bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical and optical characteristics of etch induced damage in InGaAs
Authors: Berg E. W. , Pang S. W.
Published: July 2002

The effects of etch induced damage on the electrical and optical properties of AlGaAs/InGaAs quantum wells (QWs) were studied. From the variations in the photoluminescence (PL) intensity and the conductivity of etched gratings, the optical cutoff width was found to be 33 nm whereas the electrical cutoff width was 136 nm. The PL intensity of the gratings indicated that increased stage power during etching causes more damage. Comparisons were also made between the sheet resistivity (ρs) of transmission lines and the conductivity of wires after etching of AlGaAs/InGaAs and AlInAs/InGaAs QWs grown on GaAs and InP substrates, respectively. The AlGaAs/InGaAs QW transmission lines showed reduced ρs after etching with higher stage power, although the ρs was still higher than that of the unetched control sample. The AlInAs/InGaAs QW transmission lines had a higher ρs as the stage power was increased. The two material systems also showed different etch time and sidewall damage characteristics. The AlInAs/InGaAs QW structure degraded more severely at a shorter etch time and had a larger cutoff width as extracted from etched conducting wires.
Effect of nitrogen incorporation on electron emission from chemical vapor deposited diamond
Authors: Park M. , Sowers A. T. , Rinne C. Lizzul , Schlesser R. , Bergman L. , Nemanich R. J. , Sitar Z. , Hren J. J. , Cuomo J. J. , Zhirnov V. V. , Choi W. B.
Published: July 2002

Two different types of the nitrogen-doped chemical vapor deposited (CVD) diamond films were synthesized with N2 (nitrogen) and C3H6N6 (melamine) as doping sources. The samples were analyzed by scanning electron microscopy, Raman scattering, photoluminescence spectroscopy, and field-emission measurements. More effective substitutional nitrogen doping was achieved with C3H6N6 than with N2. The diamond film doped with N2 contained a significant amount of nondiamond carbon phases. The sample produced with N2 exhibited a lower field emission turn-on field than the sample produced with C3H6N6. It is believed that the presence of the graphitic phases (or amorphous sp2 carbon) at the grain boundaries of the diamond and/or the nanocrystallinity (or microcrystallinity) of the diamond play a significant role in lowering the turn-on field of the film produced using N2. It is speculated that substitutional nitrogen doping plays only a minor role in changing the field emission characteristics of CVD diamond films.
Effect of in situ plasma oxidation of TiN diffusion barrier for AlSiCu/TiN/Ti metallization structure of integrated circuits
Authors: Fortin V. , Gujrathi S. C. , Gagnon G. , Gauvin R. , Currie J. F. , Ouellet L. , Tremblay Y.
Published: July 2002

An oxygen plasma treatment of the TiN diffusion barrier prior to Al deposition of an AlSiCu/TiN/Ti structure is studied and compared to an air break process in order to determine the reactions occurring at the Al/TiN interface as well as the mechanisms responsible for the improved barrier performance using an ex situ and an in situ oxygen plasma, respectively. Various experimental techniques such as grazing angle x-ray diffraction, elastic recoil detection and field emission scanning electron microscopy were used. The ternary and quaternary phase diagrams were used to predict the phases formed. It is first observed that an oxygen plasma increases the oxygen concentration at the Al/TiN interface as well as in the TiN barrier. It is conjectured that first the oxygen reacts with Ti in order to form Ti oxides in the TiN grain boundaries and on the TiN surface. The Al film then reacts with this Ti oxide layer in order to form an Al2O3 layer upon sintering which in turn acts as an additional diffusion barrier at the Al/TiN interface. It is also determined that the Al2O3 phase formation is increased after an oxygen plasma treatment of the TiN diffusion barrier. This Al oxide layer as well as the Ti oxides in the TiN grain boundaries could reduce the Al and Ti intermixing as observed by the reduction in the formation of TiAl3. The reduced Al diffusion in the barrier would then stop Si outdiffusion from the substrate. In addition, the penetration of Si would also be blocked at the Al/TiN interface by the Al2O3 layer. The decreased Si penetration in the upper layers in addition to the lower TiAl3 formation are the mechanisms proposed to explain the decreased formation of Ti7Al5Si12 after an in situ oxygen plasma treatment of the TiN diffusion barrier. It is concluded that an oxygen plasma-treated TiN barrier is more efficient than an air-exposed TiN one due to the lower degree of Ti7Al5Si12 formation which also explains the reduced risks of junction spiking. The advantage of the in situ oxygen plasma treatment is therefore related to better process control in addition to higher throughput.
Collapse behavior of microresist pattern analyzed by the tip indentation method with an atomic force microscope
Authors: Kawai Akira
Published: July 2002

A novel method for quantitative analysis of the adhesion property of a resist micropattern is demonstrated experimentally. By applying a normal load directly with a microcantilever tip, a photoresist micropattern adhering to a substrate can be collapsed easily. The load, when the pattern collapse occurred, increased with the heating temperature of the resist pattern. The detectable sensitivity of this method can be estimated as less than 0.1 nN. The validity and reliability of this method are discussed by comparing with the adhesion result of the conventional peeling test.
Microstructure and electrical properties of Sb nanocrystals formed in thin, thermally grown SiO2 layers by low-energy ion implantation
Authors: Nakajima Anri , Nakao Hiroshi , Ueno Hiroaki , Futatsugi Toshiro , Yokoyama Naoki
Published: July 2002

We have formed Sb nanocrystals in thin, thermally grown SiO2 layers using low-energy ion implantation which was followed by thermal annealing. These Sb nanocrystals showed good uniformity with respect to size and position. Both the narrow as-implanted profile and the compressive strain that exists near the SiO2/Si interface are considered to contribute to the uniformity. We found that it was possible to control the size of the Sb nanocrystal by changing the dose of the implanted Sb. The I–V characteristics of the diodes which had Sb nanocrystals with an average diameter of 3.3 nm showed good reproducibility. Moreover, these diodes showed a Coulomb blockade region around 0 V and a Coulomb staircase at 4.2 K. Identical I–V characteristics were obtained for all the samples measured, indicating an excellent reproducibility. Almost the same Coulomb blockade region as that at 4.2 K was observed up to a temperature as high as 100 K even for a diode which had larger Sb nanocrystals (with an average diameter of 5.6 nm). The technique introduced here offers the possibility of developing practical Si-based single-electron devices.
New developments for shallow depth profiling with the Cameca IMS 6f
Authors: Schuhmacher M. , Rasser B. , Desse F.
Published: July 2002

A new ion optical system has been developed for the duoplasmatron source of the Cameca IMS 6f instrument. This system improves performance at low impact energies. It consists of a new primary ion extraction system operating in acceleration/deceleration mode and an additional lens. It provides better source emittance matching with the primary column acceptance and a minimization of the space charge effect in the source plasma. The primary beam density in the sub-kilo-electron-volt impact energy range (down to 500 eV) is therefore improved. This article describes the new extraction system, the performance improvements are discussed in terms of beam intensity and density as a function of impact energy, and application examples for B and P shallow profiles are provided. Results demonstrating the benefits of the sample rotation technique for B depth profiling in silicon with low impact energy O2+ beam and oxygen flooding are also presented.
Three-Dimensionally Ordered Array of Air Bubbles in a Polymer Film
Authors: Srinivasarao Mohan , Collings David , Philips Alan , Patel Sanjay
Published: July 2002

We report the formation of a three-dimensionally ordered array of air bubbles of monodisperse pore size in a polymer film through a templating mechanism based on thermocapillary convection. Dilute solutions of a simple, coil-like polymer in a volatile solvent are cast on a glass slide in the presence of moist air flowing across the surface. Evaporative cooling and the generation of an ordered array of breath figures leads to the formation of multilayers of hexagonally packed water droplets that are preserved in the final, solid polymer film as spherical air bubbles. The dimensions of these bubbles can be controlled simply by changing the velocity of the airflow across the surface. When these three-dimensionally ordered macroporous materials have pore dimensions comparable to the wavelength of visible light, they are of interest as photonic band gaps and optical stop-bands.
Simultaneous Rupture Along Two Conjugate Planes of the Wharton Basin Earthquake
Authors: Robinson D. P. , Henry C. , Das S. , Woodhouse J. H.
Published: July 2002

Analysis of broadband teleseismic data shows that the 18 June 2000 Wharton Basin earthquake, a moment magnitude 7.8 intraplate event in the region of diffuse deformation separating the Indian and Australian plates, consisted of two subevents that simultaneously ruptured two near-conjugate planes. This mode of rupture accommodates shortening by a mechanism different from that previously known elsewhere in the region. The larger subevent occurred on a fossil fracture zone, with a relatively high stress drop of about 20 megapascals, showing that large stresses can accumulate in regions of distributed deformation.
Protective Role of ATP-Sensitive Potassium Channels in Hypoxia-Induced Generalized Seizure
Authors: Yamada Katsuya , Ji Juan Juan , Yuan Hongjie , Miki Takashi , Sato Shinichi , Horimoto Naoki , Shimizu Tetsuo , Seino Susumu , Inagaki Nobuya
Published: July 2002

Adenosine triphosphate (ATP)–sensitive potassium (K
ATP
) channels are activated by various metabolic stresses, including hypoxia. The substantia nigra pars reticulata (SNr), the area with the highest expression of K
ATP
channels in the brain, plays a pivotal role in the control of seizures. Mutant mice lacking the Kir6.2 subunit of K
ATP
channels [knockout (KO) mice] were susceptible to generalized seizures after brief hypoxia. In normal mice, SNr neuron activity was inactivated during hypoxia by the opening of the postsynaptic K
ATP
channels, whereas in KO mice, the activity of these neurons was enhanced. K
ATP
channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures.
Observation of Covalent Intermediates in an Enzyme Mechanism at Atomic Resolution
Authors: Heine Andreas , DeSantis Grace , Luz John G. , Mitchell Michael , Wong Chi-Huey , Wilson Ian A.
Published: July 2002

In classical enzymology, intermediates and transition states in a catalytic mechanism are usually inferred from a series of biochemical experiments. Here, we derive an enzyme mechanism from true atomic-resolution x-ray structures of reaction intermediates. Two ultra–high resolution structures of wild-type and mutant
d
-2-deoxyribose-5-phosphate (DRP) aldolase complexes with DRP at 1.05 and 1.10 angstroms unambiguously identify the postulated covalent carbinolamine and Schiff base intermediates in the aldolase mechanism. In combination with site-directed mutagenesis and
1
H nuclear magnetic resonance, we can now propose how the heretofore elusive C-2 proton abstraction step and the overall stereochemical course are accomplished. A proton relay system appears to activate a conserved active-site water that functions as the critical mediator for proton transfer.
Regional
14
CO
2
Offsets in the Troposphere: Magnitude, Mechanisms, and Consequences
Authors: Kromer Bernd , Manning Sturt W. , Kuniholm Peter Ian , Newton Maryanne W. , Spurk Marco , Levin Ingeborg
Published: July 2002

Radiocarbon dating methods typically assume that there are no significant tropospheric
14
CO
2
gradients within the low- to mid-latitude zone of the Northern Hemisphere. Comparison of tree ring
14
C data from southern Germany and Anatolia supports this assumption in general but also documents episodes of significant short-term regional
14
CO
2
offsets. We suggest that the offset is caused by an enhanced seasonal
14
CO
2
cycle, with seasonally peaked flux of stratospheric
14
C into the troposphere during periods of low solar magnetic activity, coinciding with substantial atmospheric cooling. Short-term episodes of regional
14
CO
2
offsets are important to palaeoclimate studies and to high-resolution archaeological dating.
Exchange of Protein Molecules Through Connections Between Higher Plant Plastids
Authors: Köhler Rainer H. , Cao Jun , Zipfel Warren R. , Webb Watt W. , Hanson Maureen R.
Published: July 2002

Individual plastids of vascular plants have generally been considered to be discrete autonomous entities that do not directly communicate with each other. However, in transgenic plants in which the plastid stroma was labeled with green fluorescent protein (GFP), thin tubular projections emanated from individual plastids and sometimes connected to other plastids. Flow of GFP between interconnected plastids could be observed when a single plastid or an interconnecting plastid tubule was photobleached and the loss of green fluorescence by both plastids was seen. These tubules allow the exchange of molecules within an interplastid communication system, which may facilitate the coordination of plastid activities.
Interaction Between the ENSO and the Asian Monsoon in a Coral Record of Tropical Climate
Authors: Charles C. D. , Hunter D. E. , Fairbanks Richard G.
Published: July 2002

The oxygen isotopic composition of a banded coral from the western equatorial Indian Ocean provides a 150-year-long history of the relation between the El Niño–Southern Oscillation (ENSO) phenomenon and the Asian monsoon. Interannual cycles in the coral time series were found to correlate with Pacific coral and instrumental climate records, suggesting a consistent linkage across ocean basins, despite the changing frequency and amplitude of the ENSO. However, decadal variability that is characteristic of the monsoon system also dominates the coral record, which implies important interactions between tropical and midlatitude climate variability. One prominent manifestation of this interaction is the strong amplitude modulation of the quasi-biennial cycle.
Two-Dimensional Melting of an Anisotropic Crystal Observed at the Molecular Level
Authors: Sikes H. D. , Schwartz D. K.
Published: July 2002

A distinctive two-dimensional (2D) melting transition occurring at nearly 100 degrees Celsius (°C) has been observed in Langmuir-Blodgett films by in situ atomic force microscopy (AFM). A 2D orthorhombic crystal phase melted to a 2D smectic phase at about 91°C. The smectic phase was characterized by 1D molecular periodicity with short-range correlations (about 40 angstroms). At 95°C, the smectic order melted to form a hexatic phase. Infrared spectroscopy measurements were consistent with the AFM observations. These observations support the dislocation-mediated melting scenario for an anisotropic 2D crystal predicted by Ostlund and Halperin. A longer wavelength height modulation was also observed in the smectic and hexatic phases.
Stable Isotope Enrichment in Stratospheric Nitrous Oxide
Authors: Rahn Thom , Wahlen Martin
Published: July 2002

Nitrous oxide is a greenhouse gas that also plays a role in the cycling of stratospheric ozone. Air samples from the lower stratosphere exhibit
15
N/
14
N and
18
O/
16
O enrichment in nitrous oxide, which can be accounted for with a simple model describing an irreversible destruction process. The observed enrichments are quite large and incompatible with those determined for the main stratospheric nitrous oxide loss processes of photolysis and reaction with excited atomic oxygen. Thus, although no stratospheric source needs to be invoked, the data indicate that present understanding of stratospheric nitrous oxide chemistry is incomplete.
Role of Substrates and Products of PI 3-kinase in Regulating Activation of Rac-Related Guanosine Triphosphatases by Vav
Authors: Han Jaewon , Luby-Phelps Katherine , Das Balaka , Shu Xiaodong , Xia Yi , Mosteller Raymond D. , Krishna U. Murali , Falck John R. , White Michael A. , Broek Daniel
Published: July 2002

Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)–guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.
Plasma Insulin-Like Growth Factor-I and Prostate Cancer Risk: A Prospective Study
Authors: Chan June M. , Stampfer Meir J. , Giovannucci Edward , Gann Peter H. , Ma Jing , Wilkinson Peter , Hennekens Charles H. , Pollak Michael
Published: July 2002

Insulin-like growth factor–I (IGF-I) is a mitogen for prostate epithelial cells. To investigate associations between plasma IGF levels and prostate cancer risk, a nested case-control study within the Physicians' Health Study was conducted on prospectively collected plasma from 152 cases and 152 controls. A strong positive association was observed between IGF-I levels and prostate cancer risk. Men in the highest quartile of IGF-I levels had a relative risk of 4.3 (95 percent confidence interval 1.8 to 10.6) compared with men in the lowest quartile. This association was independent of baseline prostate-specific antigen levels. Identification of plasma IGF-I as a predictor of prostate cancer risk may have implications for risk reduction and treatment.
Rad53 FHA Domain Associated with Phosphorylated Rad9 in the DNA Damage Checkpoint
Authors: Sun Zhaoxia , Hsiao James , Fay David S. , Stern David F.
Published: July 2002

The Rad53 protein kinase of
Saccharomyces cerevisiae
is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology–associated (FHA) domain of Rad53. Inactivation of this domain abolished DNA damage–dependent Rad53 phosphorylation, G
2
/M cell cycle phase arrest, and increase of
RNR3
transcription but did not affect replication inhibition–dependent Rad53 phosphorylation. Thus, Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The hitherto uncharacterized FHA domain appears to be a modular protein-binding domain.
A Correlation Between Ultra-Low Basal Velocities in the Mantle and Hot Spots
Authors: Williams Q. , Revenaugh J. , Garnero E.
Published: July 2002

The statistical correlation between the locations of hot spots at the surface of Earth and the distribution of ultra-low-velocity zones at the base of the mantle has about a 1 percent chance of arising randomly. This correlation is more significant than that between hot spots and negative velocity anomalies in tomographic models of deep mantle compressional and shear velocity. This correlation is consistent with the notion that many hot spots originate in a low-velocity, probably partially molten layer at the core-mantle boundary and undergo little lateral deflection on ascent.
Exceeding 5000-Fold Concentration of Dilute Analytes in Micellar Electrokinetic Chromatography
Authors: Quirino Joselito P. , Terabe Shigeru
Published: July 2002

When a neutral analyte zone is injected into a charged pseudostationary phase, the length of the zone is predicted to be narrowed by 1/(1 +
k
), where
k
is the retention factor. The conditions for zone narrowing to occur assume negligible electroosmotic flow, a relatively constant electric field along the capillary column, and no pseudostationary phase in the injected analyte mixture. The theoretically expected concentration enhancement was demonstrated experimentally. Consequently, the detection sensitivity of analytes in micellar electrokinetic chromatography (MEKC) can be improved significantly. For example, 9 to 18 parts per billion of an environmentally important racemic herbicide spiked in lake water was separated by MEKC and detected by ultraviolet absorption.
Phosphorylation and Activation of 13
S
Condensin by Cdc2 in Vitro
Authors: Kimura Keiji , Hirano Michiko , Kobayashi Ryuji , Hirano Tatsuya
Published: July 2002

13
S
condensin is a multisubunit protein complex essential for mitotic chromosome condensation in
Xenopus
egg extracts. Purified 13
S
condensin introduces positive supercoils into DNA in the presence of topoisomerase I and adenosine triphosphate in vitro. The supercoiling activity of 13
S
condensin was regulated by mitosis-specific phosphorylation. Immunodepletion, in vitro phosphorylation, and peptide-mapping experiments indicated that Cdc2 is likely to be the kinase that phosphorylates and activates 13
S
condensin. Multiple Cdc2 phosphorylation sites are clustered in the carboxyl-terminal domain of the XCAP-D2 (
Xenopus
chromosome-associated polypeptide D2) subunit. These results suggest that phosphorylation of 13
S
condensin by Cdc2 may trigger mitotic chromosome condensation in vitro.
Compositional Heterogeneity in the Bottom 1000 Kilometers of Earth's Mantle: Toward a Hybrid Convection Model
Authors: van der Hilst Rob D. , Kárason Hrafnkell
Published: July 2002

Tomographic imaging indicates that slabs of subducted lithosphere can sink deep into Earth's lower mantle. The view that convective flow is stratified at 660-kilometer depth and preserves a relatively pristine lower mantle is therefore not tenable. However, a range of geophysical evidence indicates that compositionally distinct, hence convectively isolated, mantle domains may exist in the bottom 1000 kilometers of the mantle. Survival of these domains, which are perhaps related to local iron enrichment and silicate-to-oxide transformations, implies that mantle convection is more complex than envisaged by conventional end-member flow models.
Dynamic Control of CaMKII Translocation and Localization in Hippocampal Neurons by NMDA Receptor Stimulation
Authors: Shen Kang , Meyer Tobias
Published: July 2002

Calcium-calmodulin–dependent protein kinase II (CaMKII) is thought to increase synaptic strength by phosphorylating postsynaptic density (PSD) ion channels and signaling proteins. It is shown that
N
-methyl-
D
-aspartate (NMDA) receptor stimulation reversibly translocates green fluorescent protein–tagged CaMKII from an F-actin–bound to a PSD-bound state. The translocation time was controlled by the ratio of expressed β-CaMKII to α-CaMKII isoforms. Although F-actin dissociation into the cytosol required autophosphorylation of or calcium-calmodulin binding to β-CaMKII, PSD translocation required binding of calcium-calmodulin to either the α- or β-CaMKII subunits. Autophosphorylation of CaMKII indirectly prolongs its PSD localization by increasing the calmodulin-binding affinity.
65,000 Years of Vegetation Change in Central Australia and the Australian Summer Monsoon
Authors: Johnson B. J. , Miller G. H. , Fogel M. L. , Magee J. W. , Gagan M. K. , Chivas A. R.
Published: July 2002

Carbon isotopes in fossil emu (
Dromaius novaehollandiae
) eggshell from Lake Eyre, South Australia, demonstrate that the relative abundance of C
4
grasses varied substantially during the past 65,000 years. Currently, C
4
grasses are more abundant in regions that are increasingly affected by warm-season precipitation. Thus, an expansion of C
4
grasses likely reflects an increase in the relative effectiveness of the Australian summer monsoon, which controls summer precipitation over Lake Eyre. The data imply that the Australian monsoon was most effective between 45,000 and 65,000 years ago, least effective during the Last Glacial Maximum, and moderately effective during the Holocene.
The Cavity and Pore Helices in the KcsA K
+
Channel: Electrostatic Stabilization of Monovalent Cations
Authors: Roux Benoı̂t , MacKinnon Roderick
Published: July 2002

The electrostatic influence of the central cavity and pore alpha helices in the potassium ion channel from
Streptomyces lividans
(KcsA K
+
channel) was analyzed by solving the finite difference Poisson equation. The cavity and helices overcome the destabilizing influence of the membrane and stabilize a cation at the membrane center. The electrostatic effect of the pore helices is large compared to that described for water-soluble proteins because of the low dielectric membrane environment. The combined contributions of the ion self-energy and the helix electrostatic field give rise to selectivity for monovalent cations in the water-filled cavity. Thus, the K
+
channel uses simple electrostatic principles to solve the fundamental problem of ion destabilization by the cell membrane lipid bilayer.
Cortical Mechanisms of Human Imitation
Authors: Iacoboni Marco , Woods Roger P. , Brass Marcel , Bekkering Harold , Mazziotta John C. , Rizzolatti Giacomo
Published: July 2002

How does imitation occur? How can the motor plans necessary for imitating an action derive from the observation of that action? Imitation may be based on a mechanism directly matching the observed action onto an internal motor representation of that action (“direct matching hypothesis”). To test this hypothesis, normal human participants were asked to observe and imitate a finger movement and to perform the same movement after spatial or symbolic cues. Brain activity was measured with functional magnetic resonance imaging. If the direct matching hypothesis is correct, there should be areas that become active during finger movement, regardless of how it is evoked, and their activation should increase when the same movement is elicited by the observation of an identical movement made by another individual. Two areas with these properties were found in the left inferior frontal cortex (opercular region) and the rostral-most region of the right superior parietal lobule.
Tropical Pacific Forcing of Decadal SST Variability in the Western Indian Ocean over the Past Two Centuries
Authors: Cole Julia E. , Dunbar Robert B. , McClanahan Timothy R. , Muthiga Nyawira A.
Published: July 2002

A 194-year annual record of skeletal δ
18
O from a coral growing at Malindi, Kenya, preserves a history of sea surface temperature (SST) change that is coherent with instrumental and proxy records of tropical Pacific climate variability over interannual to decadal periods. This variability is superimposed on a warming of as much as 1.3°C since the early 1800s. These results suggest that the tropical Pacific imparts substantial decadal climate variability to the western Indian Ocean and, by implication, may force decadal variability in other regions with strong El Niño–Southern Oscillation teleconnections.
Multidecadal Changes in the Vertical Temperature Structure of the Tropical Troposphere
Authors: Gaffen Dian J. , Santer Benjamin D. , Boyle James S. , Christy John R. , Graham Nicholas E. , Ross Rebecca J.
Published: July 2002

Trends in global lower tropospheric temperature derived from satellite observations since 1979 show less warming than trends based on surface meteorological observations. Independent radiosonde observations of surface and tropospheric temperatures confirm that, since 1979, there has been greater warming at the surface than aloft in the tropics. Associated lapse-rate changes show a decrease in the static stability of the atmosphere, which exceeds unforced static stability variations in climate simulations with state-of-the-art coupled ocean-atmosphere models. The differential temperature trends and lapse-rate changes seen during the satellite era are not sustained back to 1960.
A Potassium Channel Protein Encoded by Chlorella Virus PBCV-1
Authors: Plugge B. , Gazzarrini S. , Nelson M. , Cerana R. , Van J. L. , Etten  , Derst C. , DiFrancesco D. , Moroni A. , Thiel G.
Published: July 2002

The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in
Xenopus laevis
oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.
Cloning of the
Arabidopsis
Clock Gene
TOC1
, an Autoregulatory Response Regulator Homolog
Authors: Strayer Carl , Oyama Tokitaka , Schultz Thomas F. , Raman Ramanujam , Somers David E. , Más Paloma , Panda Satchidananda , Kreps Joel A. , Kay Steve A.
Published: July 2002

The
toc1
mutation causes shortened circadian rhythms in light-grown
Arabidopsis
plants. Here, we report the same
toc1
effect in the absence of light input to the clock. We also show that
TOC1
controls photoperiodic flowering response through clock function. The
TOC1
gene was isolated and found to encode a nuclear protein containing an atypical response regulator receiver domain and two motifs that suggest a role in transcriptional regulation: a basic motif conserved within the
CONSTANS
family of transcription factors and an acidic domain.
TOC1
is itself circadianly regulated and participates in a feedback loop to control its own expression.
Chemical Etiology of Nucleic Acid Structure: The α-Threofuranosyl-(3'→2') Oligonucleotide System
Authors: Schöning K.-U. , Scholz P. , Guntha S. , Wu X. , Krishnamurthy R. , Eschenmoser A.
Published: July 2002

TNAs [(
l
)-α-threofuranosyl oligonucleotides] containing vicinally connected (3′→2′) phosphodiester bridges undergo informational base pairing in antiparallel strand orientation and are capable of cross-pairing with RNA and DNA. Being derived from a sugar containing only four carbons, TNA is structurally the simplest of all potentially natural oligonucleotide-type nucleic acid alternatives studied thus far. This, along with the base-pairing properties of TNA, warrants close scrutiny of the system in the context of the problem of RNA's origin.
Gamma Oscillations and Object Processing in the Infant Brain
Authors: Csibra G. , Davis G. , Spratling M. W. , Johnson M. H.
Published: July 2002

An enduring controversy in neuroscience concerns how the brain “binds” together separately coded stimulus features to form unitary representations of objects. Recent evidence has indicated a close link between this binding process and 40-hertz (gamma-band) oscillations generated by localized neural circuits. In a separate line of research, the ability of young infants to perceive objects as unitary and bounded has become a central focus for debates about the mechanisms of perceptual development. Here we demonstrate that binding-related 40-hertz oscillations are evident in the infant brain around 8 months of age, which is the same age at which behavioral and event-related potential evidence indicates the onset of perceptual binding of spatially separated static visual features.
Evolving Genomic Metaphors: A New Look at the Language of DNA
Authors: Avise John C.
Published: July 2002

Recent genome-sequencing efforts have confirmed that traditional “good-citizen” genes (those that encode functional RNA and protein molecules of obvious benefit to the organism) constitute only a small fraction of the genomic populace in humans and other multicellular creatures. The rest of the DNA sequence includes an astonishing collection of noncoding regions, regulatory modules, deadbeat pseudogenes, legions of repetitive elements, and hosts of oft-shifty, self-interested nomads, renegades, and immigrants. To help visualize functional operations in such intracellular genomic societies and to better encapsulate the evolutionary origins of complex genomes, new and evocative metaphors may be both entertaining and research-stimulating.
Comparative Pharmacokinetics, Tissue Distributions, and Effects on Renal Function of Novel Polymeric Formulations of Amphotericin B and Amphotericin B-Deoxycholate in Rats
Authors: Echevarría Iciar , Barturen Celia , Renedo María Jesús , Trocóniz Iñaki F. , Dios-Viéitez M. Carmen
Published: July 2002

The pharmacokinetic profiles of a traditional formulation of amphotericin B (Fungizone) and novel nanosphere and mixed micelle delivery systems developed for amphotericin B were compared and described. Six groups of male Wistar rats received intravenous injections of the different formulations. Plasma and tissue samples were obtained at 11 different times after dosing, with three animals used each time. The amphotericin B concentrations in plasma and tissues were analyzed by high-performance liquid chromatography. The plasma drug concentration-time profiles were best described by a two-compartment model. Models that described the observed single or double peak disposition kinetics in kidney, liver, and spleen were also developed. Parameter estimates from those models show that components of the formulation such as poloxamer 188, which is present in all new formulations, seem to play an important role in the rate of drug uptake by the tissues; in general, the levels of amphotericin B in tissues were increased after the administration of the new formulations compared with those after the administration of Fungizone. The increment in the baseline plasma creatinine level was used as an index of renal function. All formulations increased this baseline value, but the novel formulations exhibited fewer renal effects than Fungizone did. However, a direct relationship between drug exposure in the kidneys and development of renal damage could not be found.
Clarithromycin Inhibits NF-κB Activation in Human Peripheral Blood Mononuclear Cells and Pulmonary Epithelial Cells
Authors: Ichiyama Takashi , Nishikawa Miki , Yoshitomi Tomomi , Hasegawa Shunji , Matsubara Tomoyo , Hayashi Takashi , Furukawa Susumu
Published: July 2002

Macrolide antibiotics modulate the production of proinflammatory cytokines in vivo and in vitro. Transcription of the genes for these proinflammatory cytokines is regulated by nuclear factor κB (NF-κB). We examined whether or not clarithromycin inhibits the activation of NF-κB induced by tumor necrosis factor alpha (TNF-α) or staphylococcal enterotoxin A (SEA) in human monocytic U-937 cells, a T-cell line (Jurkat), a pulmonary epithelial cell line (A549), and peripheral blood mononuclear cells (PBMC). Flow cytometry revealed that clarithromycin suppresses NF-κB activation induced by TNF-α in U-937 and Jurkat cells in a concentration-related manner. Western blot analysis also demonstrated that clarithromycin inhibits NF-κB activation induced by TNF-α in U-937, Jurkat, and A549 cells and PBMC and by SEA in PBMC. Western blot analysis of cytoplasmic extracts of A549 cells revealed that this inhibition is not linked to preservation of expression of the IκBα protein. The chloramphenicol acetyltransferase assay indicated that NF-κB-dependent reporter gene expression is suppressed in U-937 cells pretreated with clarithromycin. These findings are consistent with the idea that clarithromycin suppresses the production of proinflammatory cytokines via inhibition of NF-κB activation.
Aminoglycoside Resistance Genes
aph(2")-Ib
and
aac(6′)-Im
Detected Together in Strains of both
Escherichia coli
and
Enterococcus faecium
Authors: Chow Joseph W. , Kak Vivek , You Il , Kao Susan J. , Petrin Joanne , Clewell Don B. , Lerner Stephen A. , Miller George H. , Shaw Karen J.
Published: July 2002

Escherichia coli
SCH92111602 expresses an aminoglycoside resistance profile similar to that conferred by the
aac(6′)-Ie-aph(2")-Ia
gene found in gram-positive cocci and was found to contain the aminoglycoside resistance genes
aph(2")-Ib
and
aac(6′)-Im
(only 44 nucleotides apart).
aph(2")-Ib
had been reported previously in
Enterococcus faecium
SF11770.
aac(6′)-Im
had not been detected previously in enterococci and was found to be present also 44 nucleotides downstream from
aph(2")-Ib
in
E. faecium
SF11770.
aph(2")-Ib
and
aac(6′)-Im
are separate open reading frames, each with its own putative ribosome binding site, whereas
aac(6′)-Ie-aph(2")-Ia
appears to be a fusion of two genes with just one start and one stop codon. The deduced AAC(6′)-Im protein exhibits 56% identity and 80% similarity to the AAC(6′)-Ie domain of the bifunctional enzyme AAC(6′)-APH(2"). Our results document the existence of a member of the
aph(2")
family of genes in gram-negative bacteria and provide evidence suggesting the horizontal transfer of
aph(2")-Ib
and
aac(6′)-Im
as a unit between gram-positive and gram-negative bacteria.
Antioxidant Functions Required for Insusceptibility of
Saccharomyces cerevisiae
to Tetracycline Antibiotics
Authors: Angrave Fiona E. , Avery Simon V.
Published: July 2002

Cu,Zn superoxide dismutase (Sod1) is required for insusceptibility of
Saccharomyces cerevisiae
to oxytetracycline (OTC). Here we report that Sod1 is also required for insusceptibility to doxycycline (DOX). Furthermore, among a range of antioxidant and redox balance mutants,
mac1
and
ctr1
deletion strains exhibited marked sensitization to OTC and DOX. Certain mutants exhibited a slight sensitivity to methacycline and minocycline. Addition of copper suppressed antibiotic sensitivity. Thus, intracellular copper as well as superoxide dismutase can be critical for eukaryotic tolerance of several tetracycline antibiotics.
Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis
Authors: Montgomery Megan J. , Beringer Paul M. , Aminimanizani Amir , Louie Stan G. , Shapiro Bertrand J. , Jelliffe Roger , Gill Mark A.
Published: July 2002

Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC
0–24
)/MIC ratio of ≥125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for
Pseudomonas aeruginosa
were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC
0–24
/MIC ratio of ≥125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at α phase, 0.16 h; and half-life at β phase, 2.9 h. The overall fractional attainment of achieving an AUC
0–24
/MIC ratio of ≥125 against
P. aeruginosa
isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 μg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC
0–24
/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC
0–24
/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients.
Antileishmanial Activity of an Indole Alkaloid fromPeschiera australis
Authors: Delorenzi Jan Carlo , Attias Márcia , Gattass Cerli R. , Andrade Marcelo , Rezende Cláudia , da Cunha Pinto Ângelo , Henriques Amélia T. , Bou-Habib Dumith C. , Saraiva Elvira M. B.
Published: July 2002

In this study, we show the leishmanicidal effects of a chloroform fraction (CLF) and a purified indole alkaloid obtained from crude stem extract ofPeschiera australisagainstLeishmania amazonensis, a causative agent of cutaneous leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the leishmanicidal activity in CLF completely and irreversibly inhibited promastigote growth. This fraction was also active against amastigotes in infected murine macrophages. Chemical analysis of CLF identified an iboga-type indole alkaloid coronaridine as one of its major compounds. Coronaridine showed potent antileishmanial activity, inhibiting promastigote and amastigote growth. Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced alterations in their mitochondria as assessed by transmission electron microscopy.
Antimicrobial Resistance among Clinical Isolates of
Streptococcus pneumoniae
in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995
Authors: Doern Gary V. , Heilmann Kristopher P. , Huynh Holly K. , Rhomberg Paul R. , Coffman Stacy L. , Brueggemann Angela B.
Published: July 2002

A total of 1,531 recent clinical isolates of
Streptococcus pneumoniae
were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of
S. pneumoniae
were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC
90
s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC
90
of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of
S. pneumoniae
; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with
S. pneumoniae
have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with
S. pneumoniae
continues to increase in the United States.
In Vitro Activities of Antibiotics against
Plasmodium falciparum
Are Inhibited by Iron
Authors: Pradines Bruno , Rogier Christophe , Fusai Thierry , Mosnier Joel , Daries William , Barret Eric , Parzy Daniel
Published: July 2002

The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated on
Plasmodium falciparum
clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro activity against
P. falciparum
, which increased after a prolonged exposure (96 or 144 h). In the presence of iron (FeCl
3
), only the activities of tetracyclines and norfloxacin were decreased. Their in vitro activity against intraerythrocytic stages of multidrug-resistant
P. falciparum
and their efficacy in vivo favor the use of antibiotics as antimalarial drugs. However, due to their slow antimalarial action and to the fact that they act better after prolonged contact, they probably need to be administered in conjunction with a rapidly acting antimalarial drug, such as a short course of chloroquine or quinine.
Molecular Characterization of a Novel Plasmid-Encoded Cefotaximase (CTX-M-12) Found in Clinical
Klebsiella pneumoniae
Isolates from Kenya
Authors: Kariuki S. , Corkill J. E. , Revathi G. , Musoke R. , Hart C. A.
Published: July 2002

Nine
Klebsiella pneumoniae
isolates, six from blood and three from cerebrospinal fluid of newborn babies at Kenyatta National Hospital, Nairobi, Kenya, were analyzed for the mechanism of cephalosporin resistance. By using pulsed-field gel electrophoresis of
Xba
I-digested chromosomal DNA, all the nine isolates were found to be clonal. PCR and direct sequencing revealed a novel extended-spectrum β-lactamase, which we designated CTX-M-12. It has a more potent hydrolytic activity against cefotaxime than against ceftazidime and a pI of 9.0 and is encoded on a large self-transferable ca. 160-kbp plasmid.
Resistance to Linezolid: Characterization of Mutations in rRNA and Comparison of Their Occurrences in Vancomycin-Resistant Enterococci
Authors: Prystowsky Jason , Siddiqui Farida , Chosay John , Shinabarger Dean L. , Millichap John , Peterson Lance R. , Noskin Gary A.
Published: July 2002

To assess the potential for emergence of resistance during the use of linezolid, we tested 10 clinical isolates of vancomycin-resistant enterococci (VRE) (four
Enterococcus faecalis
, five
Enterococcus faecium
, and one
Enterococcus gallinarum
) as well as a vancomycin-susceptible control (ATCC 29212) strain of
E. faecalis
. The enterococci were exposed to doubling dilutions of linezolid for 12 passes. After the final passage, the linezolid plate growing VRE contained a higher drug concentration with
E. faecalis
than with
E. faecium
. DNA sequencing of the 23S rRNA genes revealed that linezolid resistance in three
E. faecalis
isolates was associated with a guanine to uracil transversion at bp 2576, while the one
E. faecium
isolate for which the MIC was 16 μg/ml contained a guanine to adenine transition at bp 2505.