced mutations in the
persephone
gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.
Global Distribution of Neutrons from Mars: Results from Mars Odyssey
Authors: Feldman W. C. , Boynton W. V. , Tokar R. L. , Prettyman T. H. , Gasnault O. , Squyres S. W. , Elphic R. C. , Lawrence D. J. , Lawson S. L. , Maurice S. , McKinney G. W. , Moore K. R. , Reedy R. C.
Published: July 2002

Global distributions of thermal, epithermal, and fast neutron fluxes have been mapped during late southern summer/northern winter using the Mars Odyssey Neutron Spectrometer. These fluxes are selectively sensitive to the vertical and lateral spatial distributions of H and CO
2
in the uppermost meter of the martian surface. Poleward of ±60° latitude is terrain rich in hydrogen, probably H
2
O ice buried beneath tens of centimeter-thick hydrogen-poor soil. The central portion of the north polar cap is covered by a thick CO
2
layer, as is the residual south polar cap. Portions of the low to middle latitudes indicate subsurface deposits of chemically and/or physically bound H
2
O and/or OH.
Sustaining Fisheries Yields Over Evolutionary Time Scales
Authors: Conover David O. , Munch Stephan B.
Published: July 2002

Fishery management plans ignore the potential for evolutionary change in harvestable biomass. We subjected populations of an exploited fish (
Menidia menidia
) to large, small, or random size-selective harvest of adults over four generations. Harvested biomass evolved rapidly in directions counter to the size-dependent force of fishing mortality. Large-harvested populations initially produced the highest catch but quickly evolved a lower yield than controls. Small-harvested populations did the reverse. These shifts were caused by selection of genotypes with slower or faster rates of growth. Management tools that preserve natural genetic variation are necessary for long-term sustainable yield.
In Vitro Increase in Chloroquine Accumulation Induced by Dihydroethano- and Ethenoanthracene Derivatives in
Plasmodium falciparum
-Parasitized Erythrocytes
Authors: Pradines Bruno , Alibert Sandrine , Houdoin Carole , Santelli-Rouvier Christiane , Mosnier Joel , Fusai Thierry , Rogier Christophe , Barbe Jacques , Parzy Daniel
Published: July 2002

The effects of a series of dihydroethano- and ethenoanthracene derivatives on chloroquine (CQ) accumulation in CQ-susceptible strain 3D7 and CQ-resistant clone W2 were assessed. The levels of CQ accumulation increased little or none in CQ-susceptible strain 3D7 and generally increased markedly in CQ-resistant strain W2. At 10 μM, 28 compounds yielded cellular accumulation ratios (CARs) greater than that observed with CQ alone in W2. At 10 μM, in strain W2, 21 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 15 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 13 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 9 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 μM, 17 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 12 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 6 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 3 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 μM, 17 of 31 compounds were more potent inducers of CQ accumulation than verapamil and 12 of 31 compounds were more potent inducers of CQ accumulation than promethazine. The nature of the basic group seems to be associated with increases in the levels of CQ accumulation. At 1 and 10 μM, 10 of 14 and 13 of 14 compounds with amino group (amines and diamines), respectively, had CARs ≥3, while at 1 and 10 μM, only 1 of the 13 derivatives with amido groups had CARs ≥3. Among 12 of the 31 compounds which were more active inducers of CQ accumulation than promethazine at 1 μM, 10 had amino groups and 1 had an amido group.
Comparative Intracellular (THP-1 Macrophage) and Extracellular Activities of β-Lactams, Azithromycin, Gentamicin, and Fluoroquinolones against
Listeria monocytogenes
at Clinically Relevant Concentrations
Authors: Carryn Stéphane , Van Bambeke Françoise , Mingeot-Leclercq Marie-Paule , Tulkens Paul M.
Published: July 2002

The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin, and moxifloxacin against intracellular hemolysin-positive
Listeria monocytogenes
were measured in human THP-1 macrophages and were compared with the extracellular activities observed in broth. All extracellular concentrations were adjusted to explore ranges that are clinically achievable in human serum upon conventional therapy. In broth, ampicillin, meropenem, and azithromycin were only bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly bactericidal in a concentration-dependent manner. In cells, ampicillin, meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to 0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU reduction), and gentamicin was virtually inactive. The difference in the efficacies of moxifloxacin and ciprofloxacin in cells did not result from a difference in levels of accumulation in cells (6.96 ± 1.05 versus 7.75 ± 1.03) and was only partially explainable by the difference in the MICs (0.58 ± 0.04 versus 1.40 ± 0.17 mg/liter). Further analysis showed that intracellular moxifloxacin expressed only approximately 1/7 of the activity demonstrated against extracellular bacteria and ciprofloxacin expressed only 1/15 of the activity demonstrated against extracellular bacteria. Gentamicin did not increase the intracellular activities of the other antibiotics tested. The data suggest (i) that moxifloxacin could be of potential interest for eradication of the intracellular forms of
L. monocytogenes
, (ii) that the cellular accumulation of an antibiotic is not the only determinant of its intracellular activity (for fluoroquinolones, it is actually a self-defeating process as far as activity is concerned), and (iii) that pharmacodynamics (activity-to-concentration relationships) need to be considered for the establishment of efficacy against intracellular bacteria, just as they are for the establishment of efficacy against extracellular infections.
CmeABC Functions as a Multidrug Efflux System in
Campylobacter jejuni
Authors: Lin Jun , Michel Linda Overbye , Zhang Qijing
Published: July 2002

Campylobacter jejuni
, a gram-negative organism causing gastroenteritis in humans, is increasingly resistant to antibiotics. However, little is known about the drug efflux mechanisms in this pathogen. Here we characterized an efflux pump encoded by a three-gene operon (designated
cmeABC
) that contributes to multidrug resistance in
C. jejuni
81-176. CmeABC shares significant sequence and structural homology with known tripartite multidrug efflux pumps in other gram-negative bacteria, and it consists of a periplasmic fusion protein (CmeA), an inner membrane efflux transporter belonging to the resistance-nodulation-cell division superfamily (CmeB), and an outer membrane protein (CmeC). Immunoblotting using CmeABC-specific antibodies demonstrated that
cmeABC
was expressed in wild-type 81-176; however, an isogenic mutant (9B6) with a transposon insertion in the
cmeB
gene showed impaired production of CmeB and CmeC. Compared to wild-type 81-176, 9B6 showed a 2- to 4,000-fold decrease in resistance to a range of antibiotics, heavy metals, bile salts, and other antimicrobial agents. Accumulation assays demonstrated that significantly more ethidium bromide and ciprofloxacin accumulated in mutant 9B6 than in wild-type 81-176. Addition of carbonyl cyanide
m
-chlorophenylhydrazone, an efflux pump inhibitor, increased the accumulation of ciprofloxacin in wild-type 81-176 to the level of mutant 9B6. PCR and immunoblotting analysis also showed that
cmeABC
was broadly distributed in various
C. jejuni
isolates and constitutively expressed in wild-type strains. Together, these findings formally establish that CmeABC functions as a tripartite multidrug efflux pump that contributes to the intrinsic resistance of
C. jejuni
to a broad range of structurally unrelated antimicrobial agents.
Resistance to Quinupristin-Dalfopristin Due to Mutation of L22 Ribosomal Protein inStaphylococcus aureus
Authors: Malbruny Brigitte , Canu Annie , Bozdogan Bülent , Fantin Bruno , Zarrouk Virginie , Dutka-Malen Sylvie , Feger Celine , Leclercq Roland
Published: July 2002

The mechanism of resistance to the streptogramin antibiotics quinupristin and dalfopristin was studied in aStaphylococcus aureusclinical isolate selected under quinupristin-dalfopristin therapy, in four derivatives ofS. aureusRN4220 selected in vitro, and in a mutant selected in a model of rabbit aortic endocarditis. For all strains the MICs of erythromycin, quinupristin, and quinupristin-dalfopristin were higher than those for the parental strains but the MICs of dalfopristin and lincomycin were similar. Portions of genes for domains II and V of 23S rRNA and the genes for ribosomal proteins L4 and L22 were amplified and sequenced. All mutants contained insertions or deletions in a protruding β hairpin that is part of the conserved C terminus of the L22 protein and that interacts with 23S rRNA. SusceptibleS. aureusRN4220 was transformed with plasmid DNA encoding the L22 alteration, resulting in transformants that were erythromycin and quinupristin resistant. Synergistic ribosomal binding of streptogramins A and B, studied by analyzing the fluorescence kinetics of pristinamycin IA-ribosome complexes, was abolished in the mutant strain, providing an explanation for quinupristin-dalfopristin resistance.
Acyclovir Cream for Treatment of Herpes Simplex Labialis: Results of Two Randomized, Double-Blind, Vehicle-Controlled, Multicenter Clinical Trials
Authors: Spruance Spotswood L. , Nett Robert , Marbury Thomas , Wolff Ray , Johnson James , Spaulding for The Acyclovir Cream Study Group Theodore
Published: July 2002

Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44;
P
= 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR = 1.24; 95% CI, 1.06 to 1.44;
P
= 0.006). Efficacy was apparent whether therapy was initiated “early” (prodrome or erythema lesion stage) or “late” (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.
Inhibition of Penicillinase by Epigallocatechin Gallate Resulting in Restoration of Antibacterial Activity of Penicillin against Penicillinase-Producing
Staphylococcus aureus
Authors: Zhao Wei-Hua , Hu Zhi-Qing , Hara Yukihiko , Shimamura Tadakatsu
Published: July 2002

The combination of epigallocatechin gallate (EGCg, a main constituent of tea catechins) with penicillin showed synergism against 21 clinical isolates of penicillinase-producing
Staphylococcus aureus
. Besides binding directly to peptidoglycan, the inhibition of penicillinase activity by EGCg is responsible for the synergism. EGCg inhibited the penicillinase activity in a dose-dependent fashion, with a 50% inhibitory concentration of 10 μg/ml.
bla
CTX-M-2
Is Located in an Unusual Class 1 Integron (In35) Which Includes Orf513
Authors: Arduino Sonia M. , Roy Paul H. , Jacoby George A. , Orman Betina E. , Pineiro Silvia A. , Centron Daniela
Published: July 2002

Examination of the
bla
CTX-M-2
gene in plasmid pMAR-12 by sequencing and PCR analysis revealed that the
bla
gene and the surrounding DNA, which is closely related (99% homology) to the
Kluyvera ascorbata
chromosomal DNA that contains the
bla
KLUA-1
gene, are located in a complex
sul1
-type integron, termed In35, that includes Orf513. It is possible that
bla
CTX-M-2
was acquired by plasmid pMAR-12 through an uncharacterized recombinational event in which Orf513 could be involved.
Two Diarylurea Electron Transport Inhibitors Reduce
Staphylococcus aureus
Hemolytic Activity and Protect Cultured Endothelial Cells from Lysis
Authors: Proctor R. A. , Dalal S. C. , Kahl B. , Brar D. , Peters G. , Nichols W. W.
Published: July 2002

Reduction in electron transport is associated with decreased production in alpha-toxin despite the fact that
Staphylococcus aureus
is able to grow from 1 CFU to >10
7
CFU. Similarly, under anaerobic conditions,
S. aureus
does not produce alpha-toxin. Although the pathways that connect oxidative metabolism and toxin production are unknown, agents are available that exhibit greater inhibition of plant versus mammalian electron transport. Herbicides block electron transport in plants by inhibiting the formation of phosphoquinol (QH
2
) in plants. Commercial use in farming is possible because these compounds are much less active against the quinones found mammalian mitochondria. Because bacterial electron transport systems are closer to plant than mammalian systems, we hypothesized that inhibitors of respiration might be able to reduce
S. aureus
electron transport and block the production of alpha-toxin. We studied two compounds and found that the effective dose for the inhibition of bacterial respiration was 50 to >3,500 times lower than the concentration required to cause similar inhibition of rat mitochondrial respiration. Compounds I and II also reduced toxin production in
S. aureus
without causing overt toxicity to cultured endothelial cells. Finally, the compounds reduced the damage caused by
S. aureus
when cocultured with the endothelial cells. This raises the possibility that compounds that inhibit bacterial respiration might be prove valuable for the prevention of toxin production in
S. aureus
.
Steady-State Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Infected Patients with End-Stage Renal Disease Receiving Chronic Dialysis
Authors: Bohjanen Paul R. , Johnson Melissa D. , Szczech Lynda A. , Wray Dannah W. , Petros William P. , Miller Cameron R. , Hicks Charles B.
Published: July 2002

The steady-state pharmacokinetics of lamivudine were evaluated in 11 subjects with human immunodeficiency virus infection and end-stage renal disease, 9 of whom were receiving hemodialysis and 2 of whom were receiving chronic ambulatory peritoneal dialysis (CAPD). All subjects received 150 mg of lamivudine daily for at least 2 weeks prior to sampling for determination of the pharmacokinetics of lamivudine over a 24-h period on 2 consecutive days. On the first day, subjects received 150 mg of oral lamivudine and underwent dialysis (hemodialysis or CAPD). On the second day, subjects received another 150 mg of oral lamivudine but dialysis was not performed. For the subjects undergoing hemodialysis, the geometric mean predose serum lamivudine concentration was 1.14 μg/ml (95% confidence interval [CI], 0.83 to 1.58 μg/ml), the geometric mean maximum concentration in serum (
C
max
) was 3.77 μg/ml (95% CI, 3.01 to 4.71 μg/ml), and the geometric mean area under the serum concentration-time curve from time zero to 24 h (AUC
0-24
) was 49.8 μg · h/ml (95% CI 39.1 to 63.6 μg · h/ml). Hemodialysis removed approximately 28 mg of lamivudine but had no significant effect on
C
max
or AUC
0-24
. In the absence of hemodialysis, the geometric mean lamivudine terminal elimination half-life was 17.2 h (95% CI, 10.5 to 28.1 h), whereas the geometric mean intradialysis half-life of lamivudine was 5.3 h (95% CI, 3.4 to 8.2 h). The pharmacokinetics of lamivudine in subjects undergoing CAPD were similar to those in subjects undergoing hemodialysis. CAPD removed 24 mg of lamivudine over a 24-h period but had no effect on
C
max
or AUC
0-24
. Pharmacokinetic modeling suggests that a lamivudine dose of 25 mg daily in hemodialysis subjects would provide serum exposure similar to that provided by a dose of 150 mg twice daily in patients with normal renal function.