bluuebunny/crossref_metadata_2025 huggingface dataset:
MICZ-Kepler problems in all dimensions
Authors: Meng Guowu
Published: March 2007

The Kepler problem is a physical problem about two bodies which attract each other by a force proportional to the inverse square of the distance. The MICZ-Kepler problems are its natural cousins and have been previously generalized from dimension 3 to dimension 5. In this paper, we construct and analyze the (quantum) MICZ-Kepler problems in all dimensions higher than 2.
Microstructure of Mn-doped γ-Ga2O3 epitaxial film on sapphire (0001) with room temperature ferromagnetism
Authors: Huang Rong , Hayashi Hiroyuki , Oba Fumiyasu , Tanaka Isao
Published: March 2007

Mn-doped Ga2O3 thin film showing room temperature ferromagnetism has been grown on a sapphire (0001) plane by using a pulsed-laser deposition technique. The microstructure of the Mn-doped film is investigated in detail using selected-area electron diffraction, high-resolution transmission electron microscopy (HRTEM), x-ray energy-dispersive spectroscopy, and electron energy-loss spectroscopy, in comparison with an undoped film. Careful diffraction analysis with the [21¯1¯0]Al2O3 and [101¯0]Al2O3 zone axes of the substrates reveals that the Mn-doped film shows the γ-Ga2O3 phase with a defective spinel structure, while the undoped film shows the β-Ga2O3 phase. The orientation relationship between the film and substrate is determined by electron diffraction and HRTEM from the interface region to be (2¯01)β-Ga2O3∕∕(0001)Al2O3 and [102]β-Ga2O3∕∕[21¯1¯0]Al2O3 or [1¯02¯]β-Ga2O3∕∕[21¯1¯0]Al2O3 for the undoped film, and (111)γ-Ga2O3∕∕(0001)Al2O3 and [21¯1¯]γ-Ga2O3∕∕[21¯1¯0]Al2O3 or [2¯11]γ-Ga2O3∕∕[21¯1¯0]Al2O3 for the Mn-doped film. Mn ions are uniformly dissolved in the film with 7.8 cation % and no detectable precipitates are found. Mn-L2, 3 energy-loss near-edge structure reveals that Mn ions take the valency of 2+, which is consistent with Mn-L2, 3 near edge x-ray absorption results in our previous report.
Enhanced charge-discharge characteristics of RuO2 supercapacitors on heat-treated TiO2 nanorods
Authors: Ahn Young Rack , Park Chong Rae , Jo Seong Mu , Kim Dong Young
Published: March 2007

Electrochemical capacitors based on RuO2 were prepared onto electrospun TiO2 nanorods. Further heat treatment of the TiO2 at 800°C under nitrogen was found to greatly improve the electrochemical performance of the RuO2 electrodes, especially at fast charge-discharge rates. The specific capacitance was found to decrease by only 33% when the scan rate increased from 10to1000mVs−1 (from 687to460Fg−1). The characteristic response time of the RuO2 electrode was found to be 0.15s when a heat-treated TiO2 substrate was used, which is 20 times better than that of the pristine TiO2 used.
High-efficiency deep blue host for organic light-emitting devices
Authors: Gao Zhi Qiang , Mi Bao Xiu , Chen Chin H. , Cheah Kow Wai , Cheng Yuen Kit , Wen Wen-Shih
Published: March 2007

High-efficiency deep blue organic light-emitting devices have been fabricated using asymmetrically substituted 9-(α-naphthyl)-10-(β-naphthyl)-anthracene as blue host material and diphenyl-[4-(2-[1,1′;4′,1″]terphenyl-4-yl-vinyl)-phenyl]amine as dopant emitter. With an optimized device structure and doping concentration, the deep blue electroluminescent (EL) device achieved an EL efficiency of 4.9cd∕A and an external quantum efficiency of 4.4% at a current density of 20mA∕cm2 at saturated blue Commission Internationale de l’Eclairage coordinates of (0.15, 0.13). The deep blue device also has a current efficiency which is invariable with driving conditions ranging from 10to100mA∕cm2.
Near field distribution in two dimensionally arrayed gold nanoparticles on platinum substrate
Authors: Nedyalkov Nikolay , Sakai Tetsuo , Miyanishi Tomoya , Obara Minoru
Published: March 2007

Theoretical and experimental results for near field properties in the vicinity of two dimensionally aligned gold nanoparticles are presented. The numerical analysis is based on finite difference time domain simulation code. The simulated system consists of gold particles with a radius of 100nm, deposited on platinum substrate. The near field distribution on the substrate surface and its magnitude are found to depend on the interparticle distance. The experimental results obtained confirm the theoretical findings and demonstrate that the produced near field can result in a permanent substrate surface nanomodification and selective nanoparticle removal.
Nonvolatile polycrystalline silicon thin-film-transistor memory with oxide/nitride/oxide stack gate dielectrics and nanowire channels
Authors: Chen Shih-Ching , Chang Ting-Chang , Liu Po-Tsun , Wu Yung-Chun , Yeh Ping-Hung , Weng Chi-Feng , Sze S. M. , Chang Chun-Yen , Lien Chen-Hsin
Published: March 2007

In this work, the authors study a polycrystalline silicon thin-film transistor (poly-Si TFT) with oxide/nitride/oxide (ONO) stack gate dielectrics and multiple nanowire channels for the applications of both nonvolatile silicon-oxide-nitride-oxide-silicon (SONOS) memory and switch transistor. The proposed device named as nanowire SONOS-TFT has superior electrical characteristics of a transistor such as on/off current ratio, threshold voltage (Vth), and subthreshold slope due to the good gate control ability originated from fringing electrical field effects. Moreover, the proposed device under adequate operation scheme can exhibit high program/erase efficiency and good retention time characteristics at high temperature.
On-chip electron-impact ion source using carbon nanotube field emitters
Authors: Bower Christopher A. , Gilchrist Kristin H. , Piascik Jeffrey R. , Stoner Brian R. , Natarajan Srividya , Parker Charles B. , Wolter Scott D. , Glass Jeffrey T.
Published: March 2007

A lateral on-chip electron-impact ion source utilizing a carbon nanotube field emission electron source was fabricated and characterized. The device consists of a cathode with aligned carbon nanotubes, a control grid, and an ion collector electrode. The electron-impact ionization of He, Ar, and Xe was studied as a function of field emission current and pressure. The ion current was linear with respect to gas pressure from 10−4to10−1Torr. The device can operate as a vacuum ion gauge with a sensitivity of approximately 1Torr−1. Ion currents in excess of 1μA were generated.
Hysteresis and threshold voltage shift of pentacene thin-film transistors and inverters with Al2O3 gate dielectric
Authors: Koo Jae Bon , Ku Chan Hoe , Lim Sang Chul , Kim Seong Hyun , Lee Jung Hun
Published: March 2007

The pentacene organic thin-film transistors (OTFTs) with plasma-enhanced atomic-layer-deposited 150nm thick Al2O3 as a gate dielectric and the inverters comprised of these OTFTs have been fabricated. The hysteresis in transfer characteristics of the OTFTs depends on the scan range of negative gate voltage, regardless of drain voltage. Negative gate-bias stress leads to the progressive negative shift of threshold voltage. The hysteresis of D inverter is similar to that of E inverter, but the former has a wider swing range and a higher gain in comparison with the latter.
Dependence of ion sheath collapse on secondary electron emission in plasma immersion ion implantation
Authors: Kwok Dixon T. K. , Pu Shihao , Fu Ricky K. Y. , Jin Fanya , Chu Paul K.
Published: March 2007

The collapse of the ion sheath in front of a dielectric substrate during argon plasma immersion ion implantation is investigated using a Langmuir probe. The probe signals during the buildup and collapse of the ion sheath are recorded from a lime glass substrate with a magnesium metal plate placed on top. The collapsing speed of the ion sheath is shown to strongly depend on the secondary electron emission coefficient of the substrate. The authors’ results show that it is possible to derive secondary electron emission coefficients from insulating materials based on the probe signals.
Thermodynamic Properties of the KCl+H2O System
Authors: Archer Donald G.
Published: March 2007

The thermodynamic properties of the KCl+H2O system were examined in order to provide: (1) an improved equation for the osmotic coefficient as a function of molality and temperature for purposes of isopiestic measurements, (2) a determination of the thermodynamic properties of the standard-state solution process, and (3) a test of the accuracy of the enthalpy of solution values for KCl(cr), a calorimetric standard. New equations that describe the thermodynamic properties of the KCl+H2O system were obtained from previously published measurements for this system. The measured values included in the fitted equations spanned the range of temperature from approximately 260 to 420 K for KCl(aq) and 1.5 K to 1033.7 K for KCl(cr). New equations and/or values for the following properties are given in the present work: (1) thermal properties of KCl(cr) from 0 K to the melting point, 1045 K, (2) the change in chemical potential for both KCl and H2O in KCl(aq) as a function of temperature, and molality, valid from 260 to 420 K, and (3) standard-state properties for the aqueous solution process. The effect of heat treatment on the determination of enthalpy of solution values was also examined. This examination indicated that the NIST recommendation of heating Standard Reference Material 1655, potassium chloride, at 800 K for a minimum of 4 h prior to its use in calorimeter calibration, should probably not be followed. The heat treatment recommended by the NIST certificate appears, at this point, to have a higher probability of corrupting the sample than improving the accuracy of the measurement.
The Unstable Public-Health Ecology of the New York Metropolitan Region: Implications for Accelerated National Spread of Emerging Infection
Authors: Wallace Rodrick , McCarthy Kristin
Published: March 2007

Empirical techniques adapted from ecosystem-resilience theory allow estimation of how public health and public order within the New York Metropolitan Region respond to perturbations driven by changes in policy or economic structure. This approach constitutes a rigorous methodology for health-impact assessment, providing a quantitative measure of the stability of the region. Contrary to entrenched cultural assumption, affluent suburban counties and impoverished central-city neighborhoods remain strongly linked through a probability-of-contact matrix well indexed by the daily journey to work. The public-health ecology of the New York Metropolitan Region is remarkably unstable, greatly amplifying perturbations through mechanisms analogous to positive feedback in mechanical systems, with the single greatest influence being the percentage of the population living in poverty. Given the New York region's overwhelming dominance of national patterns for the hierarchical diffusion of disease and disorder this result has significant policy implication. More explicitly, lowering the rate of poverty in and near New York City would markedly reduce the vulnerability of the United States to emerging infection.
Global Events, National Politics, Local Lives: Young Muslim Men in Scotland
Authors: Hopkins Peter
Published: March 2007

In this paper I explore the influence of global events on the lives and experiences of young Muslim men living in postdevolution urban Scotland. Expanding upon understandings of scale, I highlight the complex ways that scale is struggled for and over, and in doing so challenge the notion that young people are disengaged from, and apathetic about, mainstream politics. Drawing on the young men's reactions and experiences of the global, nation, state, and local scales following 11 September 2001 and the subsequent war in Iraq, in this paper I include the voices of minority ethnic youth in political geographies and understandings of political participation.
Two monitoring methods that assess species composition and spatio-temporal trends in bycatch from an important temperate rock lobster (Jasus edwardsii) fishery
Authors: Brock Daniel J. , Hawthorne Peter J. , Ward Timothy M. , Linnane Adrian J.
Published: March 2007

The effectiveness of two monitoring programs, designed to describe and quantify the bycatch from commercial pots, was examined in the South Australian rock lobster (Jasus edwardsii) fishery (SARLF). The first, logbook sampling, relied on information collected and recorded by fishers in logbooks. The second, bycatch sampling, required fishers to collect bycatch specimens on a nominated day for later scientific analysis. A total of 40 bycatch species were recorded during the study. Finfish, mainly blue-throat wrasse (Notolabrus tetricus) and leather jacket species (Meuschenia hippocrepis and Meushenia australis), were the major component (>90% by number). Data from the logbook program were appropriate for monitoring spatio-temporal trends in bycatch, whereas the bycatch sampling provided more accurate information on bycatch species. Each program was subject to bias when estimating total bycatch numbers and, as a result, a combination of both methods indicated a cost-effective and appropriate way with which to monitor bycatch from the fishery. In comparison with other fisheries, bycatch from the SARLF was relatively low; however, because bycatch was dominated by relatively few species, ongoing monitoring and risk assessment of these populations is needed to ensure long-term sustainability of bycatch levels.
Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer
Authors: Mehrian-Shai R. , Chen C. D. , Shi T. , Horvath S. , Nelson S. F. , Reichardt J. K. V. , Sawyers C. L.
Published: March 2007

PTEN is an important tumor-suppressor gene associated with many cancers. Through expression profiling of glioblastoma tissue samples and prostate cancer xenografts, we identified a molecular signature for loss of the PTEN tumor suppressor in glioblastoma and prostate tumors. The PTEN signature consists of a minimum of nine genes, several of which are involved in various pathways already implicated in tumor formation. Among these signature genes, the most significant was an increase in insulin growth factor-binding protein 2 (IGFBP-2) mRNA. Up-regulation of IGFBP-2 was confirmed at the protein level by Western blot analysis and validated in samples not included in the microarray analysis. The link between IGFBP-2 and PTEN was of particular interest because elevated serum IGFBP-2 levels have been reported in patients with prostate and brain tumors. To further investigate this link, we determined that IGFBP-2 expression is negatively regulated by PTEN and positively regulated by phosphatidylinositol 3-kinase (PI3K) and Akt activation. In addition, Akt-driven transformation is impaired in IGFBP2
−/−
mouse embryo fibroblasts, implicating a functional role for IGFBP-2 in PTEN signaling. Collectively, these studies establish that PTEN and IGFBP-2 expression are inversely correlated in human brain and prostate cancers and implicate serum IGFBP-2 levels as a potential serum biomarker of PTEN status and PI3K Akt pathway activation in cancer patients.
Genome and proteome of long-chain alkane degrading
Geobacillus thermodenitrificans
NG80-2 isolated from a deep-subsurface oil reservoir
Authors: Feng Lu , Wang Wei , Cheng Jiansong , Ren Yi , Zhao Guang , Gao Chunxu , Tang Yun , Liu Xueqian , Han Weiqing , Peng Xia , Liu Rulin , Wang Lei
Published: March 2007

The complete genome sequence of
Geobacillus thermodenitrificans
NG80-2, a thermophilic bacillus isolated from a deep oil reservoir in Northern China, consists of a 3,550,319-bp chromosome and a 57,693-bp plasmid. The genome reveals that NG80-2 is well equipped for adaptation into a wide variety of environmental niches, including oil reservoirs, by possessing genes for utilization of a broad range of energy sources, genes encoding various transporters for efficient nutrient uptake and detoxification, and genes for a flexible respiration system including an aerobic branch comprising five terminal oxidases and an anaerobic branch comprising a complete denitrification pathway for quick response to dissolved oxygen fluctuation. The identification of a nitrous oxide reductase gene has not been previously described in Gram-positive bacteria. The proteome further reveals the presence of a long-chain alkane degradation pathway; and the function of the key enzyme in the pathway, the long-chain alkane monooxygenase LadA, is confirmed by
in vivo
and
in vitro
experiments. The thermophilic soluble monomeric LadA is an ideal candidate for treatment of environmental oil pollutions and biosynthesis of complex molecules.
Assess the nature of cholesterol–lipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers
Authors: Ali Md Rejwan , Cheng Kwan Hon , Huang Juyang
Published: March 2007

Cholesterol plays a vital role in determining the physiochemical properties of cell membranes. However, the detailed nature of cholesterol–lipid interactions is a subject of ongoing debate. Existing conceptual models, including the Condensed Complex Model, the Superlattice Model, and the Umbrella Model, identify different molecular mechanisms as the key to cholesterol–lipid interactions. In this work, the compositional dependence of the chemical potential of cholesterol in cholesterol/phosphatidylcholine mixtures was systematically measured at high resolution at 37°C by using an improved cholesterol oxidase (COD) activity assay. The chemical potential of cholesterol was found to be much higher in di18:1-PC bilayers than in di16:0-PC bilayers, indicating a more favorable interaction between cholesterol and saturated chains. More significantly, in 16:0,18:1-PC and di18:1-PC bilayers, the COD initial-reaction rate displays a series of distinct jumps near the cholesterol mole fractions (χ
C
) of 0.15, 0.25, 0.40, 0.50, and 0.57 and a peak at the cholesterol maximum solubility limit of 0.67. These jumps have been identified as the thermodynamic signatures of stable cholesterol regular distributions. In contrast, no such jumps were evident in di16:0-PC bilayers below χ
C
of 0.57. The observed chemical potential profile is in excellent agreement with previous Monte Carlo simulations based on the Umbrella Model but not with the predictions from the other models. The data further indicate that the cholesterol regular distribution domains (superlattices) are not the hypothesized condensed complexes. Those complexes were mainly implicated from studies on lipid monolayer that may not be relevant to the lipid bilayer in cell membranes.
Proteorhodopsin photosystem gene expression enables photophosphorylation in a heterologous host
Authors: Martinez A. , Bradley A. S. , Waldbauer J. R. , Summons R. E. , DeLong E. F.
Published: March 2007

Proteorhodopsins (PRs) are retinal-containing proteins that catalyze light-activated proton efflux across the cell membrane. These photoproteins are known to be globally distributed in the ocean's photic zone, and they are found in a diverse array of Bacteria and Archaea. Recently, light-enhanced growth rates and yields have been reported in at least one PR-containing marine bacterium, but the physiological basis of light-activated growth stimulation has not yet been determined. To describe more fully PR photosystem genetics and biochemistry, we functionally surveyed a marine picoplankton large-insert genomic library for recombinant clones expressing PR photosystems
in vivo
. Our screening approach exploited transient increases in vector copy number that significantly enhanced the sensitivity of phenotypic detection. Two genetically distinct recombinants, initially identified by their orange pigmentation, expressed a small cluster of genes encoding a complete PR-based photosystem. Genetic and biochemical analyses of transposon mutants verified the function of gene products in the photopigment and opsin biosynthetic pathways. Heterologous expression of six genes, five encoding photopigment biosynthetic proteins and one encoding a PR, generated a fully functional PR photosystem that enabled photophosphorylation in recombinant
Escherichia coli
cells exposed to light. Our results demonstrate that a single genetic event can result in the acquisition of phototrophic capabilities in an otherwise chemoorganotrophic microorganism, and they explain in part the ubiquity of PR photosystems among diverse microbial taxa.
Earliest evidence of modern human life history in North African early
Homo sapiens
Authors: Smith Tanya M. , Tafforeau Paul , Reid Donald J. , Grün Rainer , Eggins Stephen , Boutakiout Mohamed , Hublin Jean-Jacques
Published: March 2007

Recent developmental studies demonstrate that early fossil hominins possessed shorter growth periods than living humans, implying disparate life histories. Analyses of incremental features in teeth provide an accurate means of assessing the age at death of developing dentitions, facilitating direct comparisons with fossil and modern humans. It is currently unknown when and where the prolonged modern human developmental condition originated. Here, an application of x-ray synchrotron microtomography reveals that an early
Homo sapiens
juvenile from Morocco dated at 160,000 years before present displays an equivalent degree of tooth development to modern European children at the same age. Crown formation times in the juvenile's macrodont dentition are higher than modern human mean values, whereas root development is accelerated relative to modern humans but is less than living apes and some fossil hominins. The juvenile from Jebel Irhoud is currently the oldest-known member of
Homo
with a developmental pattern (degree of eruption, developmental stage, and crown formation time) that is more similar to modern
H. sapiens
than to earlier members of
Homo
. This study also underscores the continuing importance of North Africa for understanding the origins of human anatomical and behavioral modernity. Corresponding biological and cultural changes may have appeared relatively late in the course of human evolution.
p53 targets identified by protein expression profiling
Authors: Rahman-Roblick Rubaiyat , Johannes Roblick Uwe , Hellman Ulf , Conrotto Paolo , Liu Tao , Becker Susanne , Hirschberg Daniel , Jörnvall Hans , Auer Gert , Wiman Klas G.
Published: March 2007

p53 triggers cell cycle arrest and apoptosis through transcriptional regulation of specific target genes. We have investigated the effect of p53 activation on the proteome using 2D gel electrophoresis analysis of mitomycin C-treated HCT116 colon carcinoma cells carrying wild-type p53. Approximately 5,800 protein spots were separated in overlapping narrow-pH-range gel strips, and 115 protein spots showed significant expression changes upon p53 activation. The identity of 55 protein spots was obtained by mass spectrometry. The majority of the identified proteins have no previous connection to p53. The proteins fall into different functional categories, such as mRNA processing, translation, redox regulation, and apoptosis, consistent with the idea that p53 regulates multiple cellular pathways. p53-dependent regulation of five of the up-regulated proteins, eIF5A, hnRNP C1/C2, hnRNP K, lamin A/C, and Nm23-H1, and two of the down-regulated proteins, Prx II and TrpRS, was examined in further detail. Analysis of mRNA expression levels demonstrated both transcription-dependent and transcription-independent regulation among the identified targets. Thus, this study reveals protein targets of p53 and highlights the role of transcription-independent effects for the p53-induced biological response.
A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis
Authors: Singh Amrik J. , Meyer Rosana D. , Navruzbekov Gyulmagomed , Shelke Rajani , Duan Lei , Band Hamid , Leeman Susan E. , Rahimi Nader
Published: March 2007

Activation of phospholipase Cγ1 (PLCγ1) by vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells in part is responsible for angiogenesisin vivo. The cellular mechanisms exerting negative control over PLCγ1 activation, however, remain unaddressed. Here by usingin vitroandin vivobinding assays, we show that the Casitas B-lineage lymphoma (c-Cbl) E3 ubiquitin ligase constitutively associates with PLCγ1 via its C-terminal domain and conditionally interacts with VEGFR-2 via the N-terminal/TKB domain. Site-directed mutagenesis of VEGFR-2 showed that full activation of c-Cbl requires its direct association with phospho-tyrosines 1052 and 1057 of VEGFR-2 via its TKB domain and indirect association with phospho-tyrosine 1173 of VEGFR-2 via PLCγ1. The tertiary complex formation between VEGFR-2, PLCγ1 and c-Cbl selectively promotes ubiquitylation and suppression of tyrosine phosphorylation of PLCγ1 by a proteolysis-independent mechanism. Further analysis showed that association of c-Cbl with VEGFR-2 does not impact ubiquitylation, down-regulation, or tyrosine phosphorylation of VEGFR-2. Silencing of c-Cbl by siRNA revealed that endogenous c-Cbl plays an inhibitory role in angiogenesis. Our data demonstrate that corecruitment of c-Cbl and PLCγ1 to VEGFR-2 serves as a mechanism to fine-tune the angiogenic signal relay of VEGFR-2.
Learning-related coordination of striatal and hippocampal theta rhythms during acquisition of a procedural maze task
Authors: DeCoteau William E. , Thorn Catherine , Gibson Daniel J. , Courtemanche Richard , Mitra Partha , Kubota Yasuo , Graybiel Ann M.
Published: March 2007

The striatum and hippocampus are conventionally viewed as complementary learning and memory systems, with the hippocampus specialized for fact-based episodic memory and the striatum for procedural learning and memory. Here we directly tested whether these two systems exhibit independent or coordinated activity patterns during procedural learning. We trained rats on a conditional T-maze task requiring navigational and cue-based associative learning. We recorded local field potential (LFP) activity with tetrodes chronically implanted in the caudoputamen and the CA1 field of the dorsal hippocampus during 6–25 days of training. We show that simultaneously recorded striatal and hippocampal theta rhythms are modulated differently as the rats learned to perform the T-maze task but nevertheless become highly coherent during the choice period of the maze runs in rats that successfully learned the task. Moreover, in the rats that acquired the task, the phase of the striatal–hippocampal theta coherence was modified toward a consistent antiphase relationship, and these changes occurred in proportion to the levels of learning achieved. We suggest that rhythmic oscillations, including theta-band activity, could influence not only neural processing in cortico-basal ganglia circuits but also dynamic interactions between basal ganglia-based and hippocampus-based forebrain circuits during the acquisition and performance of learned behaviors. Experience-dependent changes in coordination of oscillatory activity across brain structures thus may parallel the well known plasticity of spike activity that occurs as a function of experience.
Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages
Authors: Meinen Sarina , Barzaghi Patrizia , Lin Shuo , Lochmüller Hanns , Ruegg Markus A.
Published: March 2007

Mutations in laminin-α2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-α2 are dystroglycan and α7β1 integrin. We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-agrin), which binds to dystroglycan but not to α7β1 integrin, substantially ameliorates the disease (Moll, J., P. Barzaghi, S. Lin, G. Bezakova, H. Lochmuller, E. Engvall, U. Muller, and M.A. Ruegg. 2001. Nature. 413:302–307; Bentzinger, C.F., P. Barzaghi, S. Lin, and M.A. Ruegg. 2005. Matrix Biol. 24:326–332.). Now we show that late-onset expression of mini-agrin still prolongs life span and improves overall health, although not to the same extent as early expression. Furthermore, a chimeric protein containing the dystroglycan-binding domain of perlecan has the same activities as mini-agrin in ameliorating the disease. Finally, expression of full-length agrin also slows down the disease. These experiments are conceptual proof that linking the basement membrane to dystroglycan by specifically designed molecules or by endogenous ligands, could be a means to counteract MDC1A at a progressed stage of the disease, and thus opens new possibilities for the development of treatment options for this muscular dystrophy.
Ignition and combustion of low-exothermicity porous materials by a local hotspot
Authors: Shah A.A , Brindley J , McIntosh A.C , Griffiths J
Published: March 2007

We present numerical investigations of a spherically symmetric model for the ignition and subsequent combustion of low-exothermicity porous materials exposed to a constant, continuous heat source. We account simultaneously for oxidant, the gas-dynamic processes, including a gaseous product of reaction, and a solid product that is allowed to assume different physical properties from the solid reactant. For external conditions that are typical of natural convection, the model exhibits striking novel behaviour, including the possibility of a potentially dangerous high-temperature ‘burnout’ at the external surface of the material, which triggers a reverse combustion wave propagating from the outer surface of the solid towards the heat source. This phenomenology is controlled largely by the diffusion of oxygen entering the system. We identify the effects that convection and product properties have on combustion of the solid, particularly on the formation of a reverse wave. Applications of the approach to specific problems are discussed and future work is outlined.
Contribution of H7 haemagglutinin to amantadine resistance and infectivity of influenza virus
Authors: Ilyushina Natalia A. , Govorkova Elena A. , Russell Charles J. , Hoffmann Erich , Webster Robert G.
Published: March 2007

In the present study we determined the antiviral effect of amantadine against influenza A/Netherlands/219/03 (H7N7) virus in cell culture and in a mouse model. Amantadine at concentrations <100 μM failed to inhibit virus replication in Madin–Darby canine kidney (MDCK) cells. When orally administered to mice for 5 days, amantadine at 15 mg kg−1 day−1 did not protect animals against lethal challenge with H7N7 infection, and virus titres in mouse organs were not reduced. However, sequence analysis of the M2 protein revealed none of the mutations previously described as being associated with amantadine resistance. We used reverse genetics to generate viruses containing the haemagglutinin (HA) or M gene of A/Netherlands/219/03 virus to investigate the role of these genes in amantadine sensitivity. All recombinant viruses carrying the HA segment of A/Netherlands/219/03 (H7N7) virus were amantadine-resistant, regardless of the origin of their other genes. To study the role of fusion activity in the mechanism of drug resistance, we introduced the Gly23→Cys mutation in the H7 fusion peptide. This substitution resulted in a decrease of the pH of fusion and was also associated with reduced virus replication in both MDCK cells and mice, as compared to that of the wild-type virus. We suggest that H7 HA protein plays a role in amantadine resistance, although all HA amino acids that participate in drug resistance still remain to be characterized. Our finding reveals that sequence analysis of the transmembrane domain of M2 protein may not adequately identify all drug-resistant variants.
Genetic variability of the M genome segment of clinical and environmental Toscana virus strains
Authors: Venturi Giulietta , Ciccozzi Massimo , Montieri Stefania , Bartoloni Alessandro , Francisci Daniela , Nicoletti Loredana , Fortuna Claudia , Marongiu Luigi , Rezza Giovanni , Ciufolini Maria Grazia
Published: March 2007

Twenty-seven strains of Toscana virus, collected over a period of 23 years and isolated from several localities and from different hosts (humans, arthropods and a bat), were investigated by sequencing of a portion of the M genomic segment comprising the GNglycoprotein coding region. Sequence data indicated that the divergence among isolates ranged from 0 to 5.7 % at the nucleotide level and from 0 to 3.4 % at the amino acid level. Phylogenetic analysis revealed four main clusters. A close correspondence between viral strains and area/year of isolation could not be demonstrated, whilst co-circulation of different viral strains in the same area and in the same time period was observed for both patients and environmental viral isolates. Alignment of the deduced amino acid sequences and evolutionary analysis indicated that most of the sites along the gene may be invariable because of purifying and/or neutral selection.
Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus
Authors: Tagmyer Tara L. , Craigo Jodi K. , Cook Sheila J. , Issel Charles J. , Montelaro Ronald C.
Published: March 2007

Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whilst the antibody-neutralization determinants of Env have been defined, there are to date no comprehensive analyses of the lymphoproliferative (T-helper, Th) and cytotoxic T-cell (CTL) epitopes of the EIAV Env proteins. Thus, in the current study, synthetic-peptide methodologies were used to define regions of EIAV Env associated with protective vaccine immunity in a panel of 12 horses inoculated with the attenuated EIAVD9 vaccine and two asymptomatic carrier horses infected experimentally with the virulent EIAVPV strain expressing the same Env protein as the vaccine strain. The results of these studies identified 17 broadly reactive Th peptides and six broadly reactive CTL peptides in the Env proteins of EIAV that were associated with protective immunity. Thus, these data provide for the first time a comprehensive mapping of EIAV Env-specific cellular regions that can be used to examine the development of protective immunity and to evaluate potential cellular immune determinants of protective immunity.
Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle
Authors: Wells G. A. H. , Konold T. , Arnold M. E. , Austin A. R. , Hawkins S. A. C. , Stack M. , Simmons M. M. , Lee Y. H. , Gavier-Widén D. , Dawson M. , Wilesmith J. W.
Published: March 2007

The dose–response of cattle exposed to the bovine spongiform encephalopathy (BSE) agent is an important component of modelling exposure risks for animals and humans and thereby, the modulation of surveillance and control strategies for BSE. In two experiments calves were dosed orally with a range of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in the pool was determined by end-point titration in mice. Recipient cattle were monitored for clinical disease and, from the incidence of pathologically confirmed cases and their incubation periods (IPs), the attack rate and IP distribution according to dose were estimated. The dose at which 50 % of cattle would be clinically affected was estimated at 0.20 g brain material used in the experiment, with 95 % confidence intervals of 0.04–1.00 g. The IP was highly variable across all dose groups and followed a log-normal distribution, with decreasing mean as dose increased. There was no evidence of a threshold dose at which the probability of infection became vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1 mg).
Soluble 3-O-sulfated heparan sulfate can trigger herpes simplex virus type 1 entry into resistant Chinese hamster ovary (CHO-K1) cells
Authors: Tiwari Vaibhav , O'Donnell Christopher , Copeland Ronald J. , Scarlett Tanya , Liu Jian , Shukla Deepak
Published: March 2007

Herpes simplex virus type 1 (HSV-1) interaction with glycoprotein D (gD) receptors facilitates virus entry into cells. Chinese hamster ovary (CHO-K1) cells lacking cellular receptors allow virus to attach, but not to enter, implying a role for receptors during the post-attachment (entry) phase of HSV-1 infection. Here, it is shown that the presence of soluble heparan sulfate (HS) modified by 3-O-sulfotransferase-3 (3-OST-3), but not by 3-OST-1, triggered HSV-1 entry into resistant CHO-K1 cells. It was further demonstrated that a CHO-K1 mutant deficient in glycosaminoglycan synthesis became susceptible to entry when spinoculated in the presence of 3-OST-3-modified soluble HS, indicating that the role of the gD receptor is to trigger entry rather than cell attachment. In separate experiments, 3-OST-3-modified soluble HS also triggered fusion of HSV-1 glycoprotein-expressing cells with CHO-K1 cells. Taken together, these results show that association of gD with cell surface-bound receptor is not essential for HSV-1 entry and spread.
Human MxA protein confers resistance to double-stranded RNA viruses of two virus families
Authors: Mundt Egbert
Published: March 2007

The interferon-induced human MxA protein belongs to the dynamin superfamily of large GTPases and accumulates in the cytoplasm. MxA is a key component of the innate antiviral response and has previously been shown to inhibit several viruses with single-stranded RNA genomes of both polarities and a DNA virus. In addition, MxA also targets two double-stranded RNA viruses, Infectious bursal disease virus and a mammalian reovirus as shown in this study. Thus, the antiviral spectrum of human MxA is broader than hitherto suspected. Interestingly, virus growth was not affected in cells expressing MxA(E645R), a mutant form of MxA that showed antiviral activity against orthomyxoviruses.
Comparative full-length sequence analysis of oncogenic and vaccine (Rispens) strains of Marek's disease virus
Authors: Spatz Stephen J. , Petherbridge Lawrence , Zhao Yuguang , Nair Venugopal
Published: March 2007

The complete DNA sequence of the Marek's disease virus serotype 1 vaccine strain CVI988 was determined and consists of 178 311 bp with an overall gene organization identical to that of the oncogenic strains. In examining open reading frames (ORFs), nine differ between vaccine and oncogenic strains. A 177 bp insertion was identified in the overlapping genes encoding the Meq, RLORF6 and 23 kDa proteins of CVI988. Three ORFs are predicted to encode truncated proteins. One, designated 49.1, overlaps the gene encoding the large tegument protein UL36 and encodes a severely truncated protein of 34 aa. The others, ORF5.5/ORF75.91 and ORF3.0/78.0, located in the repeat regions (diploid), encode a previously unidentified ORF of 52 aa and a truncated version of the virus-encoded chemokine (vIL-8), respectively. Subtle genetic changes were identified in the two ORFs encoding tegument proteins UL36 and UL49. Only one diploid ORF (ORF6.2/ORF75.6) present in the genomes of the three virulent strains is absent in the CVI988-BAC genome. Seventy non-synonymous amino acid substitutions were identified that could differentiate CVI988-BAC from all three oncogenic strains collectively. Estimates of the non-synonymous to synonymous substitution ratio (ω) indicate that CVI988 ORFs are generally under purifying selection (ω<1), whereas UL39, UL49, UL50, RLORF6 and RLORF7 (Meq) appear to evolve under relaxed selective constraints. No CVI988 ORF was found to be under positive evolutionary selection (ω≫1).
Sequence and organization of the Heliothis virescens ascovirus genome
Authors: Asgari Sassan , Davis John , Wood David , Wilson Peter , McGrath Annette
Published: March 2007

The nucleotide sequence of the Heliothis virescens ascovirus (HvAV-3e) DNA genome was determined and characterized in this study. The circular genome consists of 186 262 bp, has a G+C content of 45.8 mol% and encodes 180 potential open reading frames (ORFs). Five unique homologous regions (hrs), 23 ‘baculovirus repeat ORFs' (bro) and genes encoding a caspase homologue and several enzymes involved in nucleotide replication and metabolism were found in the genome. Several ascovirus (AV)-, iridovirus- and baculovirus-homologous genes were identified. The genome is significantly larger than the recently sequenced genomes of Trichoplusia ni AV (TnAV-2c) and Spodoptera frugiperda AV (SfAV-1a). Gene-parity plots and overall similarity of ORFs indicate that HvAV-3e is related more closely to SfAV-1a than to TnAV-2c.
In vivo evidence for quasispecies distributions in the bovine respiratory syncytial virus genome
Authors: Deplanche Martine , Lemaire Mylène , Mirandette Carole , Bonnet Marion , Schelcher François , Meyer Gilles
Published: March 2007

We analysed the genetic evolution of bovine respiratory syncytial virus (BRSV) isolate W2-00131, from its isolation in bovine turbinate (BT) cells to its inoculation in calves. Results showed that the BRSV genomic region encoding the highly variable glycoprotein G remained genetically stable after virus isolation and over 10 serial infections in BT cells, as well as following experimental inoculation in calves. This remarkable genetic stability led us to examine the mutant spectrum of several populations derived from this field isolate. Sequence analysis of molecular clones revealed an important genetic heterogeneity in the G-coding region of each population, with mutation frequencies ranging from 6.8 to 10.1×10−4substitutions per nucleotide. The non-synonymous mutations of the mutant spectrum mapped preferentially within the two variable antigenic regions of the ectodomain or close to the highly conserved domain. These results suggest that BRSV populations may evolve as complex and dynamic mutant swarms, despite apparent genetic stability.
Impact of a basement membrane-degrading protease on dissemination and secondary infection of Autographa californica multiple nucleopolyhedrovirus in Heliothis virescens (Fabricus)
Authors: Li Huarong , Tang Hailin , Harrison Robert L. , Bonning Bryony C.
Published: March 2007

ScathL is a cathepsin L-like cysteine protease from the flesh fly,Sarcophaga peregrina, that digests components of the basement membrane (BM) during insect metamorphosis. A recombinant baculovirus that expresses ScathL (AcMLF9.ScathL) kills larvae of the tobacco budworm,Heliothis virescens, significantly faster than the wild-type virus and triggers melanization and tissue fragmentation in infected larvae shortly before death. As BMs are a potential barrier to the spread of baculovirus secondary infection to other tissues in the host, this study tested the hypothesis that the rapid death of insects infected with AcMLF9.ScathL was caused by accelerated secondary infection resulting from the degradation of host BMs by ScathL. Viruses expressing catalytically active or inactive ScathL were used to examine the effects of ScathL activity on budded virus release into the haemocoel during infection, the production of polyhedra in infected larvae and the rate of infection of the gut, trachea, haemocytes, fat body and Malpighian tubules. It was concluded that the enhanced insecticidal efficacy of the recombinant baculovirus that expresses ScathL does not result from altered tissue tropism or accelerated systemic infection. Implications for the role of the BM as a barrier to baculovirus dissemination within the host insect are discussed.
Transcriptional reactivation of murine cytomegalovirus ie gene expression by 5-aza-2′-deoxycytidine and trichostatin A in latently infected cells despite lack of methylation of the major immediate-early promoter
Authors: Hummel Mary , Yan Shixian , Li Zhigao , Varghese Thomas K. , Abecassis Michael
Published: March 2007

We have used a spleen explant model to investigate mechanisms of murine cytomegalovirus latency and reactivation. Induction of immediate-early (ie) gene expression occurs in explants after approximately 9 days in culture and virus reactivation follows induction of ie gene expression with kinetics similar to that of productive infection in vitro. This occurs independently of TNF receptor signalling. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor trichostatin A results in more rapid induction of ie gene expression and reactivation of virus. Despite these results, which suggest a role for DNA methylation in maintenance of viral latency, we find that the major immediate-early promoter/enhancer is not methylated in latently infected mice. Our results support the hypothesis that latency is maintained by epigenetic control of ie gene expression, and that induction of ie gene expression leads to reactivation of virus, but suggest that these are not controlled by DNA methylation.
A novel, multipartite, negative-strand RNA virus is associated with the ringspot disease of European mountain ash (Sorbus aucuparia L.)
Authors: Mielke Nicole , Muehlbach Hans-Peter
Published: March 2007

Four RNAs from a new plant-pathogenic virus, which we have tentatively named European mountain ash ringspot-associated virus (EMARAV), were identified and sequenced completely. All four viral RNAs could be detected in previous double-stranded RNA preparations. RNA 1 (7040 nt) encodes a protein with similarity to the RNA-dependent RNA polymerase of different members of the Bunyaviridae, a family containing five genera with viruses infecting invertebrates, vertebrates and plants. RNA 2 (2335 nt) encodes a 75 kDa protein containing a conserved motif of the glycoprotein precursor of the genus Phlebovirus. Immunological detection indicated the presence of proteins with the expected size of the precursor and one of its processing products. The amino acid sequence of protein p3 (35 kDa) encoded by RNA 3 shows similarities to a putative nucleocapsid protein of two still unclassified plant viruses. The fourth viral RNA encodes a 27 kDa protein that has no significant homology to any known protein. As is typical for members of the family Bunyaviridae, the 5′ and 3′ ends of all viral RNAs are complementary, which allows the RNA to form a panhandle structure. Comparison of these sequences demonstrates a conserved terminal part of 13 nt, similar to that of the bunyaviral genus Orthobunyavirus. Despite the high agreement of the EMARAV genome with several characteristics of the family Bunyaviridae, there are a few features that make it difficult to allocate the virus to this group. It is therefore more likely that this plant pathogen belongs to a novel virus genus.
Inferring planar disorder in close-packed structures via ∊-machine spectral reconstruction theory: structure and intrinsic computation in zinc sulfide
Authors: Varn D. P. , Canright G. S. , Crutchfield J. P.
Published: March 2007

We apply ∊-machine spectral reconstruction theory to analyze structure and disorder in four previously published zinc sulfide diffraction spectra and contrast the results with the most common alternative theory, the fault model. In each case we find that the reconstructed ∊-machine provides a more comprehensive and detailed understanding of the stacking structure, often detecting stacking structures not previously found. Using the ∊-machines reconstructed for each spectrum, we calculate a number of physical parameters – such as configurational energies, configurational entropies and hexagonality – and several quantities – including statistical complexity and excess entropy – that describe the intrinsic computational properties of the stacking structures.