bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent progress on magnetic sensors with nanostructures and applications
Authors: Sugiyama Yoshinobu
Published: July 2002

Hall devices and magnetoresistors totaling a billion per year made of semiconductors are used for displacement sensors of brushless motors in a videotape recorder and disk driver, contactless switches, and bill detectors of vending machine. Conventional magnetic sensors typically have a 100-μm active region and 1 μm thickness. Two kinds of new magnetic sensors with high sensitivity and high resolution are presented. A semiconductor Hall device made of pseudomorphic InAlAs/InGaAs heterostructures with a high electron mobility of 16 000 and 160 000 cm2/V s, respectively, at 300 and 10 K can be operated in a wide temperature range. A 200-μm-square Hall device with a low impedance of 310 Ω and a very thin active layer of 10 nm has a large product sensitivity of 320 V/A T and a maximum magnetic sensitivity of 15 V/T at room temperature. The magnetic sensitivity for current drive increases with decreasing temperature but is constant below liquid-nitrogen temperature. It is expected that the quantum-well Hall device with low dimensional heterostructure has a nanoscale resolution with a high signal-to-noise ratio. Second, a vacuum magnetic sensor with a comb-shaped field emitter, gate, and a pair of splitted collectors is presented. The principle of operation is based on the galvanomagnetic effect in vacuum. The device has a higher magnetic sensitivity of 1000%/T compared with semiconductor sensors.
Aluminum chemical vapor deposition with new gas phase pretreatment using tetrakisdimethylamino-titanium for ultralarge-scale integrated-circuit metallization
Authors: Sugai K. , Okabayashi H. , Shinzawa T. , Kishida S. , Kobayashi A. , Yako T. , Kadokura H.
Published: July 2002

A new gas phase pretreatment method was developed for blanket Al chemical vapor deposition (CVD) used in ultralarge-scale integration metallization. This method uses a halogen-free Ti compound. The pretreatment process involves exposing substrates to a tetrakisdimethylamino-titanium atmosphere before the Al CVD. This significantly lowers the deposition temperature of CVD using dimethylaluminum-hydride, and thus Al films can be deposited on SiO2 even at 160 °C, where deposition would otherwise not occur. The deposited Al films have superior surface morphology due to higher Al island density in the early growth stage. Using this technique, V-shaped trenches with an opening width of 0.4 μm and a depth of 1.2 μm are successfully filled with Al.
Electron beam lithography digital pattern generator and electronics for generalized curvilinear structures
Authors: Anderson Erik H. , Boegli Volker , Muray Lawrence P.
Published: July 2002

A vector scan pattern generator, optimized for smooth curvilinear as well as rectilinear primitive shapes, has been designed and constructed. The pattern generator uses high-speed hardware to implement a set of second-order, quadratic equations to drive digital to analog converters and high-speed array processors to calculate the coefficients for these equations. The digital pattern generator package contains the high-speed digital, analog, and high-resolution analog electronics. The initial lithography results confirm the operation of the system and stepping rates of 40 MHz have been achieved.
Treatment of InP surfaces in radio frequency H2 and H2/CH4/Ar plasmas: In situ compositional analysis, etch rates, and surface roughness
Authors: Parmeter J. E. , Shul R. J. , Howard A. J. , Miller P. A.
Published: July 2002

The surface composition, etch rates, and surface roughness of indium phosphide (InP) surfaces treated in radio frequency (rf) hydrogen and hydrogen/argon/methane plasmas have been investigated using in situ Auger spectroscopy and ex situ scanning electron microscopy and atomic force microscopy. In agreement with most previous studies, hydrogen plasmas are found to completely remove surface carbon and oxygen impurities, but at the expense of some degree of surface phosphorus depletion. This depletion can be minimized by utilizing brief plasma exposure times and low rf power settings. Oxygen removal is found to be rate limiting in the production of a clean surface. InP etching in hydrogen/argon/methane can be performed either in a low density, capacitively coupled plasma mode, or in a high density, inductively coupled plasma mode. For operation in the low density regime, the etched surfaces have a constant and nearly stoichiometric composition, independent of plasma parameters. Etch rates vary from ∼20–400 Å/min, while the root mean square (rms) surface roughness varies from ∼20 to >400 Å. Both of these quantities show definite trends with changing plasma parameters, and, in particular, high etch rates and low surface roughness are both favored by increasing total plasma pressure and methane flow rate. Within the ranges studied, the etch rate is most strongly affected by the amount of hydrocarbon species reaching the surface, which can remove indium in the form of indium alkyl products. However, sputtering effects are also shown to be significant. Etching InP in the high density plasma mode gives an etch rate of ∼700 Å/min, but only at the expense of severe surface phosphorus depletion and rms surface roughness of ∼2000 Å. The breakdown of methane within the plasma under these conditions may serve to inhibit indium alkyl formation, and hence lead to the observed phosphorus depletion.
Effect of rapid thermal annealing on radio-frequency magnetron-sputtered GaN thin films and Au/GaN Schottky diodes
Authors: Wang Ching-Wu , Liao Jin-Yuan , Chen Chih-Liang , Lin Wen-Kuan , Su Yan-Kuin , Yokoyama Meiso
Published: July 2002

The structural and optical properties of rf magnetron-sputtered GaN thin films on p+-Si substrates have been accessed as a function of rapid thermal annealing (RTA) temperatures from 800 to 1000 °C. The evidence has revealed that higher RTA temperatures not only assist the GaN films in recrystallizing into stable hexagonal form but also enhance the near-band-edge emission of GaN films in the photoluminescence spectrum. Moreover, a deep electron trap (Et) with activation energy Ec−Et≅0.39 eV detected at the surface of higher-RTA-temperature-treated GaN films was asserted to be a nitrogen-vacancy-related defect that takes a defect-assisted-tunneling role in the forward conduction process of Au/GaN Schottky diode. The greater reverse leakage current and lower breakdown voltage are suggested to be due to the effects of a lower barrier height and higher ideality factor that occurred in the higher-RTA-temperature-treated samples.
Specular electron scattering in metallic thin films
Authors: Egelhoff W. F. , Chen P. J. , Powell C. J. , Parks D. , Serpa G. , McMichael R. D. , Martien D. , Berkowitz A. E.
Published: July 2002

Specular electron scattering at the surface of metallic thin films is an important phenomenon for a class of magnetic multilayers known as giant magnetoresistance (GMR) spin valves. In the very best GMR spin valves, a significant part of the GMR effect is attributable to specular electron scattering. We have investigated the importance of specular electron scattering by developing surface-modification techniques that produce diffuse electron scattering. We have used these techniques to investigate specular electron scattering in GMR spin valves and in pure metals. Some of the largest effects are found in Au films. It is noted that specular electron scattering will be a highly desirable property in future generations of microelectronic interconnects as the feature size approaches the mean free path of the conduction electrons. In order to meet the Semiconductor Industry Association Roadmap requirements for interconnect resistivity, interconnects with highly specular surfaces must be developed.
Combinatorial approach for the synthesis of terpolymers and their novel application as very-high-contrast resists for x-ray nanolithography
Authors: Gonsalves Kenneth E. , Wang Jianzhao , Wu Hengpeng
Published: July 2002

Novel resist systems for x-ray lithography, specifically optimized in terms of contrast enhancement are described. Based on terpolymers of methyl methacrylate (MMA)-tert-butylacrylate-polyhedral oligosilsesquioxanes (POSS) synthesized by solution polymerization, these systems were optimized by a combinatorial approach. It is shown that the mass ratio of MMA/POSS=85.7/14.3 leads to maximum contrast (23.5) without sacrificing the sensitivity (1350 mJ/cm2) which remains comparable to that of standard PMMA. Such major contrast enhancement shows that the above organic/inorganic nanocomposites are promising candidates for sub-100 nm lithography.
CF3(CF2)7(CH2)2SH Self-Assembled on Au and Subsequent Degradation Under the Influence of Ionizing Radiation as Measured by XPS
Authors: Wagner Anthony J. , Vecitis Chad D. , Fairbrother D. Howard
Published: July 2002

X-ray photoelectron spectra are shown for a semifluorinated self-assembled monolayer basd on 1H,1H,2H,2H-perfluorodecanethiol [CF3(CF2)7(CH2)2SH] absorbed on a polycrystalline gold substrate. The effect of x-ray irradiation on the defluorination of the film, studied by following the time dependent variation in the C 1s spectral region, is also shown. This information has been used to elucidate the mechanism and kinetics of the elementary reaction steps that comprise defluorination.
Relapse to Cocaine-Seeking After Hippocampal Theta Burst Stimulation
Authors: Vorel Stanislav R. , Liu Xinhe , Hayes Robert J. , Spector Jordan A. , Gardner Eliot L.
Published: July 2002

Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse).
Ubiquitination of a New Form of α-Synuclein by Parkin from Human Brain: Implications for Parkinson's Disease
Authors: Shimura Hideki , Schlossmacher Michael G. , Hattori Nobutaka , Frosch Matthew P. , Trockenbacher Alexander , Schneider Rainer , Mizuno Yoshikuni , Kosik Kenneth S. , Selkoe Dennis J.
Published: July 2002

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive accumulation in selected neurons of protein inclusions containing α-synuclein and ubiquitin. Rare inherited forms of PD are caused by autosomal dominant mutations in α-synuclein or by autosomal recessive mutations in parkin, an E3 ubiquitin ligase. We hypothesized that these two gene products interact functionally, namely, that parkin ubiquitinates α-synuclein normally and that this process is altered in autosomal recessive PD. We have now identified a protein complex in normal human brain that includes parkin as the E3 ubiquitin ligase, UbcH7 as its associated E2 ubiquitin conjugating enzyme, and a new 22-kilodalton glycosylated form of α-synuclein (αSp22) as its substrate. In contrast to normal parkin, mutant parkin associated with autosomal recessive PD failed to bind αSp22. In an in vitro ubiquitination assay, αSp22 was modified by normal but not mutant parkin into polyubiquitinated, high molecular weight species. Accordingly, αSp22 accumulated in a non-ubiquitinated form in parkin-deficient PD brains. We conclude that αSp22 is a substrate for parkin's ubiquitin ligase activity in normal human brain and that loss of parkin function causes pathological αSp22 accumulation. These findings demonstrate a critical biochemical reaction between the two PD-linked gene products and suggest that this reaction underlies the accumulation of ubiquitinated α-synuclein in conventional PD.
Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses
Authors: Hatta Masato , Gao Peng , Halfmann Peter , Kawaoka Yoshihiro
Published: July 2002

In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.
Centennial-Scale Holocene Climate Variability Revealed by a High-Resolution Speleothem δ
18
O Record from SW Ireland
Authors: McDermott Frank , Mattey David P. , Hawkesworth Chris
Published: July 2002

Evaluating the significance of Holocene submillennial δ
18
O variability in the Greenland ice cores is crucial for understanding how natural climate oscillations may modulate future anthropogenic warming. A high-resolution oxygen isotope record from a speleothem in southwestern Ireland provides evidence for centennial-scale δ
18
O variations that correlate with subtle δ
18
O changes in the Greenland ice cores, indicating regionally coherent variability in the early Holocene. Evidence for previously undetected early Holocene cooling events is presented, but mid- to late-Holocene ice rafting in the North Atlantic appears to have had little impact on δ
18
O at this ocean margin site.
The Role of DNA Methylation in Mammalian Epigenetics
Authors: Jones Peter A. , Takai Daiya
Published: July 2002

Genes constitute only a small proportion of the total mammalian genome, and the precise control of their expression in the presence of an overwhelming background of noncoding DNA presents a substantial problem for their regulation. Noncoding DNA, containing introns, repetitive elements, and potentially active transposable elements, requires effective mechanisms for its long-term silencing. Mammals appear to have taken advantage of the possibilities afforded by cytosine methylation to provide a heritable mechanism for altering DNA-protein interactions to assist in such silencing. Genes can be transcribed from methylation-free promoters even though adjacent transcribed and nontranscribed regions are extensively methylated. Gene promoters can be used and regulated while keeping noncoding DNA, including transposable elements, suppressed. Methylation is also used for long-term epigenetic silencing of X-linked and imprinted genes and can either increase or decrease the level of transcription, depending on whether the methylation inactivates a positive or negative regulatory element.
The Spin Temperature of NH
3
in Comet C/1999S4 (LINEAR)
Authors: Kawakita Hideyo , Watanabe Jun-ichi , Ando Hiroyasu , Aoki Wako , Fuse Tetsuharu , Honda Satoshi , Izumiura Hideyuki , Kajino Toshitaka , Kambe Eiji , Kawanomoto Satoshi , Noguchi Kunio , Okita Kiichi , Sadakane Kozo , Sato Bun'ei , Takada-Hidai Masahide , Takeda Yoichi , Usuda Tomonori , Watanabe Etsuji , Yoshida Michitoshi
Published: July 2002

A high-dispersion spectrum of Comet C/1999S4 (LINEAR) was obtained in the optical region with the high-dispersion spectrograph on the Subaru telescope when the comet was 0.863 astronomical units from the Sun before its disintegration. We obtained high signal-to-noise ratio emission lines of the cometary NH
2
bands from which an ortho-to-para ratio (OPR) of 3.33 ± 0.07 was derived on the basis of a fluorescence excitation model. Assuming that cometary NH
2
mainly originates from ammonia through photodissociation, the derived OPR of NH
2
molecules should reflect that of ammonia, which provides information on the environment of molecular formation or condensation and of the thermal history of cometary ices. Assuming that the OPR of ammonia in comets was unchanged in the nucleus, the derived spin temperature of ammonia (28 ± 2 kelvin) suggests that a formation region of the cometary ammonia ice was between the orbit of Saturn and that of Uranus in the solar nebula.
Discoidal Impressions and Trace-Like Fossils More Than 1200 Million Years Old
Authors: Rasmussen Birger , Bengtson Stefan , Fletcher Ian R. , McNaughton Neal J.
Published: July 2002

The Stirling Range Formation of southwestern Australia contains discoidal impressions and trace-like fossils in tidal sandstones. The various disks have previously been linked to the Ediacaran biota, younger than 600 million years old. From this unit, we report U-Th-Pb geochronology of detrital zircon and monazite, as well as low-grade metamorphic monazite, constraining the depositional age to between 2016 ± 6 and 1215 ± 20 million years old. Although nonbiological origins for the discoidal impressions cannot be completely discounted, the structures resembling trace fossils clearly have a biological origin and suggest the presence of vermiform, mucus-producing, motile organisms.
Glacial to Interglacial Fluctuations in Productivity in the Equatorial Pacific as Indicated by Marine Barite
Authors: Paytan A. , Kastner M. , Chavez F. P.
Published: July 2002

An empirical correlation between marine barite (BaSO
4
) accumulation rate in core-top sediment samples from two equatorial Pacific transects (at 140°W and 110°W) and the estimated primary productivity of the overlying water column were used to evaluate glacial to interglacial changes in productivity. Fluctuations in barite accumulation rates down-core indicate that during glacial periods of the past 450,000 years, the productivity in the central and eastern equatorial Pacific was about two times that during intervening interglacial periods. This result is consistent with other evidence that productivity was high in the eastern and central equatorial Pacific during the last glacial.
Structure of DNA-Cationic Liposome Complexes: DNA Intercalation in Multilamellar Membranes in Distinct Interhelical Packing Regimes
Authors: Rädler Joachim O. , Koltover Ilya , Salditt Tim , Safinya Cyrus R.
Published: July 2002

Cationic liposomes complexed with DNA (CL-DNA) are promising synthetically based nonviral carriers of DNA vectors for gene therapy. The solution structure of CL-DNA complexes was probed on length scales from subnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addition of either linear λ-phage or plasmid DNA to CLs resulted in an unexpected topological transition from liposomes to optically birefringent liquid-crystalline condensed globules. X-ray diffraction of the globules revealed a novel multilamellar structure with alternating lipid bilayer and DNA monolayers. The λ-DNA chains form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the λ-DNA interaxial spacing expands between 24.5 and 57.1 angstroms upon lipid dilution and is indicative of a long-range electrostatic-induced repulsion that is possibly enhanced by chain undulations.
Direct Measurement of a Tethered Ligand-Receptor Interaction Potential
Authors: Wong Joyce Y. , Kuhl Tonya L. , Israelachvili Jacob N. , Mullah Nasreen , Zalipsky Samuel
Published: July 2002

Many biological recognition interactions involve ligands and receptors that are tethered rather than rigidly bound on a cell surface. A surface forces apparatus was used to directly measure the force-distance interaction between a polymer-tethered ligand and its receptor. At separations near the fully extended tether length, the ligands rapidly lock onto their binding sites, pulling the ligand and receptor together. The measured interaction potential and its dynamics can be modeled with standard theories of polymer and colloidal interactions.
Low-Temperature Nonoxidative Activation of Methane over
H
-Galloaluminosilicate (MFI) Zeolite
Authors: Choudhary Vasant R. , Kinage Anil K. , Choudhary Tushar V.
Published: July 2002

Conversion of methane to higher hydrocarbons by its low-temperature activation without forming undesirable carbon oxides is of great scientific and practical importance. Methane can be highly activated, yielding high rates of conversion to higher hydrocarbons and aromatics (10 to 45 percent) at low temperatures (400° to 600°C), by its reaction over
H
-galloaluminosilicate ZSM-5 type (MFI) zeolite in the presence of alkenes or higher alkanes. The methane activation results from its hydrogen-transfer reaction with alkenes.
A Cyanobacterial Phytochrome Two-Component Light Sensory System
Authors: Yeh Kuo-Chen , Wu Shu-Hsing , Murphy John T. , Lagarias J. Clark
Published: July 2002

The biliprotein phytochrome regulates plant growth and developmental responses to the ambient light environment through an unknown mechanism. Biochemical analyses demonstrate that phytochrome is an ancient molecule that evolved from a more compact light sensor in cyanobacteria. The cyanobacterial phytochrome Cph1 is a light-regulated histidine kinase that mediates red, far-red reversible phosphorylation of a small response regulator, Rcp1 (response regulator for cyanobacterial phytochrome), encoded by the adjacent gene, thus implicating protein phosphorylation-dephosphorylation in the initial step of light signal transduction by phytochrome.
Role of Dynamin in the Formation of Transport Vesicles from the Trans-Golgi Network
Authors: Jones Steven M. , Howell Kathryn E. , Henley John R. , Cao Hong , McNiven Mark A.
Published: July 2002

Dynamin guanosine triphosphatases support the scission of clathrin-coated vesicles from the plasmalemma during endocytosis. By fluorescence microscopy of cultured rat hepatocytes, a green fluorescent protein–dynamin II fusion protein localized with clathrin-coated vesicles at the Golgi complex. A cell-free assay was utilized to demonstrate the role of dynamin in vesicle formation at the trans-Golgi. Addition of peptide-specific anti-dynamin antibodies to the assay mixture inhibited both constitutive exocytic and clathrin-coated vesicle formation. Immunodepletion of dynamin proteins also inhibited vesicle formation, and budding efficiency was restored upon readdition of purified dynamin. These data suggest that dynamin participates in the formation of distinct transport vesicles from the trans-Golgi network.
Thymocyte Development in the Absence of Pre-T Cell Receptor Extracellular Immunoglobulin Domains
Authors: Irving Bryan A. , Alt Frederick W. , Killeen Nigel
Published: July 2002

Immature thymocytes express a pre–T cell receptor (pre-TCR) composed of the TCRβ chain paired with pre-Tα. Signals from this receptor are essential for passage of thymocytes through a key developmental checkpoint in the thymus. These signals were efficiently delivered in vivo by a truncated form of the murine pre-TCR that lacked all of its extracellular immunoglobulin domains. De novo expression of the truncated pre-TCR or an intact αβTCR was sufficient to activate characteristic TCR signaling pathways in a T cell line. These findings support the view that recognition of an extracellular ligand is not required for pre-TCR function.
Drosophila
Synapse Formation: Regulation by Transmembrane Protein with Leu-Rich Repeats, CAPRICIOUS
Authors: Shishido Emiko , Takeichi Masatoshi , Nose Akinao
Published: July 2002

Upon reaching the target region, neuronal growth cones transiently search through potential targets and form synaptic connections with only a subset of these. The
capricious
(
caps
) gene may regulate these processes in
Drosophila. caps
encodes a transmembrane protein with leucine-rich repeats (LRRs). During the formation of neuromuscular synapses,
caps
is expressed in a small number of synaptic partners, including muscle 12 and the motorneurons that innervate it. Loss-of-function and ectopic expression of
caps
alter the target specificity of muscle 12 motorneurons, indicating a role for
caps
in selective synapse formation.
Genetic Dissection of a Mammalian Replicator in the Human β-Globin Locus
Authors: Aladjem Mirit I. , Rodewald Luo Wei , Kolman John L. , Wahl Geoffrey M.
Published: July 2002

The timing and localization of DNA replication initiation in mammalian cells are heritable traits, but it is not known whether initiation requires specific DNA sequences. A site-specific recombination strategy was used to show that DNA sequences previously identified as replication initiation sites could initiate replication when transferred to new chromosomal locations. An 8-kilobase DNA sequence encompassing the origin of DNA replication in the human β-globin locus initiated replication in the simian genome. Specific deletions within the globin origin did not initiate replication in these chromosomal sites. These data suggest that initiation of DNA replication in mammalian cells requires specific sequence information and extend the replicon hypothesis to higher eukaryotes.
Independent and Epigenetic Regulation of the Interleukin-4 Alleles in CD4
+
T Cells
Authors: Bix Mark , Locksley Richard M.
Published: July 2002

How an individual effector T cell acquires a particular cytokine expression pattern from many possible patterns remains unclear. CD4
+
T cells from F
1
mice, which allowed assignment of the parental origin of interleukin-4 (IL-4) transcripts, were divided into clones that expressed IL-4 biallelically or monoallelically from either allele. The allelic pattern was transmitted as a stable epigenetic trait. Regulation of cytokine expression by a mechanism that treats each allele independently suggests a probabilistic process by which a diverse repertoire of combinatorially assorted cytokine gene expression patterns could be generated among the clonally related daughters of a single precursor cell.
Implications of Mars Pathfinder Data for the Accretion History of the Terrestrial Planets
Authors: Bertka Constance M. , Fei Yingwei
Published: July 2002

Accretion models of the terrestrial planets often assume planetary bulk compositions with nonvolatile element abundance ratios equivalent to those of C1 carbonaceous chondrites. The moment of inertia factor of Mars reported by the Pathfinder team is inconsistent with a bulk planet C1 Fe/Si ratio or Fe content, which suggests that C1 chondrite accretion models are insufficient to explain the formation of Mars and the other terrestrial planets. Future planetary accretion models will have to account for variations in bulk Fe/Si ratios among the terrestrial planets.
Rule Learning by Seven-Month-Old Infants
Authors: Marcus G. F. , Vijayan S. , Bandi Rao S. , Vishton P. M.
Published: July 2002

A fundamental task of language acquisition is to extract abstract algebraic rules. Three experiments show that 7-month-old infants attend longer to sentences with unfamiliar structures than to sentences with familiar structures. The design of the artificial language task used in these experiments ensured that this discrimination could not be performed by counting, by a system that is sensitive only to transitional probabilities, or by a popular class of simple neural network models. Instead, these results suggest that infants can represent, extract, and generalize abstract algebraic rules.
Negative Regulation of Wingless Signaling by D-Axin, a
Drosophila
Homolog of Axin
Authors: Hamada Fumihiko , Tomoyasu Yoshinori , Takatsu Yoshihiro , Nakamura Makoto , Nagai Shin-ichi , Suzuki Akiko , Fujita Fumitaka , Shibuya Hiroshi , Toyoshima Kumao , Ueno Naoto , Akiyama Tetsu
Published: July 2002

Wnt/Wingless directs many cell fates during development. Wnt/Wingless signaling increases the amount of β-catenin/Armadillo, which in turn activates gene transcription. Here the
Drosophila
protein D-Axin was shown to interact with Armadillo and D-APC. Mutation of
d-axin
resulted in the accumulation of cytoplasmic Armadillo and one of the Wingless target gene products, Distal-less. Ectopic expression of
d-axin
inhibited Wingless signaling. Hence, D-Axin negatively regulates Wingless signaling by down-regulating the level of Armadillo. These results establish the importance of the Axin family of proteins in Wnt/Wingless signaling in
Drosophila
.
Epitaxial Cubic Gadolinium Oxide as a Dielectric for Gallium Arsenide Passivation
Authors: Hong M. , Kwo J. , Kortan A. R. , Mannaerts J. P. , Sergent A. M.
Published: July 2002

Epitaxial growth of single-crystal gadolinium oxide dielectric thin films on gallium arsenide is reported. The gadolinium oxide film has a cubic structure isomorphic to manganese oxide and is (110)-oriented in single domain on the (100) gallium arsenide surface. The gadolinium oxide film has a dielectric constant of approximately 10, with low leakage current densities of about 10
–9
to 10
–10
amperes per square centimeter at zero bias. Typical breakdown field is 4 megavolts per centimeter for an oxide film 185 angstroms thick and 10 megavolts per centimeter for an oxide 45 angstroms thick. Both accumulation and inversion layers were observed in the gadolinium oxide–gallium arsenide metal oxide semiconductor diodes, using capacitance-voltage measurements. The ability to grow thin single-crystal oxide films on gallium arsenide with a low interfacial density of states has great potential impact on the electronic industry of compound semiconductors.
Ca
2+
-Induced Apoptosis Through Calcineurin Dephosphorylation of BAD
Authors: Wang Hong-Gang , Pathan Nuzhat , Ethell Iryna M. , Krajewski Stanislaw , Yamaguchi Yu , Shibasaki Futoshi , McKeon Frank , Bobo Tanya , Franke Thomas F. , Reed John C.
Published: July 2002

The Ca
2+
-activated protein phosphatase calcineurin induces apoptosis, but the mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-x
L
and promoting apoptosis. The Ca
2+
-induced dephosphorylation of BAD correlated with its dissociation from 14-3-3 in the cytosol and translocation to mitochondria where Bcl-x
L
resides. In hippocampal neurons,
l
-glutamate, an inducer of Ca
2+
influx and calcineurin activation, triggered mitochondrial targeting of BAD and apoptosis, which were both suppressible by coexpression of a dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this phosphatase. Thus, a Ca
2+
-inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells.
Sources of Mathematical Thinking: Behavioral and Brain-Imaging Evidence
Authors: Dehaene S. , Spelke E. , Pinel P. , Stanescu R. , Tsivkin S.
Published: July 2002

Does the human capacity for mathematical intuition depend on linguistic competence or on visuo-spatial representations? A series of behavioral and brain-imaging experiments provides evidence for both sources. Exact arithmetic is acquired in a language-specific format, transfers poorly to a different language or to novel facts, and recruits networks involved in word-association processes. In contrast, approximate arithmetic shows language independence, relies on a sense of numerical magnitudes, and recruits bilateral areas of the parietal lobes involved in visuo-spatial processing. Mathematical intuition may emerge from the interplay of these brain systems.
Experimental Evidence for the Source of Excess Sulfur in Explosive Volcanic Eruptions
Authors: Keppler Hans
Published: July 2002

The amounts of sulfur released in explosive volcanic eruptions are often orders of magnitude larger than those expected to result from the degassing of the erupted SiO
2
-rich magma. Experimentally measured fluid/melt partition coefficients of sulfur ranged from 47 under oxidizing conditions (where SO
2
is the dominant sulfur species in the fluid) to 468 under reducing conditions (where H
2
S dominates). Therefore, a few weight percent of hydrous fluid accumulated in the top of a magma chamber may extract most of the sulfur out of the entire magma reservoir and generate sulfur excesses upon eruption.
Regular and Irregular Patterns in Semiarid Vegetation
Authors: Klausmeier Christopher A.
Published: July 2002

Vegetation in many semiarid regions is strikingly patterned, forming regular stripes on hillsides and irregular mosaics on flat ground. A simple model of plant and water dynamics based on ecologically realistic assumptions and with reasonable parameter values captures both of these types of patterns. The regular patterns result from a Turing-like instability; the irregular patterns arise when the ecological dynamics amplify slight small-scale topographic variability. Because of the close agreement between observations and these theoretical results, this system provides a clear example of how nonlinear mechanisms can be important in determining the spatial structure of plant communities.
Long-Term Depression in Hippocampal Interneurons: Joint Requirement for Pre- and Postsynaptic Events
Authors: Laezza Fernanda , Doherty James J. , Dingledine Raymond
Published: July 2002

Long-term depression (LTD) is a well-known form of synaptic plasticity of principal neurons in the mammalian brain. Whether such changes occur in interneurons is still controversial. CA3 hippocampal interneurons expressing Ca
2+
-permeable AMPA receptors exhibited LTD after tetanic stimulation of CA3 excitatory inputs. LTD was independent of NMDA receptors and required both Ca
2+
influx through postsynaptic AMPA receptors and activation of presynaptic mGluR7-like receptors. These results point to the capability of interneurons to undergo plastic changes of synaptic strength through joint activation of pre- and postsynaptic glutamate receptors.
Biosequence Exegesis
Authors: Boguski Mark S.
Published: July 2002

Annotation of large-scale gene sequence data will benefit from comprehensive and consistent application of well-documented, standard analysis methods and from progressive and vigilant efforts to ensure quality and utility and to keep the annotation up to date. However, it is imperative to learn how to apply information derived from functional genomics and proteomics technologies to conceptualize and explain the behaviors of biological systems. Quantitative and dynamical models of systems behaviors will supersede the limited and static forms of single-gene annotation that are now the norm. Molecular biological epistemology will increasingly encompass both teleological and causal explanations.
A Global View of Martian Surface Compositions from MGS-TES
Authors: Bandfield Joshua L. , Hamilton Victoria E. , Christensen Philip R.
Published: July 2002

Thermal Emission Spectrometer (TES) data from the Mars Global Surveyor (MGS) are used to determine compositions and distributions of martian low-albedo regions. Two surface spectral signatures are identified from low-albedo regions. Comparisons with spectra of terrestrial rock samples and deconvolution results indicate that the two compositions are a basaltic composition dominated by plagioclase feldspar and clinopyroxene and an andesitic composition dominated by plagioclase feldspar and volcanic glass. The distribution of the two compositions is split roughly along the planetary dichotomy. The basaltic composition is confined to older surfaces, and the more silicic composition is concentrated in the younger northern plains.
Positioning of the Mitotic Spindle by a Cortical-Microtubule Capture Mechanism
Authors: Lee Laifong , Tirnauer Jennifer S. , Li Junjun , Schuyler Scott C. , Liu Jenny Y. , Pellman David
Published: July 2002

Correct positioning of the mitotic spindle is critical for cell division and development. Spindle positioning involves a search-and-capture mechanism whereby dynamic microtubules find and then interact with specific sites on the submembrane cortex. Genetic, biochemical, and imaging experiments suggest a mechanism for cortical-microtubule capture. Bim1p, located at microtubule distal ends, bound Kar9p, a protein associated with the daughter cell cortex. Bim1p is the yeast ortholog of human EB1, a binding partner for the adenomatous polyposis coli tumor suppressor. EB1 family proteins may have a general role in linking the microtubule cytoskeleton to cortical polarity determinants.
Galileo at Io: Results from High-Resolution Imaging
Authors: McEwen A. S. , Belton M. J. S. , Breneman H. H. , Fagents S. A. , Geissler P. , Greeley R. , Head J. W. , Hoppa G. , Jaeger W. L. , Johnson T. V. , Keszthelyi L. , Klaasen K. P. , Lopes-Gautier R. , Magee K. P. , Milazzo M. P. , Moore J. M. , Pappalardo R. T. , Phillips C. B. , Radebaugh J. , Schubert G. , Schuster P. , Simonelli D. P. , Sullivan R. , Thomas P. C. , Turtle E. P. , Williams D. A.
Published: July 2002

During late 1999/early 2000, the solid state imaging experiment on the Galileo spacecraft returned more than 100 high-resolution (5 to 500 meters per pixel) images of volcanically active Io. We observed an active lava lake, an active curtain of lava, active lava flows, calderas, mountains, plateaus, and plains. Several of the sulfur dioxide–rich plumes are erupting from distal flows, rather than from the source of silicate lava (caldera or fissure, often with red pyroclastic deposits). Most of the active flows in equatorial regions are being emplaced slowly beneath insulated crust, but rapidly emplaced channelized flows are also found at all latitudes. There is no evidence for high-viscosity lava, but some bright flows may consist of sulfur rather than mafic silicates. The mountains, plateaus, and calderas are strongly influenced by tectonics and gravitational collapse. Sapping channels and scarps suggest that many portions of the upper ∼1 kilometer are rich in volatiles.
Perception of Environmental Signals by a Marine Diatom
Authors: Falciatore Angela , d'Alcalà Maurizio Ribera , Croot Peter , Bowler Chris
Published: July 2002

Diatoms are a key component of marine ecosystems and are extremely important for the biogeochemical cycling of silica and as contributors to global fixed carbon. However, the answers to fundamental questions such as what diatoms can sense in their environment, how they respond to external signals, and what factors control their life strategies are largely unknown. We generated transgenic diatom cells containing the calcium-sensitive photoprotein aequorin to determine whether changes in calcium homeostasis are used to respond to relevant environmental stimuli. Our results reveal sensing systems for detecting and responding to fluid motion (shear stress), osmotic stress, and iron, a key nutrient that controls diatom abundance in the ocean.
Dysfunction in the Neural Circuitry of Emotion Regulation--A Possible Prelude to Violence
Authors: Davidson Richard J. , Putnam Katherine M. , Larson Christine L.
Published: July 2002

Emotion is normally regulated in the human brain by a complex circuit consisting of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several other interconnected regions. There are both genetic and environmental contributions to the structure and function of this circuitry. We posit that impulsive aggression and violence arise as a consequence of faulty emotion regulation. Indeed, the prefrontal cortex receives a major serotonergic projection, which is dysfunctional in individuals who show impulsive violence. Individuals vulnerable to faulty regulation of negative emotion are at risk for violence and aggression. Research on the neural circuitry of emotion regulation suggests new avenues of intervention for such at-risk populations.
Protein Dynamics: Implications for Nuclear Architecture and Gene Expression
Authors: Misteli Tom
Published: July 2002

Studies of nuclear architecture reveal that the dynamic properties of proteins in the nucleus are critical for their function. The high mobility of proteins ensures their availability throughout the nucleus; their dynamic interplay generates an ever-changing, but overall stable, architectural framework, within which nuclear processes take place. As a consequence, overall nuclear morphology is determined by the functional interactions of nuclear components. The observed dynamic properties of nuclear proteins are consistent with a central role for stochastic mechanisms in gene expression and nuclear architecture.
Evaluation of Rifalazil in a Combination Treatment Regimen as an Alternative to Isoniazid-Rifampin Therapy in a Mouse Tuberculosis Model
Authors: Lenaerts Anne M. , Chase Sharon E. , Cynamon Michael H.
Published: July 2002

The newer rifamycin, rifalazil (RLZ) (previously known as KRM-1648), has been shown in prior experiments to be a highly potent drug against
Mycobacterium tuberculosis
. In this report, we studied the efficacy of RLZ in combination with pyrazinamide (PZA) and ethambutol (EMB) in a long-term in vivo experiment and compared their activity with the isoniazid (INH)-rifampin (RIF) combination which is presently used in the clinic. Combinations of RLZ with PZA alone or with both PZA and EMB were both found to have sterilizing activities comparable to that of the INH-RIF combination but significantly better activity with respect to relapse of infection. These results suggest that RLZ, or other agents with similar activity, could be combined with available agents to act as a potential alternative drug regimen to the currently used INH-RIF combination.
Identification of a Cyclase Gene Dictating the C-9 Stereochemistry of Anthracyclines from
Streptomyces nogalater
Authors: Torkkell Sirke , Kunnari Tero , Palmu Kaisa , Hakala Juha , Mäntsälä Pekka , Ylihonko Kristiina
Published: July 2002

Nogalamycin is an anthracycline antibiotic produced by
Streptomyces nogalater
. Its aglycone has a unique stereochemistry (7S, 9S, 10R) compared to that of most other anthracyclines (7S, 9R, 10R). The gene
sno
aL, encoding a nogalonic acid methyl ester cyclase for nogalamycin, was used to generate nogalamycinone, demonstrating that the single cyclase dictates the C-9 stereochemistry of anthracyclines.
Biochemical Sequence Analyses of GES-1, a Novel Class A Extended-Spectrum β-Lactamase, and the Class 1 Integron In52 from
Klebsiella pneumoniae
Authors: Poirel Laurent , Le Thomas Isabelle , Naas Thierry , Karim Amal , Nordmann Patrice
Published: July 2002

Klebsiella pneumoniae
ORI-1 was isolated in 1998 in France from a rectal swab of a 1-month-old girl who was previously hospitalized in Cayenne Hospital, Cayenne, French Guiana. This strain harbored a ca. 140-kb nontransferable plasmid, pTK1, that conferred an extended-spectrum cephalosporin resistance profile antagonized by the addition of clavulanic acid, tazobactam, or imipenem. The gene for GES-1 (Guiana extended-spectrum β-lactamase) was cloned, and its protein was expressed in
Escherichia coli
DH10B, where this pI-5.8 β-lactamase of a ca. 31-kDa molecular mass conferred resistance to oxyimino cephalosporins (mostly to ceftazidime). GES-1 is weakly related to the other plasmid-located Ambler class A extended-spectrum β-lactamases (ESBLs). The highest percentage of amino acid identity was obtained with the carbenicillinase GN79 from
Proteus mirabilis
; with YENT, a chromosome-borne penicillinase from
Yersinia enterocolitica
; and with L-2, a chromosome-borne class A cephalosporinase from
Stenotrophomonas maltophilia
(36% amino acid identity each). However, a dendrogram analysis showed that GES-1 clustered within a class A ESBL subgroup together with ESBLs VEB-1 and PER-1. Sequencing of a 7,098-bp DNA fragment from plasmid pTK1 revealed that the GES-1 gene was located on a novel class 1 integron named In52 that was characterized by (i) a 5′ conserved segment containing an
intI1
gene possessing two putative promoters, P
1
and P
2
, for coordinated expression of the downstream antibiotic resistance genes and an
attI1
recombination site; (ii) five antibiotic gene cassettes,
bla
GES-1
,
aac(6′)Ib
′ (gentamicin resistance and amikacin susceptibility),
dfrXVb
(trimethoprim resistance), a novel chloramphenicol resistance gene (
cmlA4
), and
aadA2
(streptomycin-spectinomycin resistance); and (iii) a 3′ conserved segment consisting of
qacEΔ1
and
sulI
. The
bla
GES-1
and
aadA2
gene cassettes were peculiar, since they lacked a typical 59-base element. This work identified the second class A ESBL gene of a non-TEM, non-SHV series which was located in the plasmid and integron, thus providing it additional means for its spread and its expression.
Evaluation of Rifalazil in Long-Term Treatment Regimens for Tuberculosis in Mice
Authors: Shoen Carolyn M. , Chase Sharon E. , DeStefano Michelle S. , Harpster Tami S. , Chmielewski Alex J. , Cynamon Michael H.
Published: July 2002

Previous experiments with rifalazil (RLZ) (also known as KRM-1648) in combination with isoniazid (INH) demonstrated its potential for short-course treatment of
Mycobacterium tuberculosis
infection. In this study we investigated the minimum RLZ-INH treatment time required to eradicate
M. tuberculosis
in a murine model. RLZ-INH treatment for 6 weeks or longer led to a nonculturable state. Groups of mice treated in parallel were killed following an observation period to evaluate regrowth. RLZ-INH treatment for a minimum of 10 weeks was necessary to maintain a nonculturable state through the observation period. Pyrazinamide (PZA) was added to this regimen to determine whether the treatment duration could be further reduced. In this model, the addition of PZA did not shorten the duration of RLZ-INH treatment required to eradicate
M. tuberculosis
from mice. The addition of PZA reduced the number of mice in which regrowth occurred, although the reduction was not statistically significant.
Linezolid Therapy of Vancomycin-Resistant
Enterococcus faecium
Experimental Endocarditis
Authors: Patel Robin , Rouse Mark S. , Piper Kerryl E. , Steckelberg James M.
Published: July 2002

We compared the activities of linezolid (25 mg/kg of body weight, administered intraperitoneally every 8 h) and of vancomycin (25 mg/kg of body weight, administered intraperitoneally every 8 h) in a rat model of
vanA
vancomycin-resistant
Enterococcus faecium
experimental endocarditis. Results were expressed as median log
10
CFU per gram of vegetation after 3 days of treatment. The median log
10
CFU per gram of vegetation was 10.1 among 7 untreated control animals, 10.2 among 9 vancomycin-treated animals, and 7.9 among 10 linezolid-treated animals. Linezolid treatment was more active (
P
< 0.05) than vancomycin treatment or no treatment.
Pharmacokinetics of Clinafloxacin after Single and Multiple Doses
Authors: Randinitis Edward J. , Brodfuehrer Joanne I. , Eiseman Irene , Vassos Artemios B.
Published: July 2002

Clinafloxacin (CI-960) is a potent broad-spectrum, fluoroquinolone antibiotic that has been studied for parenteral and oral administration in patients with serious infections. The objectives of these studies were to examine the pharmacokinetics and safety of clinafloxacin following administration of single and twice-daily intravenous (i.v.) and oral doses to volunteers. Plasma and urine samples were assayed by validated liquid chromatographic methods, and pharmacokinetic parameter values were determined by noncompartmental methods. Safety was evaluated by clinical observation and laboratory tests. Absorption was rapid after oral administration, with maximum concentrations in plasma (Cmax) generally occurring within 2 h. Concentrations in plasma declined biexponentially, with an average terminal half-life of 4 to 6 h after single doses and 5 to 7 h after multiple doses. Increases inCmaxand area under the concentration-time curves (AUC) were generally proportional to the dose. The volume of distribution was much greater than total body water. Approximately 40 to 75% of the clinafloxacin doses were excreted unchanged into urine. Absolute bioavailability of orally administered clinafloxacin was approximately 90% and did not change with increasing dose. Therefore, switching patients from i.v. to oral dosing should achieve similar concentrations in plasma. The tolerability of clinafloxacin was acceptable. No serious adverse events occurred.Cmaxvalues and minimum plasma clinafloxacin concentrations during multiple dosing exceeded MICs for a wide range of organisms.