bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative study of ageing epiglottal taste buds in humans
Authors: Kano Mitsuhiro , Shimizu Yoshinaka , Okayama Keisuke , Kikuchi Masayoshi
Published: July 2007

Objectives:  This investigation aimed to demonstrate age‐related changes of taste buds on the human epiglottis using histomorphometrical analysis.

Methods:  Histological observation and measurement of taste bud density were performed on oral and laryngeal surfaces of 237 human epiglottises (138 male and 99 females). The cases were divided into two age groups: 67 cases in the younger group, for subjects aged 10–39 years and 170 cases in the older group, for those aged 70–98 years. Each epiglottis was investigated at the upper and middle height levels.

Results:  The mean density of taste buds significantly decreased on the laryngeal surfaces in the older group. Most taste buds were present in the upper height level on the laryngeal surfaces which were covered with thin and flat stratified squamous epithelium. The covering epithelium revealed developed epithelial ridges on the oral surfaces without taste buds. These results suggest a relationship between the existence of taste buds and the thickness of the covering epithelium.

Conclusions:  The presence of taste buds in the epiglottises of elderly people was demonstrated. In addition, the decrease of these taste buds with advancing age was clarified.
Molecular subtyping of feline immunodeficiency virus from domestic cats in Australia
Authors: KANN RKC , KYAW‐TANNER MT , SEDDON JM , LEHRBACH PR , ZWIJNENBERG RJG , MEERS J.
Published: July 2007

Objective To determine the prevalent subtypes of feline immunodeficiency virus (FIV) present in the domestic cat population of Australia.

Method Blood samples were collected from 41 FIV antibody positive cats from four cities across Australia. Following DNA extraction, polymerase chain reaction (PCR) was performed to amplify the variable V3‐V5 region of the envelope (env) gene. Genotypes were assessed by direct sequencing of PCR products and comparison with previously reported FIV sequences. Phylogenetic analysis allowed classification of the Australian sequences into the appropriate subtype.

Results Of the 41 FIV samples, 40 were found to cluster with previously reported subtype A isolates, whilst the remaining sample grouped within subtype B.

Conclusions Subtype A was found to be the predominant FIV subtype present in Australia, although subtype B was also found. These results broaden our knowledge of the genetic diversity of FIV and the associated implications for preventative, diagnostic and therapeutic approaches.
Pleuropneumonia as a sequela of myelography and general anaesthesia in a Thoroughbred colt
Authors: RAINGER JE , HUGHES KJ , KESSELL A. , DART CM
Published: July 2007

A 3‐year‐old Thoroughbred colt was presented to the University Veterinary Centre Camden for evaluation of ataxia. The horse was anaesthetised to facilitate cervical radiography and myelographic examination of the spinal cord. Recovery from anaesthesia was uneventful. Five days after general anaesthesia the horse re‐presented with pleuropneumonia. It was euthanased 24 hours after presentation on humane grounds. Necropsy revealed severe tracheal erosion over the middle third of the ventral surface of the trachea, pleuropneumonia and narrowing of the cervical cord between C4 and C6. It is postulated that extension and flexion of the neck during myelography resulted in movement of the endotracheal tube cuff, causing the tracheal lesion and predisposing the colt to pleuropneumonia. Severe tracheal lesions and pleuropneumonia have not been reported as sequela of equine myelography, and should be considered as possible complications following repeated cervical manipulation during myelography in the horse.
Preparation of transparent conducting B-doped ZnO films by vacuum arc plasma evaporation
Authors: Miyata Toshihiro , Honma Yasunori , Minami Tadatsugu
Published: July 2007

Highly transparent and conductive B-doped ZnO (BZO) thin films have been prepared by a newly developed vacuum arc plasma evaporation method that provided high-rate film depositions using sintered BZO pellets and fragments. The obtained electrical and optical properties of the deposited BZO thin films were considerably affected by the deposition conditions as well as the preparation method of the BZO pellets and fragments used. The lowest thin film resistivity was obtained with a B doping content [B∕(B+Zn) atomic ratio] of approximately 1at.%. A resistivity as low as 5×10−4Ωcm and an average transmittance above about 80% in the wavelength range of 400–1300nm were obtained in BZO films prepared with a thickness above approximately 400nm at a substrate temperature of 200°C. In addition, a low resistivity of 7.97×10−4Ωcm and average transmittances above about 80% in the visible wavelength range were obtained in a BZO film prepared at a substrate temperature of 100°C and an O2 gas flow rate of 10SCCM (SCCM denotes cubic centimeter per minute at STP). The deposition rate of BZO films was typically 170nm∕min with a cathode plasma power of 4.5kW.
Ordered Au(111) layers on Si(111)
Authors: Silva Ana , Pedersen Kjeld , Diekhöner Lars , Morgen Per , Li Zheshen
Published: July 2007

Ordered Au films are grown on top of a thin (seven-layer) Cu film acting as a buffer between Au and a Si(111) substrate and characterized with synchrotron radiation photoemission spectroscopy. A sharp Shockley surface state characteristic of Au(111) is seen in the valence band spectra together with structures in the sp part of the band that disperse toward the sp band edge for growing film thickness. These structures are ascribed to quantum well effects. The Au film shows sharp (111) low energy electron diffraction patterns for a film thickness above eight layers.
Synthesis and characterization of nanoscale Al–Si–O gradient membranes
Authors: Trouillet V. , Tröße H. , Bruns M. , Nold E. , White R. G.
Published: July 2007

Novel ultrathin gas-permeable Al–Si-oxide membranes have been developed by means of ion induced chemical vapor deposition in order to improve the gas analytical performance of an electronic nose. Dependent on the used precursor tailored Al∕Si concentration ratios and even concentration gradients are attainable. The diversity in chemical composition and thickness across the gas sensor microarray has been proven by the combination of ellipsometry for the freshly prepared membrane and line scans derived from Auger electron spectroscopy and angle resolved x-ray photoelectron spectroscopy, respectively, for the baked membrane.
Atomic simulation of SiC etching by energetic SiF3
Authors: Gou F. , Chuanliang Meng , Lingzhouting Chen , Qian Qiu
Published: July 2007

The authors present results from molecular-dynamics simulations of SiF3 impact on SiC (100) surfaces at normal incidence and over a range of energies of 10, 50, and 150eV. The surface temperatures are set to 300K for all energies and 600K for 150eV. The uptake of Si atoms is sensitive to the incident energy and temperature, while the uptake of F atoms is not very sensitive to the incident energy and temperature. The simulation results show that the etching yield of Si is higher than that of C. After 30 ML (monolayers) fluence, SiF3 does not etch SiC. The F-containing reaction layer is sensitive to the incident energy. The thickness of the reaction layer increases with the incident energy. In the reaction layer, SiF, SiF2, CF, and CF2 species are dominant. In etch products, atomic F etch products are dominant. Si atoms in SiC are mainly sputtered as SiFx (x=1–4). C atoms in SiC are sputtered as larger SixCyFZ species.
Preparation and photocatalytic activity of TiOxNy∕CdS heterojunctions
Authors: Prabakar K. , Takahashi T. , Nezuka T. , Takahashi K. , Nakashima T. , Kubota Y. , Fujishima A.
Published: July 2007

Nitrogen doped titanium oxide (TiOxNy) thin films were deposited by facing-target sputtering on glass substrates at different nitrogen flow rates (NR) of 0, 5, 10, 15, and 20SCCM (SCCM denotes cubic centimeter per minute at STP) at a fixed sputtering pressure of 0.8Pa to identify the optimum dopant concentration for the efficient photocatalytic activity. X-ray diffraction experiments revealed that the films have anatase phase until NR of 10SCCM and become amorphous with further increase in NR. Higher level nitrogen doping is inhibited due to the difficulty in the replacement of oxygen. CdS thin films were deposited by chemical bath deposition method using the CdCl2 and thiourea as the precursors, and NH3NO4 and KOH as the complexing agent have the optical band gaps of 2.38–2.5eV for the different thiourea solution concentrations and hexagonal structures. The photocatalytic decomposition of methanol proceeds via formaldehyde and CO as the intermediate species and CO2 is produced after the complete decomposition. The optimum NR for the nitrogen doping in TiO2 films were found be 5SCCM. The properties of the films, including the crystallinity, surface morphology, and light absorption capability, are influenced by the nitrogen flow rate, whereas the photocatalytic reaction on TiOxNy thin films is very sensitive to crystallinity and its surface structure.
Electrical properties of organic light-emitting diodes by indium tin oxide chemical-mechanical polishing process
Authors: Choi Gwon-Woo , Seo Yong-Jin , Lee Kang-Yeon , Lee Woo-Sun
Published: July 2007

In this study, the optimum process parameters and the influences of their process parameters were investigated for indium tin oxide chemical-mechanical polishing (ITO-CMP) with a sufficient removal amount and good planarity. Next, the organic light-emitting display (OLED) device with the structure of glass∕ITO∕poly[2-methoxy-5-(2-ethylhexyloxy)-p-phenylenevinylene]∕Al using a polished ITO surface as a bottom electrode (anode) was fabricated. The electrical characteristics, such as sheet resistance and current-voltage (I-V) relationship, are discussed in order to evaluate the possibility of the CMP application for an OLED device using an ITO film. The surface morphology and I-V characteristics of ITO thin film were improved after the CMP process using optimized process parameters compared to that of the as-deposited thin film before the CMP process.
B-doped Be coatings for NIF target development
Authors: Xu H. , Moreno K. A. , Youngblood K. P. , Nikroo A. , Hackenberg R. E. , Cooley J. C. , Alford C. S. , Letts S. A.
Published: July 2007

Sputtered beryllium and copper-doped beryllium coatings as thick as 170μm have been deposited on spherical substrates to produce hollow shells that are required as targets for inertial fusion experiments. Be coatings by magnetron sputtering achieved ∼95±2% bulk density consistently up to 170μm thick. Coatings on the spherical substrates exhibit the typical columnar structure throughout the entire thickness. Transmission electron microscopy indicates the presence of submicron, nearly spherical voids mainly aggregated along the columnar structure and grain boundaries, as well as some smaller intragranular elongated voids. Holes have been drilled in beryllium shells produced in this manner to allow filling with deuterium (the fusion fuel). Gas retention of these shells has been examined using mass spectrometry. It appears that a fraction of the pores in the coatings are interconnected, which leads to leakage of the hollow shells. Boron-doped Be layers near the eutectic phase, at a concentration of ∼11at.%, have been added to the Be shells to significantly improve D2 gas retention of the shells. However, there remains a considerable scatter in the measured leakage.
Structure and chemical properties of molybdenum oxide thin films
Authors: Ramana C. V. , Atuchin V. V. , Pokrovsky L. D. , Becker U. , Julien C. M.
Published: July 2007

Molybdenum oxide (MoO3) exhibits interesting structural, chemical, electrical, and optical properties, which are dependent on the growth conditions and the fabrication technique. In the present work, MoO3 films were produced by pulsed-laser deposition and dc magnetron sputtering under varying conditions of growth temperature (Ts) and oxygen pressure (pO2). The effect of growth conditions on the structure and chemical properties of MoO3 films was examined using x-ray diffraction, reflection high-energy electron diffraction, x-ray photoelectron spectroscopy, and infrared spectroscopic measurements. The analyses indicate that the microstructure of Mo oxide films is sensitive to Ts and pO2. The growth conditions were optimized to produce stoichiometric and highly textured polycrystalline MoO3 films. A comparison of the microstructure of MoO3 films grown using pulsed-laser deposition and sputtering methods is also presented.
Impact of etching kinetics on the roughening of thermal SiO2 and low-k dielectric coral films in fluorocarbon plasmas
Authors: Yin Yunpeng , Sawin Herbert H.
Published: July 2007

The impact of etching kinetics and etching chemistries on surface roughening was investigated by etching thermal silicon dioxide and low-k dielectric coral materials in C4F8∕Ar plasma beams in an inductive coupled plasma beam reactor. The etching kinetics, especially the angular etching yield curves, were measured by changing the plasma pressure and the feed gas composition which influence the effective neutral-to-ion flux ratio during etching. At low neutral-to-ion flux ratios, the angular etching yield curves are sputteringlike, with a peak around 60°–70° off-normal angles; the surface at grazing ion incidence angles becomes roughened due to ion scattering related ion-channeling effects. At high neutral-to-ion flux ratios, ion enhanced etching dominates and surface roughening at grazing angles is mainly caused by the local fluorocarbon deposition induced micromasking mechanism. Interestingly, the etched surfaces at grazing angles remain smooth for both films at intermediate neutral-to-ion flux ratio regime. Furthermore, the oxygen addition broadens the region over which the etching without roughening can be performed.
Large-area pulsed-laser deposition of dielectric and ferroelectric thin films
Authors: Sakai Shigeki , Takahashi Mitsue , Motohashi Kennichi , Yamaguchi Yuji , Yui Naomasa , Kobayashi Takichi
Published: July 2007

The authors have developed a large-area pulsed-laser deposition (PLD) technique, suited in particular for depositing high-k dielectric and ferroelectric thin films of high quality on Si wafers of 8in. diameter. By using this technique, 42- and 6-nm-thick HfO2 films were deposited on 8 and 6in. Si wafers at room temperature, respectively. The standard deviations of thickness were 1.3% and 1.6% of their respective means. Cross-sectional transmission-electron microscopy pictures of the 6-nm-thick HfO2 film on Si showed that an interfacial layer between HfO2 and Si was thinner than 1nm. In order to measure the electrical properties, Pt top electrodes were deposited on the HfO2 film and the Al bottom electrode was deposited on the Si. Capacitance-voltage measurements of the Pt∕HfO2∕Si showed that the standard deviation of capacitances was as small as 1.9%. A ferroelectric SrBi2Ta2O9 (SBT) film was also deposited on a 4in. Si wafer at 400°C using the large-area PLD technique. The standard deviation of the SBT film thickness was 1.2% of 94nm, the average thickness. The large-area PLD technique the authors developed can meet the industrial needs for high and uniform quality over large-area high-k dielectric and/or ferroelectric thin films for large-scale integrated circuits.
Transparent conducting Al-doped ZnO thin films prepared by magnetron sputtering with dc and rf powers applied in combination
Authors: Minami Tadatsugu , Ohtani Yuusuke , Miyata Toshihiro , Kuboi Takeshi
Published: July 2007

A newly developed Al-doped ZnO (AZO) thin-film magnetron-sputtering deposition technique that decreases resistivity, improves resistivity distribution, and produces high-rate depositions has been demonstrated by dc magnetron-sputtering depositions that incorporate rf power (dc+rf-MS), either with or without the introduction of H2 gas into the deposition chamber. The dc+rf-MS preparations were carried out in a pure Ar or an Ar+H2 (0%–2%) gas atmosphere at a pressure of 0.4Pa by adding a rf component (13.56MHz) to a constant dc power of 80W. The deposition rate in a dc+rf-MS deposition incorporating a rf power of 150W was approximately 62nm∕min, an increase from the approximately 35nm∕min observed in dc magnetron sputtering with a dc power of 80W. A resistivity as low as 3×10−4Ωcm and an improved resistivity distribution could be obtained in AZO thin films deposited on substrates at a low temperature of 150°C by dc+rf-MS with the introduction of hydrogen gas with a content of 1.5%. This article describes the effects of adding a rf power component (i.e., dc+rf-MS deposition) as well as introducing H2 gas into dc magnetron-sputtering preparations of transparent conducting AZO thin films.
In Vitro Susceptibilities of
Mycoplasma putrefaciens
Field Isolates
Authors: Antunes N. T. , Tavío M. M. , Mercier P. , Ayling R. D. , Al-Momani W. , Assunção P. , Rosales R. S. , Poveda J. B.
Published: July 2007

MICs were determined for 15 antimicrobial agents against 37
Mycoplasma putrefaciens
isolates. The most effective antimicrobial drug classes were the fluoroquinolones, the tetracyclines, the lincosamide lincomycin, and the macrolides. The susceptibility profile of the isolates correlated with the geographic origin. This is the first report of decreased susceptibility to the macrolides, lincomycin, and the tetracyclines in
M. putrefaciens
strains.
Intermittent Preventive Treatment in Infants as a Means of Malaria Control: a Randomized, Double-Blind, Placebo-Controlled Trial in Northern Ghana
Authors: Mockenhaupt Frank P. , Reither Klaus , Zanger Philipp , Roepcke Felix , Danquah Ina , Saad Eiman , Ziniel Peter , Dzisi Stephen Y. , Frempong Marc , Agana-Nsiire Patrick , Amoo-Sakyi Felicia , Otchwemah Rowland , Cramer Jakob P. , Anemana Sylvester D. , Dietz Ekkehart , Bienzle Ulrich
Published: July 2007

Morbidity and mortality from malaria remain unacceptably high among young children in sub-Saharan Africa. Intermittent preventive treatment in infancy (IPTi) involves the administration of antimalarials alongside routine vaccinations and might be an option in malaria control. In an area of intense, perennial malaria transmission in northern Ghana, 1,200 children received IPTi with sulfadoxine-pyrimethamine or placebo at approximately 3, 9, and 15 months of age. Children were followed up until 24 months of age to assess morbidity and adverse events. During the intervention period (3 to 18 months of age), IPTi reduced the incidences of malaria and severe anemia by 22.5% (95% confidence interval, 12 to 32%) and 23.6% (95% confidence interval, 4 to 39%), respectively, and reduced hospitalizations and episodes of asymptomatic parasitemia by one-third. Protection was pronounced in the first year of life and not discernible in the second. The malaria-protective effect was largely confined to a period of 1 month after sulfadoxine-pyrimethamine treatments. Following the intervention, protection against asymptomatic parasitemia persisted. In contrast, a significant rebound of severe malaria, predominantly severe malarial anemia, occurred among children having received IPTi. Although the treatment was generally well tolerated, one case of moderately severe skin reaction followed sulfadoxine-pyrimethamine treatment. IPTi reduces malaria and anemia in infants in northern Ghana. Extension of IPTi into the second year of life by administering a dose at 15 months of age provided no substantial benefit beyond a 1-month prophylactic effect. Although this simple intervention offers one of the few available malaria-preventive measures for regions where malaria is endemic, the observed rebound of severe malaria advises caution and requires further investigation.
Impact of Dual Infections on Chemotherapeutic Efficacy in BALB/c Mice Infected with Major Genotypes ofTrypanosoma cruzi
Authors: Martins H. R. , Silva R. Moreira , Valadares H. M. S. , Toledo M. J. O. , Veloso V. M. , Vitelli-Avelar D. M. , Carneiro C. M. , Machado-Coelho G. L. L. , Bahia M. T. , Martins-Filho O. A. , Macedo A. M. , Lana M.
Published: July 2007

The aim of this work was to investigate the impact of dual infections with stocks ofTrypanosoma cruzimajor genotypes on benznidazole (BZ) treatment efficacy. For this purpose,T. cruzistocks representative of the geneticT. cruzilineages, displaying different susceptibilities to BZ, belonging to the majorT. cruzigenotypes broadly dispersed in North and South America and important in Chagas’ disease epidemiology were used. Therapeutic efficacy was observed in 27.8% of the animals treated. Following BZ susceptibility classification, significant differences were observed in dual infections on the major genotype level, demonstrating that combinations of genotypes 19+39 and genotypes 19+32 led to a shift in the expected BZ susceptibility profile toward the resistance pattern. Analysis on theT. cruzistock level demonstrated that 9 out of 24 dual infections shifted the expected BZ susceptibility profile compared with the respective single infections, including shifts toward lower and higher BZ susceptibilities. Microsatellite identification was able to identify a mixture ofT. cruzistocks in 7.7% of theT. cruziisolates from infected and untreated mice (6.9%) and infected and treated but not cured mice (9.0%), revealing in some mixtures of BZ-susceptible and -resistant stocks that theT. cruzistock identified after BZ treatment was previously susceptible in single infections. Considering the clonal structure and evolution ofT. cruzi, an unexpected result was the identification of parasite subpopulations with distinct microsatellite alleles in relation to the original stocks observed in 12.2% of the isolates. Taken together, the data suggest that mixed infections, already verified in nature, may have an important impact on the efficacy of chemotherapy.
Interaction between Leukotoxin and Cu,Zn Superoxide Dismutase in
Aggregatibacter actinomycetemcomitans
Authors: Balashova Nataliya V. , Park Diane H. , Patel Jigna K. , Figurski David H. , Kachlany Scott C.
Published: July 2007

Aggregatibacter
(
Actinobacillus
)
actinomycetemcomitans
is a gram-negative oral pathogen that is the etiologic agent of localized aggressive periodontitis and systemic infections.
A. actinomycetemcomitans
produces leukotoxin (LtxA), which is a member of the RTX (repeats in toxin) family of secreted bacterial toxins and is known to target human leukocytes and erythrocytes. To better understand how LtxA functions as a virulence factor, we sought to detect and study potential
A. actinomycetemcomitans
proteins that interact with LtxA. We found that Cu,Zn superoxide dismutase (SOD) interacts specifically with LtxA. Cu,Zn SOD was purified from
A. actinomycetemcomitans
to homogeneity and remained enzymatically active. Purified Cu,Zn SOD allowed us to isolate highly specific anti-Cu,Zn SOD antibody and this antibody was used to further confirm protein interaction. Cu,Zn SOD-deficient mutants displayed decreased survival in the presence of reactive oxygen and nitrogen species and could be complemented with wild-type Cu,Zn SOD in
trans
. We suggest that
A. actinomycetemcomitans
Cu,Zn SOD may protect both bacteria and LtxA from reactive species produced by host inflammatory cells during disease. This is the first example of a protein-protein interaction involving a bacterial Cu,Zn SOD.
Human CD18 Is the Functional Receptor forAggregatibacter actinomycetemcomitansLeukotoxin
Authors: Dileepan T. , Kachlany S. C. , Balashova N. V. , Patel J. , Maheswaran S. K.
Published: July 2007

Aggregatibacter(Actinobacillus)actinomycetemcomitansis the causative organism of localized aggressive periodontitis, a rapidly progressing degenerative disease of the gingival and periodontal ligaments, and is also implicated in causing subacute infective endocarditis in humans. The bacterium produces a variety of virulence factors, including an exotoxic leukotoxin (LtxA) that is a member of the repeats-in-toxin (RTX) family of bacterial cytolysins. LtxA exhibits a unique specificity to macrophages and polymorphonuclear cells of humans and other primates. Human lymphocyte function-associated antigen 1 (LFA-1) has been implicated as the putative receptor for LtxA. Human LFA-1 comprises the CD11a and CD18 subunits. It is not clear, however, which of its subunits serves as the functional receptor that confers species-specific susceptibility to LtxA. Here we demonstrate that the human CD18 is the receptor for LtxA based on experiments performed with chimeric β2-integrins recombinantly expressed in a cell line that is resistant to LtxA effects. In addition, we show that the cysteine-rich tandem repeats encompassing integrin-epidermal growth factor-like domains 2, 3, and 4 of the extracellular region of human CD18 are critical for conferring susceptibility to LtxA-induced biological effects.
σ
B
and the σ
B
-Dependent
arlRS
and
yabJ-spoVG
Loci Affect Capsule Formation in
Staphylococcus aureus
Authors: Meier Stefan , Goerke Christiane , Wolz Christiane , Seidl Kati , Homerova Dagmar , Schulthess Bettina , Kormanec Jan , Berger-Bächi Brigitte , Bischoff Markus
Published: July 2007

The alternative transcription factor σ
B
of
Staphylococcus aureus
affects the transcription of the
cap
gene cluster, required for the synthesis of capsular polysaccharide (CP), although this operon is lacking an apparent σ
B
-dependent promoter. Regulation of
cap
expression and CP production in
S. aureus
strain Newman was shown here to be influenced by σ
B
, the two-component signal transduction regulatory system ArlRS, and the
yabJ-spoVG
locus to different extents. Inactivation of
arlR
or deletion of the
sigB
operon strongly suppressed
capA
(CP synthesis enzyme A) transcription. Deletion of
spoVG
had a polar effect on
yabJ-spoVG
transcription and resulted in a two- to threefold decrease in
capA
transcription. Interestingly, immunofluorescence showed that CP production was strongly impaired in all three mutants, signaling that the
yabJ-spoVG
inactivation, despite its only partial effect on
capA
transcription, abolished capsule formation.
trans
-Complementation of the Δ
spoVG
mutant with
yabJ-spoVG
under the control of its native promoter restored CP-5 production and
capA
expression to levels seen in the wild type. Northern analyses revealed a strong impact of σ
B
on
arlRS
and
yabJ-spoVG
transcription. We hypothesize that ArlR and products of the
yabJ-spoVG
locus may serve as effectors that modulate σ
B
control over σ
B
-dependent genes lacking an apparent σ
B
promoter.
DYNAMIC MEMORIZATION CHARACTERISTICS IN NEURAL NETWORKS WITH DIFFERENT NEURONAL DYNAMICS
Authors: KATADA NAOFUMI , NISHIMURA HARUHIKO
Published: July 2007

We introduce a stimulus-response scheme that supports plastic variation of synapse weights in neural networks, and analyze how memory formation evolves under external stimulation. In so doing, chaotic networks and stochastic networks that have very different dynamics are compared. Experimental results suggest that chaotic activity remarkably outperforms stochastic activity in stimulus-response memorization. This seems to be indicative of effectiveness of the chaos in dynamic learning by stimulus-response scheme oriented to natural learning.
BIOMECHANICAL STABILITY ANALYSIS OF THE λ-MODEL CONTROLLING ONE JOINT
Authors: LAN L. , ZHU K. Y.
Published: July 2007

Computer modeling and control of the human motor system might be helpful for understanding the mechanism of human motor system and for the diagnosis and treatment of neuromuscular disorders. In this paper, a brief view of the equilibrium point hypothesis for human motor system modeling is given, and the λ-model derived from this hypothesis is studied. The stability of the λ-model based on equilibrium and Jacobian matrix is investigated. The results obtained in this paper suggest that the λ-model is stable and has a unique equilibrium point under certain conditions.
DELAY-DEPENDENT ROBUST EXPONENTIAL STABILITY FOR UNCERTAIN RECURRENT NEURAL NETWORKS WITH TIME-VARYING DELAYS
Authors: ZHANG BAOYONG , XU SHENGYUAN , LI YONGMIN
Published: July 2007

This paper considers the problem of robust exponential stability for a class of recurrent neural networks with time-varying delays and parameter uncertainties. The time delays are not necessarily differentiable and the uncertainties are assumed to be time-varying but norm-bounded. Sufficient conditions, which guarantee that the concerned uncertain delayed neural network is robustly, globally, exponentially stable for all admissible parameter uncertainties, are obtained under a weak assumption on the neuron activation functions. These conditions are dependent on the size of the time delay and expressed in terms of linear matrix inequalities. Numerical examples are provided to demonstrate the effectiveness and less conservatism of the proposed stability results.
LIFTS OF SYMPLECTIC DIFFEOMORPHISMS AS AUTOMORPHISMS OF A WEYL ALGEBRA BUNDLE WITH FEDOSOV CONNECTION
Authors: MIYAZAKI NAOYA
Published: July 2007

In the present paper, we are concerned with lifts of symplectic diffeomorphisms as automorphisms of star product. We also study a regular Lie group structure (cf. [14, 20, 21]) of the group of automorphisms of star product on a symplectic manifold.
HOPF ALGEBRAS IN DYNAMICAL SYSTEMS THEORY
Authors: CARIÑENA JOSÉ F. , EBRAHIMI-FARD KURUSCH , FIGUEROA HÉCTOR , GRACIA-BOND JOSÉ M.
Published: July 2007

The theory of exact and of approximate solutions for non-autonomous linear differential equations forms a wide field with strong ties to physics and applied problems. This paper is meant as a stepping stone for an exploration of this long-established theme, through the tinted glasses of a (Hopf and Rota–Baxter) algebraic point of view. By reviewing, reformulating and strengthening known results, we give evidence for the claim that the use of Hopf algebra allows for a refined analysis of differential equations. We revisit the renowned Campbell–Baker–Hausdorff–Dynkin formula by the modern approach involving Lie idempotents. Approximate solutions to differential equations involve, on the one hand, series of iterated integrals solving the corresponding integral equations; on the other hand, exponential solutions. Equating those solutions yields identities among products of iterated Riemann integrals. Now, the Riemann integral satisfies the integration-by-parts rule with the Leibniz rule for derivations as its partner; and skewderivations generalize derivations. Thus, we seek an algebraic theory of integration, with the Rota–Baxter relation replacing the classical rule. The methods to deal with noncommutativity are especially highlighted. We find new identities, allowing for an extensive embedding of Dyson–Chen series of time- or path-ordered products (of generalized integration operators); of the corresponding Magnus expansion; and of their relations, into the unified algebraic setting of Rota–Baxter maps and their inverse skewderivations. This picture clarifies the approximate solutions to generalized integral equations corresponding to non-autonomous linear (skew) differential equations.
Electron Holography: Phase Imaging with Nanometer Resolution
Authors: McCartney Martha R. , Smith David J.
Published: July 2007

Electron holography provides a unique phase-imaging approach for characterizing nanoscale electrostatic and magnetic fields. From the relative phase shifts of the electron wave that has passed through the sample, quantitative field measurements that can be related back to specific features of the object can be made. The basic theory and experimental geometry for the off-axis mode of electron holography are first presented. Representative studies over a wide range of materials are then described. Applications involving electrostatic fields include p-n junctions and dopant profiles, piezoelectric fields and ferroelectrics, and charged defects and boundaries. Applications involving magnetic materials include hard magnets, thin films, and nanostructures, both man-made and naturally occurring. Finally, prospects for future developments and applications are briefly discussed.
Ferroelectric Epitaxial Thin Films for Integrated Optics
Authors: Wessels Bruce W.
Published: July 2007

Thin film ferroelectrics are being developed for integrated optics applications. Their major advantage lies in their large electro-optic coefficients. Furthermore, they are nearly transparent from the mid-infrared to the visible spectral region. With the development of epitaxial deposition techniques for ferroelectrics, waveguide structures with low optical loss have been demonstrated. Through the use of epitaxial thin films deposited on low-index substrates, high-bandwidth electro-optic modulators have also been attained.
Defect–Domain Wall Interactions in Trigonal Ferroelectrics
Authors: Gopalan Venkatraman , Dierolf Volkmar , Scrymgeour David A.
Published: July 2007

Domains and domain walls are a fundamental property of interest in ferroelectrics, magnetism, ferroelastics, superconductors, and multiferroic materials. Unlike magnetic Bloch walls, ideal ferroelectric domain walls are well accepted to be only one to two lattice units wide, over which polarization and strain change across the wall. However, walls in real ferroelectrics appear to show unexpected property variations in the vicinity of domain walls that can extend over micrometer length scales. This chapter specifically reviews the local electrical, elastic, optical, and structural properties of antiparallel domain walls in the trigonal ferroelectrics lithium niobate and lithium tantalate. It is shown that extrinsic point defects and their clustering play a key role in the observed local wall structure and influence macroscale properties by orders of magnitude. The review also raises broader and yet unexplored fundamental questions regarding intrinsic widths, defect–domain wall interactions, and static versus dynamic wall structure.
Maternal vitamin A alters gene profiles and structural maturation of the rat ductus arteriosus
Authors: Yokoyama Utako , Sato Yoji , Akaike Toru , Ishida Seiichi , Sawada Junichi , Nagao Taku , Quan Hong , Jin Meihua , Iwamoto Mari , Yokota Shumpei , Ishikawa Yoshihiro , Minamisawa Susumu
Published: July 2007

Retinoic acid (RA), a metabolite of vitamin A, has been proposed to regulate vascular remodeling and reactivity of the ductus arteriosus (DA). Using rat Affymetrix GeneChips, we found that a considerable number of genes in DA varied their expression levels in accordance with developmental mode: namely, preterm-, term-, and postnatal-dominant clusters. Among a total of 8,740 probe sets, maternal vitamin A administration (MVA) changed the expression levels of 91 genes (116 probe sets) >2.5-fold. About half of preterm- and term-dominant genes responded to MVA, whereas only 5% of postnatal-dominant genes responded to MVA, indicating that fetal-dominant genes were susceptible to RA signals. The expression levels of 51 genes in MVA-treated DA at preterm were similar to the expression levels in nontreated DA at term, indicating that the global gene profile at preterm resembled that of the control animal at term. We observed neointima formation in MVA-treated DA at preterm in accordance with upregulation of fibronectin and hyaluronic acid, whereas it was rarely observed in nontreated DA at preterm. Five fetal cardiac myofibrillar genes were also upregulated in MVA-treated in vivo DA, whereas they were developmentally downregulated in nontreated DA. The present study indicates that MVA-mediated alteration in gene profile was associated with early structural maturation of DA, although MVA-mediated maturation may differ from normal vascular remodeling of DA.
The PAX3-FKHR Fusion Gene of Rhabdomyosarcoma Cooperates with Loss of p16INK4A to Promote Bypass of Cellular Senescence
Authors: Linardic Corinne M. , Naini Sarasija , Herndon James E. , Kesserwan Chimen , Qualman Stephen J. , Counter Christopher M.
Published: July 2007

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histologic variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of <30%. ARMS is characterized by a chromosomal translocation generating the PAX3-FKHR fusion gene. However, ectopic expression of PAX3-FKHR often induces inhibition of cell proliferation, or cell death, when expressed in nonmuscle cells. This prompted us to explore the effect of expressing PAX3-FKHR in more relevant cells, specifically primary human skeletal muscle cells because these cells can be converted to a tumorigenic state that mimics rhabdomyosarcoma. PAX3-FKHR expression promoted both fetal and postnatal primary human skeletal muscle cell precursors to bypass the senescence growth arrest checkpoint. This bypass was accompanied by epigenetic DNA methylation of the p16INK4A promoter and correspondingly a loss of expression of this tumor suppressor. Knockdown of p16INK4A cooperated with PAX3-FKHR to drive proliferation past senescence, whereas reintroduction of wild-type p16INK4A in post-senescent cells caused growth arrest. Thus, PAX3-FKHR acts in concert with loss of p16INK4A to promote inappropriate proliferation of skeletal muscle cells. This association between PAX3-FKHR expression and p16INK4A loss was seen in human ARMS tumor tissue, as both human rhabdomyosarcoma cell lines and tissue microarrays showed a trend toward down-regulation of p16INK4A protein in alveolar subsets. We surmise that the generation of the PAX3-FKHR fusion protein may require loss of p16INK4A to promote malignant proliferation of skeletal muscle cells as an early step in ARMS tumorigenesis. [Cancer Res 2007;67(14):6691–9]
IRE1 Signaling Is Essential for Ischemia-Induced Vascular Endothelial Growth Factor-A Expression and Contributes to Angiogenesis and Tumor Growth In vivo
Authors: Drogat Benjamin , Auguste Patrick , Nguyen Duc Thang , Bouchecareilh Marion , Pineau Raphael , Nalbantoglu Josephine , Kaufman Randal J. , Chevet Eric , Bikfalvi Andréas , Moenner Michel
Published: July 2007

In solid tumors, cancer cells subjected to ischemic conditions trigger distinct signaling pathways contributing to angiogenic stimulation and tumor development. Characteristic features of tumor ischemia include hypoxia and glucose deprivation, leading to the activation of hypoxia-inducible factor-1–dependent signaling pathways and to complex signaling events known as the unfolded protein response. Here, we show that the activation of the endoplasmic reticulum stress sensor IRE1 is a common determinant linking hypoxia- and hypoglycemia-dependent responses to the up-regulation of vascular endothelial growth factor-A (VEGF-A). Tumor cells expressing a dominant-negative IRE1 transgene as well as Ire1α-null mouse embryonic fibroblasts were unable to trigger VEGF-A up-regulation upon either oxygen or glucose deprivation. These data correlated with a reduction of tumor angiogenesis and growth in vivo. Our results therefore suggest an essential role for IRE1-dependent signaling pathways in response to ischemia and identify this protein as a potential therapeutic target to control both the angiogenic switch and tumor development. [Cancer Res 2007;67(14):6700–7]
Targeted Cancer Gene Therapy Using a Hypoxia Inducible Factor–Dependent Oncolytic Adenovirus Armed with Interleukin-4
Authors: Post Dawn E. , Sandberg Eric M. , Kyle Michele M. , Devi Narra Sarojini , Brat Daniel J. , Xu Zhiheng , Tighiouart Mourad , Van Meir Erwin G.
Published: July 2007

There is a need for novel therapies targeting hypoxic cells in tumors. These cells are associated with tumor resistance to therapy and express hypoxia inducible factor-1 (HIF-1), a transcription factor that mediates metabolic adaptation to hypoxia and activates tumor angiogenesis. We previously developed an oncolytic adenovirus (HYPR-Ad) for the specific killing of hypoxic/HIF-active tumor cells, which we now armed with an interleukin-4 gene (HYPR-Ad-IL4). We designed HYPR-Ad-IL4 by cloning the Ad E1A viral replication and IL-4 genes under the regulation of a bidirectional hypoxia/HIF-responsive promoter. The IL-4 cytokine was chosen for its ability to induce a strong host antitumor immune response and its potential antiangiogenic activity. HYPR-Ad-IL4 induced hypoxia-dependent IL-4 expression, viral replication, and conditional cytolysis of hypoxic, but not normoxic cells. The treatment of established human tumor xenografts with HYPR-Ad-IL4 resulted in rapid and maintained tumor regression with the same potency as that of wild-type dl309-Ad. HYPR-Ad-IL4–treated tumors displayed extensive necrosis, fibrosis, and widespread viral replication. Additionally, these tumors contained a distinctive leukocyte infiltrate and prominent hypoxia. The use of an oncolytic Ad that locally delivers IL-4 to tumors is novel, and we expect that HYPR-Ad-IL4 will have broad therapeutic use for all solid tumors that have hypoxia or active HIF, regardless of tissue origin or genetic alterations. [Cancer Res 2007;67(14):6872–81]
Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth
Authors: Buzzai Monica , Jones Russell G. , Amaravadi Ravi K. , Lum Julian J. , DeBerardinis Ralph J. , Zhao Fangping , Viollet Benoit , Thompson Craig B.
Published: July 2007

The effect of the antidiabetic drug metformin on tumor growth was investigated using the paired isogenic colon cancer cell lines HCT116 p53+/+ and HCT116 p53−/−. Treatment with metformin selectively suppressed the tumor growth of HCT116 p53−/− xenografts. Following treatment with metformin, we detected increased apoptosis in p53−/− tumor sections and an enhanced susceptibility of p53−/− cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin is proposed to function in diabetes treatment as an indirect activator of AMP-activated protein kinase (AMPK). Treatment with AICAR, another AMPK activator, also showed a selective ability to inhibit p53−/− tumor growth in vivo. In the presence of either of the two drugs, HCT116 p53+/+ cells, but not HCT116 p53−/− cells, activated autophagy. A similar p53-dependent induction of autophagy was observed when nontransformed mouse embryo fibroblasts were treated. Treatment with either metformin or AICAR also led to enhanced fatty acid β-oxidation in p53+/+ MEFs, but not in p53−/− MEFs. However, the magnitude of induction was significantly lower in metformin-treated cells, as metformin treatment also suppressed mitochondrial electron transport. Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner. Together, these data suggest that metformin treatment forces a metabolic conversion that p53−/− cells are unable to execute. Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin. [Cancer Res 2007;67(14):6745–52]
ERM/ETV5 Up-regulation Plays a Role during Myometrial Infiltration through Matrix Metalloproteinase-2 Activation in Endometrial Cancer
Authors: Monge Marta , Colas Eva , Doll Andreas , Gonzalez Marta , Gil-Moreno Antonio , Planaguma Jesus , Quiles Maite , Arbos Maria Antonia , Garcia Angel , Castellvi Josep , Llaurado Marta , Rigau Marina , Alazzouzi Hafid , Xercavins Jordi , Alameda Francesc , Reventos Jaume , Abal Miguel
Published: July 2007

We have described recently the Ets family transcription factor, ERM/ETV5, specifically up-regulated in endometrioid endometrial carcinoma (EEC) and associated with myometrial infiltration. Ets family members have been correlated to tumor progression by up-regulating the expression of matrix-degrading proteases. In the present study, we investigated the possibility that in EEC, ERM/ETV5 may act by inducing the expression of genes involved in extracellular matrix remodeling. Unraveling the molecular events associated with the initiation of tumor invasion would represent an obvious improvement for EEC patients. The overexpression of ERM/ETV5 induced scattering in the endometrial cancer cell line Hec-1A, correlating to increased matrix metalloproteinase-2 (MMP-2) gelatinase activity. Both chromatin immunoprecipitation and reversion experiments with RNA interference and specific MMP-2 inhibitor showed a functional link between ERM/ETV5 overexpression and MMP-2 activation. The increased MMP-2 activity associated with overexpressed ERM/ETV5 in a mouse model conferred invasive capacity to endometrial tumors. Orthotopically implanted overexpressing ERM/ETV5 tumors presented a more aggressive and infiltrative pattern of myometrial invasion. Finally, the specific localization of ERM/ETV5 and MMP-2 at the invasive front of myometrial infiltrating human endometrial carcinomas further reinforced the hypothesis of a role for ERM/ETV5 in the early steps of endometrial dissemination. Taken together, these results lead us to propose that in EEC, ERM/ETV5 acts through MMP-2 gelatinolytic activity to confer invasive capabilities, associated with an initial switch to myometrial infiltration. They also postulate ERM/ETV5 as a valuable marker for patient stratification and a transcription pathway that should be evaluated for therapies specifically targeting the initial steps of EEC dissemination. [Cancer Res 2007;67(14):6753–9]
Discovery and Validation of Biomarkers that Respond to Treatment with Brivanib Alaninate, a Small-Molecule VEGFR-2/FGFR-1 Antagonist
Authors: Ayers Mark , Fargnoli Joseph , Lewin Anne , Wu Qiuyan , Platero J. Suso
Published: July 2007

The process of neovascularization from preexisting blood vessels, referred to as angiogenesis, plays a critical role in both tumor growth and dissemination in multiple cancer types. Currently, there exists a need to identify biomarkers that can both indicate biological activity and predict efficacy at the molecular level for antiangiogenesis drugs which are anticipated to result in tumor stasis rather than regression. To identify such biomarkers, athymic mice bearing L2987 human tumor xenografts were treated with the antiangiogenic agent brivanib alaninate, which is currently under clinical evaluation. This is an orally available and selective tyrosine kinase inhibitor that targets the key angiogenesis receptors vascular endothelial growth factor receptor 2 (VEGFR-2) and fibroblast growth factor receptor 1. In the described studies, tumor samples were collected from these xenografts and RNA was extracted for gene expression profiling on Affymetrix 430A mouse GeneChips. Statistical analysis was done using a defined set of genes identified to be coexpressed with VEGFR-2 from a clinical tumor gene expression profiling database and between tumor samples isolated from brivanib alaninate–treated and untreated mice. Tyrosine kinase receptor 1 (Tie-1), collagen type IV α1 (Col4a1), complement component 1, q subcomponent receptor 1 (C1qr1), angiotensin receptor–like 1 (Agtrl1), and vascular endothelial-cadherin (Cdh5) were all identified to be significantly modulated by treatment with brivanib alaninate. These genes, which may be potentially useful as markers of brivanib alaninate activity, were further studied at the protein level in two separate in vivo human colon tumor xenograft models, HCT116 and GEO, using immunohistochemistry-based approaches. [Cancer Res 2007;67(14):6899–906]