6,660 research outputs found

    DNMTs are required for delayed genome instability caused by radiation

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    This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

    Learning organisations: A literature review and critique

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    Approved for Public Release - UnclassifiedA literature review on the Learning Organisation field was conducted, examining the dominant assumptions and creating a solid foundation for the practical application of the learning organisation concept to the Australian Army. In order to examine the literature's dominant assumptions, we asked the following questions: (i) What are the various meanings attributed to learning organisations?; (ii) What sorts of learnings are privileged within the literature?; (iii) What are the key characteristics or "building blocks" that make up a learning organisation? We discovered that the learning organisation construct represents an evolution from bureaucratic and performance-based organisational form to innovative and flexible organisations. In surveying the literature, other factors found to impact on learning organisations included cognitive, social, cultural, technological and structural elements. For example, learning organisations apply increasingly sophisticated understanding of knowledge and personnel management to best exploit their social, intellectual and knowledge capital. In contrast, some factors are not adequately explored in the literature; for example, the significance of power relations, hierarchy and authority on learning within and by organisations has not been fully elucidated. There is an increasing number of studies investigating the direct impact of developing a learner-centric approach on organisational outcomes; the number of studies linking learning to improved organisational performance is growing. There are real, significant and measureable benefits of developing the learning capabilities of an organisation.Steven Talbot, Christina Stothard, Maya Drobnjak and Denise McDowal

    A piloted simulator study on augmentation systems to improve helicopter flying qualities in terrain flight

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    Four basic single-rotor helicopters, one teetering, on articulated, and two hingeless, which were found to have a variety of major deficiencies in a previous fixed-based simulator study, were selected as baseline configurations. The stability and control augmentation systems (SCAS) include simple control augmentation systems to decouple pitch and yaw responses due to collective input and to quicken the pitch and roll control responses; SCAS of rate-command type designed to optimize the sensitivity and damping and to decouple the pitch-roll due to aircraft angular tate; and attitude-command type SCAS. Pilot ratings and commentary are presented as well as performance data related to the task. SCAS control usages and their gain levels associated with specific rotor types are also discussed

    An electron Talbot interferometer

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    The Talbot effect, in which a wave imprinted with transverse periodicity reconstructs itself at regular intervals, is a diffraction phenomenon that occurs in many physical systems. Here we present the first observation of the Talbot effect for electron de Broglie waves behind a nanofabricated transmission grating. This was thought to be difficult because of Coulomb interactions between electrons and nanostructure gratings, yet we were able to map out the entire near-field interference pattern, the "Talbot carpet", behind a grating. We did this using a Talbot interferometer, in which Talbot interference fringes from one grating are moire'-filtered by a 2nd grating. This arrangement has served for optical, X-ray, and atom interferometry, but never before for electrons. Talbot interferometers are particularly sensitive to distortions of the incident wavefronts, and to illustrate this we used our Talbot interferometer to measure the wavefront curvature of a weakly focused electron beam. Here we report how this wavefront curvature demagnified the Talbot revivals, and we discuss applications for electron Talbot interferometers.Comment: 5 pages, 5 figures, updated version with abstrac

    An explanation of the Newman-Janis Algorithm

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    After the original discovery of the Kerr metric, Newman and Janis showed that this solution could be ``derived'' by making an elementary complex transformation to the Schwarzschild solution. The same method was then used to obtain a new stationary axisymmetric solution to Einstein's field equations now known as the Kerr-newman metric, representing a rotating massive charged black hole. However no clear reason has ever been given as to why the Newman-Janis algorithm works, many physicist considering it to be an ad hoc procedure or ``fluke'' and not worthy of further investigation. Contrary to this belief this paper shows why the Newman-Janis algorithm is successful in obtaining the Kerr-Newman metric by removing some of the ambiguities present in the original derivation. Finally we show that the only perfect fluid generated by the Newman-Janis algorithm is the (vacuum) Kerr metric and that the only Petrov typed D solution to the Einstein-Maxwell equations is the Kerr-Newman metric.Comment: 14 pages, no figures, submitted to Class. Quantum Gra

    Photochemistry in the arctic free troposphere: NOx budget and the role of odd nitrogen reservoir recycling

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    The budget of nitrogen oxides (NOx) in the arctic free troposphere is calculated with a constrained photochemical box model using aircraft observations from the Tropospheric O3 Production about the Spring Equinox (TOPSE) campaign between February and May. Peroxyacetic nitric anhydride (PAN) was observed to be the dominant odd nitrogen species (NOy) in the arctic free troposphere and showed a pronounced seasonal increase in mixing ratio. When constrained to observed acetaldehyde (CH3CHO) mixing ratios, the box model calculates unrealistically large net NOx losses due to PAN formation (62pptv/day for May, 1-3km). Thus, given our current understanding of atmospheric chemistry, these results cast doubt on the robustness of the CH3CHO observations during TOPSE. When CH3CHO was calculated to steady state in the box model, the net NOx loss to PAN was of comparable magnitude to the net NOx loss to HNO3 (NO2 reaction with OH) for spring conditions. During the winter, net NOx loss due to N2O5 hydrolysis dominates other NOx loss processes and is near saturation with respect to further increases in aerosol surface area concentration. NOx loss due to N2O5 hydrolysis is sensitive to latitude and month due to changes in diurnal photolysis (sharp day-night transitions in winter to continuous sun in spring for the arctic). Near NOx sources, HNO4 is a net sink for NOx; however, for more aged air masses HNO4 is a net source for NOx, largely countering the NOx loss to PAN, N2O5 and HNO3. Overall, HNO4 chemistry impacts the timing of NOx decay and O3 production; however, the cumulative impact on O3 and NOx mixing ratios after a 20-day trajectory is minimal. © 2003 Elsevier Science Ltd. All rights reserved

    Global atmospheric model for mercury including oxidation by bromine atoms

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    Global models of atmospheric mercury generally assume that gas-phase OH and ozone are the main oxidants converting Hg<sup>0</sup> to Hg<sup>II</sup> and thus driving mercury deposition to ecosystems. However, thermodynamic considerations argue against the importance of these reactions. We demonstrate here the viability of atomic bromine (Br) as an alternative Hg<sup>0</sup> oxidant. We conduct a global 3-D simulation with the GEOS-Chem model assuming gas-phase Br to be the sole Hg<sup>0</sup> oxidant (Hg + Br model) and compare to the previous version of the model with OH and ozone as the sole oxidants (Hg + OH/O<sub>3</sub> model). We specify global 3-D Br concentration fields based on our best understanding of tropospheric and stratospheric Br chemistry. In both the Hg + Br and Hg + OH/O<sub>3</sub> models, we add an aqueous photochemical reduction of Hg<sup>II</sup> in cloud to impose a tropospheric lifetime for mercury of 6.5 months against deposition, as needed to reconcile observed total gaseous mercury (TGM) concentrations with current estimates of anthropogenic emissions. This added reduction would not be necessary in the Hg + Br model if we adjusted the Br oxidation kinetics downward within their range of uncertainty. We find that the Hg + Br and Hg + OH/O<sub>3</sub> models are equally capable of reproducing the spatial distribution of TGM and its seasonal cycle at northern mid-latitudes. The Hg + Br model shows a steeper decline of TGM concentrations from the tropics to southern mid-latitudes. Only the Hg + Br model can reproduce the springtime depletion and summer rebound of TGM observed at polar sites; the snowpack component of GEOS-Chem suggests that 40% of Hg<sup>II</sup> deposited to snow in the Arctic is transferred to the ocean and land reservoirs, amounting to a net deposition flux to the Arctic of 60 Mg a<sup>−1</sup>. Summertime events of depleted Hg<sup>0</sup> at Antarctic sites due to subsidence are much better simulated by the Hg + Br model. Model comparisons to observed wet deposition fluxes of mercury in the US and Europe show general consistency. However the Hg + Br model does not capture the summer maximum over the southeast US because of low subtropical Br concentrations while the Hg + OH/O<sub>3</sub> model does. Vertical profiles measured from aircraft show a decline of Hg<sup>0</sup> above the tropopause that can be captured by both the Hg + Br and Hg + OH/O<sub>3</sub> models, except in Arctic spring where the observed decline is much steeper than simulated by either model; we speculate that oxidation by Cl species might be responsible. The Hg + Br and Hg + OH/O<sub>3</sub> models yield similar global budgets for the cycling of mercury between the atmosphere and surface reservoirs, but the Hg + Br model results in a much larger fraction of mercury deposited to the Southern Hemisphere oceans

    Characterization of aerosol associated with enhanced small particle number concentrations in a suburban forested environment

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    Two elevated particle number/mass growth events associated with Aitken‐mode particles were observed during a sampling campaign (13–29 September 2004) at the Duke University Free‐Air CO2 Enrichment facility, a forested field site located in suburban central North Carolina. Aerosol growth rates between 1.2 and 4.9 nm hr−1 were observed, resulting in net increases in geometric mean diameter of 21 and 37 nm during events. Growth was dominated by addition of oxidized organic compounds. Campaign‐average aerosol mass concentrations measured by an Aerodyne quadrupole aerosol mass spectrometer (Q‐AMS) were 1.9 ± 1.6 (σ), 1.6 ± 1.9, 0.1 ± 0.1, and 0.4 ± 0.4 μg m−3 for organic mass (OM), sulfate, nitrate, and ammonium, respectively. These values represent 47%, 40%, 3%, and 10%, respectively, of the measured submicron aerosol mass. Based on Q‐AMS spectra, OM was apportioned to hydrocarbon‐like organic aerosol (HOA, likely representing primary organic aerosol) and two types of oxidized organic aerosol (OOA‐1 and OOA‐2), which constituted on average 6%, 58%, and 36%, respectively, of the apportioned OM. OOA‐1 probably represents aged, regional secondary organic aerosol (SOA), while OOA‐2 likely reflects less aged SOA. Organic aerosol characteristics associated with the events are compared to the campaign averages. Particularly in one event, the contribution of OOA‐2 to overall OM levels was enhanced, indicating the likelihood of less aged SOA formation. Statistical analyses investigate the relationships between HOA, OOA‐1, OOA‐2, other aerosol components, gas‐phase species, and meteorological data during the campaign and individual events. No single variable clearly controls the occurrence of a particle growth event
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