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  • 1
  • 2
    Publication Date: 2013-10-10
    Print ISSN: 0024-9297
    Electronic ISSN: 1520-5835
    Topics: Chemistry and Pharmacology , Physics
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  • 3
    Publication Date: 2013-09-25
    Description: microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1) G93A rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1 G93A mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2012-02-14
    Description: Hot temperatures in combination with high humidity cause human discomfort and may increase morbidity and mortality. A global climate model with an embedded urban model is used to explore the urban-rural contrast in the wet-bulb globe temperature, a heat stress index accounting for temperature and humidity. Wet-bulb globe temperatures are calculated at each model time step to resolve the heat stress diurnal cycle. The model simulates substantially higher heat stress in urban areas compared to neighbouring rural areas. Urban humidity deficit only weakly offsets the enhanced heat stress due to the large night-time urban heat island. The urban-rural contrast in heat stress is most pronounced at night and over mid-latitudes and subtropics. During heatwaves, the urban heat stress amplification is particularly pronounced. Heat stress strongly increases with doubled CO2 concentrations over both urban and rural surfaces. The tropics experience the greatest increase in number of high-heat-stress nights, despite a relatively weak ∼2°C warming. Given the lack of a distinct annual cycle and high relative humidity, the modest tropical warming leads to exceedance of the present-day record levels during more than half of the year in tropical regions, where adaptive capacity is often low. While the absolute urban and rural heat stress response to 2 × CO2 is similar, the occurrence of nights with extremely high heat stress increases more in cities than surrounding rural areas.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 5
    Publication Date: 2011-04-13
    Description: Nucleolar stress, characterized by loss of nucleolar integrity, has not been described in the cardiac context. In addition to ribosome biogenesis, nucleoli are critical for control of cell proliferation and stress responses. Our group previously demonstrated induction of the nucleolar protein nucleostemin (NS) in response to cardiac pathological insult. NS interacts with nucleophosmin (NPM), a marker of nucleolar stress with cytoprotective properties. The dynamic behavior of NS and NPM reveal that nucleolar disruption is an early event associated with stress response in cardiac cells. Rapid translocation of NS and NPM to the nucleoplasm and suppression of new preribosomal RNA synthesis occurs in both neonatal rat cardiomyocytes (NRCM) and cardiac progenitor cells (CPC) upon exposure to doxorubicin or actinomycin D. Silencing of NS significantly increases cell death resulting from doxorubicin treatment in CPC, whereas NPM knockdown alone induces cell death. Overexpression of either NS or NPM significantly decreases caspase 8 activity in cultured cardiomyocytes challenged with doxorubicin. The presence of altered nucleolar structures resulting from myocardial infarction in mice supports the model of nucleolar stress as a general response to pathological injury. Collectively, these findings serve as the initial description of myocardial nucleolar stress and establish the postulate that nucleoli acts as sensors of stress, regulating the cellular response to pathological insults.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2013-12-07
    Description: Author(s): T. Fischer, K. Langanke, and G. Martínez-Pinedo We study the impact of neutrino-pair production from the de-excitation of highly excited heavy nuclei on core-collapse supernova simulations, following the evolution up to several 100 ms after core bounce. Our study is based on the agile-boltztran supernova code, which features general relativistic r... [Phys. Rev. C 88, 065804] Published Fri Dec 06, 2013
    Keywords: Nuclear Astrophysics
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
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  • 7
    Publication Date: 2013-10-09
    Description: The Costa Rica–Nicaragua subduction zone shows systematic along strike variation in arc chemistry, geology, tectonics and seismic velocity and attenuation, presenting global extremes within a few hundred kilometres. In this study, we use teleseismic and ambient noise derived surface wave tomography to produce a 3-D shear velocity model of the region. We use the 48 stations of the TUCAN array, and up to 94 events for the teleseismic Rayleigh wave inversion, and 18 months of continuous data for cross correlation to estimate Green's functions from ambient noise. In the shallow crust (0–15 km) we observe low-shear velocities directly beneath the arc volcanoes (〈3 km s –1 ) and higher velocities in the backarc of Nicaragua. The anomalies below the volcanoes are likely caused by heated crust, intruded by magma. We estimate crustal thickness by picking the depth to the 4 km s –1 velocity contour. We infer 〉40-km-thick crust beneath the Costa Rican arc and the Nicaraguan Highlands, thinned crust (~20 km) beneath the Nicaraguan Depression, and increasing crustal thickness in the backarc region, consistent with receiver function studies. The region of thinned, seismically slow and likely weakened crust beneath the arc in Nicaragua is not localizing deformation associated with oblique subduction. At mantle depths (55–120 km depth) we observe lower shear velocities (up to 3 per cent) beneath the Nicaraguan arc and backarc than beneath Costa Rica. Our low-shear velocity anomaly beneath Nicaragua is in the same location as a low-shear velocity anomaly and displaced towards the backarc from the high V P / V S anomaly observed in body wave tomography. The lower shear velocity beneath Nicaragua may indicate higher melt content in the mantle perhaps due to higher volatile flux from the slab or higher temperature. Finally, we observe a linear high-velocity region at depths 〉120 km parallel to the trench, which is consistent with the subducting slab.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 8
    Publication Date: 2011-09-17
    Description: We report on springtime 2010 observations of aerosol optical properties and size-resolved elemental composition from Mount Bachelor Observatory (MBO; 2763 meters above sea level). Observations included multiwavelength aerosol scattering and absorption, made with a nephelometer and a particle soot absorption photometer, and size-resolved composition, made using a rotating DRUM impactor with substrates analyzed by synchrotron X-ray fluorescence. Our main tool for investigating variability in composition was empirical orthogonal function (EOF) analysis. In April, dust and sulfate explained 96% of the variance in the observed fine composition and accounted for the majority of the fine mode scattering. Three coincident Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation overpasses also identified aerosol layers classified as dust or polluted dust over MBO. Later in the spring, we deduce that organics and nitrate comprised more than 50% of the submicrometer aerosol mass. We used the EOF analysis to identify systematic relationships between composition and optical properties. We observed dust accompanied by anthropogenic pollutants including sulfate. When present, dust aerosol controlled ∼30% of the variability in the wavelength dependence of fine mode scattering. Many of the samples containing sulfate had absorption Ångstrom exponents near 1, suggesting black carbon was also present. Most of the sulfate was in the fine mode, but sulfate was also observed on coarse aerosols, and we inferred that much of the coarse sulfur was coated on the dust or had formed CaSO4 during transport. The relationships between Fe, Ca, Al, and Si observed at MBO were consistent with previous observations of Asian dust transported to North America.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 9
    Publication Date: 2014-03-15
    Description: Seismic images of the base of the lithosphere across the San Andreas fault system (California, USA) yield new constraints on the distribution of deformation in the deep lithosphere beneath this strike-slip plate boundary. We show that conversions of shear to compressional waves (Sp) across the base of the lithosphere are systematically weaker on the western side of the plate boundary, indicating that the drop in seismic shear-wave velocity from lithosphere to asthenosphere is either smaller or occurs over a larger depth range. In central and northern California, the lithosphere-asthenosphere boundary changes character across a distance of 〈50 km, and does so directly beneath the San Andreas fault along its simple central segment, and beneath the Calaveras–Green Valley–Bartlett Springs faults to the north. Given the absolute velocities of the North America and Pacific plates, and low viscosities inferred for the asthenosphere, these results indicate the juxtaposition of mantle lithospheres with different properties across these faults. The spatial correlation between the central San Andreas fault and the laterally abrupt change in the velocity structure of the deepest mantle lithosphere points to the accommodation of relative plate motion on a narrow shear zone (〈50 km in width), and a rheology that enables strain localization throughout the thickness of the lithosphere.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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  • 10
    Publication Date: 2014-04-16
    Description: Observed seismic anisotropy and geochemical anomalies indicate the presence of 3-D flow around and above subducting slabs. To investigate how slab geometry and velocity affect mantle flow, we conducted a set of experiments using a subduction apparatus in a fluid-filled tank. Our models comprise two independently adjustable, continuous belts to represent discrete sections of subducting slabs that kinematically drive flow in the surrounding glucose syrup that represents the upper mantle. We analyse how slab dip (ranging from 30° to 80°), slab dip difference between slab segments (ranging from 20° to 50°), rates of subduction (4–8 cm yr –1 ) and slab/trench rollback (0–3 cm yr –1 ) affect mantle flow. Whiskers were used to approximate mineral alignment induced by the flow, as well as to predict directions of seismic anisotropy. We find that dip variations between slab segments generate 3-D flow in the mantle wedge, where the path lines of trenchward moving mantle material above the slab are deflected towards the slab segment with the shallower dip. The degree of path line deflection increases as the difference in slab dip between the segments increases, and, for a fixed dip difference, as slab dip decreases. In cases of slab rollback and large slab dip differences, we observe intrusion of subslab material through the gap and into the wedge. Flow through the gap remains largely horizontal before eventual downward entrainment. Whisker alignment in the wedge flow is largely trench-normal, except near the lateral edges of the slab where toroidal flow dominates. In addition, whisker azimuths located above the slab gap deviate most strongly from trench-normal orientations when slab rollback does not occur. Such flow field complexities are likely sufficient to affect deep melt production and shallow melt delivery. However, none of the experiments produced flow fields that explain the trench-parallel shear wave splitting fast directions observed over broad arc and backarc regions in many subduction zones.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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