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  • 1
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    Mechanism of CRISPR-RNA guided recognition of DNA targets in Escherichia coli (2015)
    Oxford University Press
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    Publication Date: 2015-09-30
    Description: In bacteria and archaea, short fragments of foreign DNA are integrated into Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci, providing a molecular memory of previous encounters with foreign genetic elements. In Escherichia coli , short CRISPR-derived RNAs are incorporated into a multi-subunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Recent structures of Cascade capture snapshots of this seahorse-shaped RNA-guided surveillance complex before and after binding to a DNA target. Here we determine a 3.2 Å x-ray crystal structure of Cascade in a new crystal form that provides insight into the mechanism of double-stranded DNA binding. Molecular dynamic simulations performed using available structures reveal functional roles for residues in the tail, backbone and belly subunits of Cascade that are critical for binding double-stranded DNA. Structural comparisons are used to make functional predictions and these predictions are tested in vivo and in vitro . Collectively, the results in this study reveal underlying mechanisms involved in target-induced conformational changes and highlight residues important in DNA binding and protospacer adjacent motif recognition.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Soft X-ray irradiance measured by the Solar Aspect Monitor on the Solar Dynamic Observatory Extreme ultraviolet Variability Experiment (2016)
    Wiley
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    Publication Date: 2016-04-09
    Description: The Solar Aspect Monitor (SAM) is a pinhole camera on the Extreme-ultraviolet Variability Experiment (EVE) aboard the Solar Dynamics Observatory (SDO). SAM projects the solar disk onto the CCD through a metallic filter designed to allow only solar photons shortward of 7 nm to pass. Contamination from energetic particles and out-of-band irradiance is, however, significant in the SAM observations. We present a technique for isolating the 0.01–7 nm integrated irradiance from the SAM signal to produce the first results of broadband irradiance for the time period from May 2010 to May 2014. The results of this analysis agree with a similar data product from EVE's EUV SpectroPhotometer (ESP) to within 25%. We compare our results with measurements from the Student Nitric Oxide Explorer (SNOE) Solar X-ray Photometer (SXP) and the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) Solar EUV Experiment (SEE) at similar levels of solar activity. We show that the full-disk SAM broadband results compare well to the other measurements of the 0.01–7 nm irradiance. We also explore SAM's capability toward resolving spatial contribution from regions of solar disk in irradiance and demonstrate this feature with a case study of several strong flares that erupted from active regions on March 11, 2011.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
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    Is a high-altitude meteorological analysis necessary to simulate thermosphere-stratosphere coupling? (2015)
    Wiley
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    Publication Date: 2015-09-25
    Description: We compare simulations of mesospheric tracer descent in the winter and spring of 2009 with two versions of the Whole Atmosphere Community Climate Model (WACCM), both with specified dynamics (SD). One is constrained with data from the Modern Era Retrospective Analysis for Research and Applications (MERRA) which extends from 0–50 km, the other uses the Navy Operational Global Atmospheric Prediction System- Advanced Level Physics High Altitude (NOGAPS-ALPHA) which extends up to 92 km. By comparison with Solar Occultation For Ice Experiment (SOFIE) data we show that constraining WACCM to NOGAPS-ALPHA yields a dramatic improvement in the simulated descent of enhanced nitric oxide (NO) and very low methane (CH 4 ). We suggest that constraining to NOGAPS-ALPHA compensates for an underestimate of non-orographic gravity wave drag in WACCM. Other possibilities, such as missing energetic particle precipitation or underestimated eddy diffusion are less likely for the Arctic winter and spring of 2009.
    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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  • 4
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    The roles of temperature and water vapor at different stages of the polar mesospheric cloud season (2012)
    Wiley
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    Publication Date: 2012-02-23
    Description: Temperature, or alternatively, saturation vapor pressure (PSAT), dominantly controls the polar mesospheric cloud (PMC) seasonal onset and termination, characterized by a strong anticorrelated relationship between the Solar Occultation for Ice Experiment (SOFIE)-observed PMC frequency and PSAT on intraseasonal time scales. SOFIE is highly sensitive to weak clouds and can obtain a nearly full spectrum of PMCs. Both the SOFIE PMC frequency and PSAT indicate a rapid onset and termination of the season. Compared to PSAT, the water vapor partial pressure (PH2O) exhibits only a slight increase from before to after the start of the season. We are able to use the PSAT daily minimum and two averaged PH2O levels taken before and after the solstice, respectively, to estimate the start and end days of the PMC season within 1–2 days uncertainty. SOFIE ice mass density and its relationship to PH2O and PSAT are examined on intraseasonal scales and for two extreme conditions, i.e., strong and weak cloud cases. In the strong cloud case, such as those bright clouds that occur during the core of the season, PH2O far exceeds PSAT and dominantly controls the ice mass density variation, while in the weak cloud case, such as those clouds that occur at the start and end of the season, PH2O and PSAT have comparable magnitudes, vary in concert, and have similar effects on the ice mass density variation. These results suggest that the long-term brightness trends reported by DeLand et al. (2007) are primarily driven by changes in water vapor (H2O), not temperature.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 5
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    On the seasonal onset of polar mesospheric clouds and the breakdown of the stratospheric polar vortex in the Southern Hemisphere (2011)
    Wiley
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    Publication Date: 2011-09-22
    Description: Southern Hemisphere (SH) polar mesospheric clouds (PMCs), also known as noctilucent clouds, have been observed to be more variable and, in general, dimmer than their Northern Hemisphere (NH) counterparts. The precise cause of these hemispheric differences is not well understood. This paper focuses on one aspect of the hemispheric differences: the timing of the PMC season onset. Observations from the Aeronomy of Ice in the Mesosphere satellite indicate that in recent years the date on which the PMC season begins varies much more in the SH than in the NH. Using the Canadian Middle Atmosphere Model, we show that the generation of sufficiently low temperatures necessary for cloud formation in the SH summer polar mesosphere is perturbed by year-to-year variations in the timing of the late-spring breakdown of the SH stratospheric polar vortex. These stratospheric variations, which persist until the end of December, influence the propagation of gravity waves up to the mesosphere. This adds a stratospheric control to the temperatures in the polar mesopause region during early summer, which causes the onset of PMCs to vary from one year to another. This effect is much stronger in the SH than in the NH because the breakdown of the polar vortex occurs much later in the SH, closer in time to the PMC season.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    A multi tracer analysis of thermosphere to stratosphere descent triggered by the 2013 Stratospheric Sudden Warming (2014)
    Wiley
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    Publication Date: 2014-05-26
    Description: Arctic winter observations in 2013 by the Solar Occultation for Ice Experiment (SOFIE) show significant transport from the lower-thermosphere to the stratosphere of air enriched in nitric oxide, but depleted in water and methane. The transport is triggered by the Stratospheric Sudden Warming (SSW) on January 11 and is continuously tracked for over three months. Ultimately, evidence for lower thermospheric air is seen at 40 km in mid-April. Area integrated NO fluxes are compared with previous events in 2004, 2006, and 2009, to show that this event is the 2 nd largest in the past 10 years. The SOFIE data are combined with a meteorological analysis to infer descent rates from 40–90 km. The descent profile initially peaks near 75 km, shifting downward by approximately 5 km per 10 days. Our work demonstrates the utility of SOFIE tracer measurements in diagnosing vertical transport from the stratosphere to the edge of space.
    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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  • 7
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    Northern PMC brightness zonal variability and its correlation with temperature and water vapor (2014)
    Wiley
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    Publication Date: 2014-02-07
    Description: Polar mesospheric clouds (PMCs) measured by the Cloud Imaging and Particle Size instrument on the AIM satellite show strong zonal asymmetries, with prominent planetary scale variations. The correlations between zonal variations of cloud brightness and temperature or water vapor (H 2 O) are determined in different stages of the PMC season. Aura Microwave Limb Sounder (MLS) measured temperature and water vapor are used in the analysis. A 0-D PMC model was used to interpret the observation. Analyses of all days of the five northern seasons from 2007 to 2011 indicate that temperature and albedo daily zonal variations are anti-correlated in the season start and end, whereas in the core of the season the correlation is relatively poor. The albedo and H 2 O correlation in the zonal direction is poor throughout the season. 0-D model physics indicates that when clouds are weaker, or the environment is warmer and drier, temperature plays an increasingly important role in determining the cloud ice mass variation, which explains the stronger correlation of temperature and albedo at the start and end of the season. Water vapor takes a strong role in determining the ice mass variation in the core of the season when the clouds are stronger and environment is colder and wetter. However, on a daily basis the H 2 O depletion associated with the ice production will lead to significant shift of the ice maxima and “post-ice” H 2 O maxima in the zonal direction, which leads to the poor correlation between the observed H 2 O and albedo.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 8
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    Strand-specific postreplicative processing of mammalian telomeres (2001)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2001-09-29
    Description: Telomeres are specialized nucleoprotein structures that stabilize the ends of linear eukaryotic chromosomes. In mammalian cells, abrogation of telomeric repeat binding factor TRF2 or DNA-dependent protein kinase (DNA-PK) activity causes end-to-end chromosomal fusion, thus establishing an essential role for these proteins in telomere function. Here we show that TRF2-mediated end-capping occurs after telomere replication. The postreplicative requirement for TRF2 and DNA-PKcs, the catalytic subunit of DNA-PK, is confined to only half of the telomeres, namely, those that were produced by leading-strand DNA synthesis. These results demonstrate a crucial difference in postreplicative processing of telomeres that is linked to their mode of replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, S M -- Cornforth, M N -- Kurimasa, A -- Chen, D J -- Goodwin, E H -- AG-917709/AG/NIA NIH HHS/ -- CA50519/CA/NCI NIH HHS/ -- CA76260/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 28;293(5539):2462-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11577237" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Line ; Chromatids/physiology/ultrastructure ; Chromosomes/physiology/ultrastructure ; *DNA Replication ; DNA-Activated Protein Kinase ; DNA-Binding Proteins/genetics/*metabolism ; Humans ; In Situ Hybridization ; Mice ; Mitosis ; Mutation ; Nuclear Proteins ; Protein-Serine-Threonine Kinases/deficiency/metabolism ; Telomere/*metabolism ; Telomeric Repeat Binding Protein 2 ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    New AIM/CIPS Global Observations of Gravity Waves near 50-55 km (2017)
    Wiley
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    Publication Date: 2017-06-28
    Description: This paper describes a new data set from the Aeronomy of Ice in the Mesosphere (AIM) Cloud Imaging and Particle Size (CIPS) instrument, from which gravity waves (GWs) at an altitude of 50-55 km can be inferred. CIPS is sensitive to GWs with horizontal wavelengths from ~15-600 km and vertical wavelengths longer than 15 km. Several examples of GWs in CIPS observations are shown, including waves associated with the Andes mountains, island topography, convection, the polar night jet, and the tropospheric jet stream. GW signatures in the CIPS data are shown to agree well with near-coincident but lower-altitude measurements from the Atmospheric InfraRed Sounder (AIRS) in June of 2016. Results suggest the power of combining CIPS measurements with those from other instruments to investigate GW filtering and propagation. The CIPS data set opens new areas of inquiry, enabling comprehensive investigations of GWs in the middle atmosphere on a near-global scale.
    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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  • 10
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    Molecular characterisation of murine acute myeloid leukaemia induced by 56Fe ion and 137Cs gamma ray irradiation (2012)
    Oxford University Press
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    Publication Date: 2012-12-20
    Description: Exposure to sparsely ionising gamma- or X-ray irradiation is known to increase the risk of leukaemia in humans. However, heavy ion radiotherapy and extended space exploration will expose humans to densely ionising high linear energy transfer (LET) radiation for which there is currently no understanding of leukaemia risk. Murine models have implicated chromosomal deletion that includes the hematopoietic transcription factor gene, PU.1 (Sfpi1) , and point mutation of the second PU.1 allele as the primary cause of low-LET radiation-induced murine acute myeloid leukaemia (rAML). Using array comparative genomic hybridisation, fluorescence in situ hybridisation and high resolution melt analysis, we have confirmed that biallelic PU.1 mutations are common in low-LET rAML, occurring in 88% of samples. Biallelic PU.1 mutations were also detected in the majority of high-LET rAML samples. Microsatellite instability was identified in 42% of all rAML samples, and 89% of samples carried increased microsatellite mutant frequencies at the single-cell level, indicative of ongoing instability. Instability was also observed cytogenetically as a 2-fold increase in chromatid-type aberrations. These data highlight the similarities in molecular characteristics of high-LET and low-LET rAML and confirm the presence of ongoing chromosomal and microsatellite instability in murine rAML.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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