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  • 1
    Publication Date: 2013-09-08
    Description: [1]  Different solutions have been proposed to solve the ‘faint young Sun problem’, defined by the fact that the Earth was not fully frozen during the Archean despite the fainter Sun. Most previous studies were performed with simple 1D radiative convective models and did not account well for the clouds and ice-albedo feedback or the atmospheric and oceanic transport of energy. We apply a Global Climate Model (GCM) to test the different solutions to the faint young Sun problem. We explore the effect of greenhouse gases (CO 2 and CH 4 ), atmospheric pressure, cloud droplet size, land distribution and Earth's rotation rate. We show that, neglecting organic haze, 100 mbars of CO 2 with 2 mbars of CH 4 at 3.8 Ga and 10 mbars of CO 2 with 2 mbars of CH 4 at 2.5 Ga allow a temperate climate (mean surface temperature between 10 °C and 20 °C). Such amounts of greenhouse gases remain consistent with the geological data. Removing continents produces a warming lower than +4 °C. The effect of rotation rate is even more limited. Larger droplets (radii of 17  µm versus 12  µm ) and a doubling of the atmospheric pressure produce a similar warming of around +7 °C. In our model, ice-free waterbelts can be maintained up to 25° N/S with less than 1 mbar of CO 2 and no methane. An interesting cloud feedback appears above cold oceans, stopping the glaciation. Such a resistance against full glaciation tends to strongly mitigate the faint young Sun problem.
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  • 2
    Publication Date: 2013-09-08
    Description: [1]  The Cross-track Infrared Sounder (CrIS) is the high spectral resolution spectroradiometer on the Suomi National Polar-Orbiting Partnership (NPP) satellite, providing operational observations of top-of-atmosphere thermal infrared radiance spectra for weather and climate applications. This paper describes the CrIS radiometric calibration uncertainty based on pre-launch and on-orbit efforts to estimate calibration parameter uncertainties, and provides example results of recent post-launch validation efforts to assess the predicted uncertainty. Pre-launch Radiometric Uncertainty (RU) estimates computed for the laboratory test environment are less than ~0.2 K 3-sigma for blackbody scene temperatures above 250 K, with primary uncertainty contributions from the calibration blackbody temperature, calibration blackbody reflected radiance terms and detector nonlinearity. Variability of the pre-launch RU among the longwave band detectors and midwave band detectors is due to different levels of detector nonlinearity. A methodology for on-orbit adjustment of nonlinearity correction parameters to reduce the overall contribution to RU and to reduce FOV-to-FOV variability is described. The resulting on-orbit RU estimates for Earth view spectra are less than 0.2 K 3-sigma in the midwave and shortwave bands, and less than 0.3 K 3-sigma in the longwave band. Post-launch validation efforts to assess the radiometric calibration of CrIS are underway; validation results to date indicate that the on-orbit RU estimates are representative. CrIS radiance products are expected to reach “Validated” status in early 2014.
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  • 3
    Publication Date: 2013-09-08
    Description: [1]  An extended Tracking Radar Echo by Correlation (TREC) technique, called T-TREC technique, has been developed recently to retrieve horizontal circulations within tropical cyclones (TCs) from single Doppler radar reflectivity ( Z ) and radial velocity ( V r , when available) data. This study explores, for the first time, the assimilation of T-TREC-retrieved winds for a landfalling typhoon, Meranti (2010), into a convection-resolving model, the WRF (Weather Research and Forecasting). The T-TREC winds or the original V r data from a single coastal Doppler radar are assimilated at the single time using the WRF 3DVAR, at 8, 6, 4 and 2 hours before the landfall of typhoon Meranti. In general, assimilating T-TREC winds results in better structure and intensity analysis of Meranti than directly assimilating V r data. The subsequent forecasts for the track, intensity, structure and precipitation are also better, although the differences becomes smaller as the V r data coverage improves when the typhoon gets closer to the radar. The ability of the T-TREC retrieval in capturing more accurate and complete vortex circulations in the inner-core region of TC is believed to be the primary reason for its superior performance over direct assimilation of V r data; for the latter, the data coverage is much smaller when the TC is far away and the cross-beam wind component is difficult to analyze accurately with 3DVAR method.
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  • 4
    Publication Date: 2013-09-08
    Description: [1]  Given its large population, vigorous and water-intensive agricultural industry, and important ecological resources, the western United States presents a valuable case study for examining potential near-term changes in regional hydroclimate. Using a high-resolution, hierarchical, five-member ensemble modeling experiment that includes a global climate model (CCSM), a regional climate model (RegCM), and a hydrological model (VIC), we find that increases in greenhouse forcing over the next three decades result in an acceleration of decreases in spring snowpack and a transition to a substantially more liquid-dominated water resources regime. These hydroclimatic changes are associated with increases in cold-season days above freezing and decreases in the cold-season snow-to-precipitation ratio. The changes in the temperature and precipitation regime in turn result in shifts toward earlier snowmelt, baseflow, and runoff dates throughout the region, as well as reduced annual and warm-season snowmelt and runoff. The simulated hydrologic response is dominated by changes in temperature, with the ensemble members exhibiting varying trends in cold-season precipitation over the next three decades, but consistent negative trends in cold-season freeze days, cold-season snow-to-precipitation ratio, and April 1 st snow water equivalent. Given the observed impacts of recent trends in snowpack and snowmelt runoff, the projected acceleration of hydroclimatic change in the western U.S. has important implications for the availability of water for agriculture, hydropower and human consumption, as well as for the risk of wildfire, forest die-off, and loss of riparian habitat.
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  • 5
    Publication Date: 2013-09-10
    Description: [1]  The consequences of different Quasi-Biennial Oscillation (QBO) nudging widths on stratospheric dynamics and chemistry are analyzed by comparing two model simulations with NCAR's WACCM model where the width of the QBO is varied between 22° and 8.5°N and S. The sensitivity to the nudging width is strongest in Northern Hemisphere (NH) winter where the Holton-Tan effect in the polar stratosphere, i.e., stronger zonal mean winds during QBO west phases, is enhanced for the wider compared to the narrower nudging case. The differences between QBO west and east conditions for the two model experiments can be explained with differences in wave propagation, wave-mean flow interaction and the residual circulation. In the wider nudging case a divergence anomaly in the mid-latitude upper stratosphere/lower mesosphere occurs together with an equatorward anomaly of the residual circulation. This seems to result in a strengthening of the meridional temperature gradient and hence a significant strengthening of the polar night jet (PNJ). In the narrower nudging case these circulation changes are weaker and not statistically significant, consistent with a weaker and less significant impact on the PNJ. Chemical tracers like ozone, water vapour and methane react accordingly. From a comparison of westerly minus easterly phase composite differences in the model to reanalysis and satellite data we conclude that the standard WACCM configuration (QBO22) generates more realistic QBO effects in stratospheric dynamics and chemistry during NH winter. Our study also confirms the importance of the secondary mean meridional circulation associated with the QBO for the Holton-Tan effect.
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  • 6
    Publication Date: 2013-09-12
    Description: [1]  The microphysical properties of ice fog were measured at two sites during a small IOP in January and February of 2012 in the Interior Alaska. The NCAR Video Ice Particle Sampler (VIPS) probe and formvar (polyvinyl formal) coated microscope slides were used to sample airborne ice particles at two polluted sites in the Fairbanks region. Both sites were significantly influenced by anthropogenic emission and additional water vapor from nearby open water power plant cooling ponds. Measurements show that ice fog particles were generally droxtal-shaped (faceted, quasi-spherical) for sub-10 µm particles, while plate shaped crystals were the most frequently observed particles between 10 and 50 µm. A visibility cutoff of 3 kilometers was used to separate ice fog events from other observations which were significantly influenced by larger (50–150 µm) diamond dust particles. [2]  The purpose of this study is to more realistically characterize ice fog microphysical properties in order to facilitate better model predictions of the onset of ice fog in polluted environments. Parameterizations for mass and projected area are developed and used to estimate particle terminal velocity. Dimensional characteristics are based on particle geometry and indicated that ice fog particles have significantly lower density values than water droplets as well as reduced cross-sectional areas, the net result being that terminal velocities are estimated to be less than half the value of those calculated for water droplets. Particle size distributions are characterized using gamma functions and have a shape factor (μ) of between −0.5 and −1.0 for polluted ice fog conditions.
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  • 7
    Publication Date: 2013-09-14
    Description: [1]  In our recent paper [6], the sensitivity of infrasound to the upper atmosphere is investigated using impulsive signals from the Tungurahua volcano in Ecuador. We reported on the coherent variability of thermospheric travel times, with periods equal to those of the tidal harmonics. Moreover, it was shown that the error in predicted thermospheric travel time is in accord with typical uncertainties in the upper atmospheric wind speed models. Given the observed response of the infrasound celerities to upper atmospheric tidal variability, it was suggested that infrasound observations may be used to reduce uncertainty in the knowledge of the atmospheric specifications in the upper atmosphere. In this paper, we discuss the estimation of upper atmospheric wind model updates from the infrasound data described in the aforementioned paper. The parameterization of the model space by empirical orthogonal functions is described; it is found that the wind model in the upper mesosphere and lower thermosphere can be described by a four-parameter model. Due to the small dimensionality of the model space, a grid search method can be used to solve the inverse problem. A Bayesian method is used to assess the uncertainty in the inverse solution given the a priori uncertainty in the data and model spaces and the non-linearity of the inverse problem at hand. We believe that this is the first study in which such methods are applied to real infrasound data, allowing for a rigorous analysis of this inverse problem. It is found that the complexity of the a posteriori model distribution increases for a larger dimensional model space and larger uncertainties in the data. A case study is presented in which the non-linear propagation from source to receiver is simulated using an updated wind model and non-linear ray theory. As non-linear propagation effects further constrain the propagation path, this is a way to check the physical self-consistency of the travel time inversion approach. We obtain excellent agreement between the simulated and observed waveforms.
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  • 8
    Publication Date: 2013-09-14
    Description: [1]  Thirty years of balloon-borne measurements over Boulder (40 ∘ N, 105 ∘ W) are used to investigate the water vapor trend in the tropopause region. This analysis extends previously published trends, usually focusing on altitudes greater than 16km, to lower altitudes. Two new concepts are applied: 1) Trends are presented in a thermal tropopause (TP) relative coordinate system from − 2km below to 10km above the TP. 2) Sonde profiles are selected according to TP height. Tropical (TP z  〉 14km), extratropical (TP z  〈 12km), and transitional air mass types (12km 〈 TP z  〈 14km), reveal three different water vapor reservoirs. The analysis based on these concepts reduces the dynamically–induced water vapor variability at the TP and principally favors refined water vapor trend studies in the upper troposphere and lower stratosphere. Nonetheless, this study showshow uncertain trends are at altitudes −2 to + 4km around the TP. This uncertainty in turn has an influence on the uncertainty and interpretation of water vapor radiative effects at the TP, which are locally estimated for the 30 year period to be of uncertain sign. The much discussed decrease in water vapor at the beginning of 2001 is not detectable between −2 to 2km around the TP. On lower stratospheric isentropes, the water vapor change at the beginning of 2001 is more intense for extratropical than for tropical air mass types. This suggests a possible link with changing dynamics above the jet stream such as changes in the shallow branch of the Brewer–Dobson circulation.
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  • 9
    Publication Date: 2013-09-16
    Description: [1]  Retrievals of sulfur dioxide (SO 2 ) from space-based spectrometers are in a relatively early stage of development. Factors such as interference between ozone and SO 2 in the retrieval algorithms often lead to errors in the retrieved values. Measurements from the Ozone Monitoring Instrument (OMI), SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY), and Global Ozone Monitoring Experiment −2 (GOME-2) satellite sensors, averaged over a period of several years, were used to identify locations with elevated SO 2 values and estimate their emission levels. About 30 such locations, detectable by all three sensors and linked to volcanic and anthropogenic sources, were found, after applying low- and high- spatial frequency filtration designed to reduce noise and bias and to enhance weak signals to SO 2 data from each instrument. Quantitatively, the mean amount of SO 2 in the vicinity of the sources, estimated from the three instruments is in general agreement. However, it's better spatial resolution makes it possible for OMI to detect smaller sources and with additional more detail as compared to the other two instruments. Over some regions of China, SCIAMACHY and GOME-2 data show mean SO 2 values that are almost 1.5 times higher than those from OMI but the suggested spatial filtration technique largely reconciles these differences.
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  • 10
    Publication Date: 2013-09-17
    Description: [1]  Dust is an important indicator of climate change. In paleo-climate research, sediments bearing signals of dust deposition offer a rich archive for climate-change history. However, the dust-climate link is very complex due to the various direct and indirect feedbacks in the Earth system. In this study, we examine two issues: (1) given the recent global warming, what are the dust variations, both globally and in key dust regions? and, (2) what are the climate drivers behind the variations? Using synoptic data for the period 1974-2012, we analyzed the global trend of dust frequency and visibility-derived dust concentrations and their characteristics in key dust regions, including North Africa, the Middle East, Southwest Asia, Northeast Asia, South America and Australia. We also examined the likely climate drivers for dust variations in the different regions by computing the correlations between the time series of dust and of major climate indices – the MEI (Multivariate El Niño/Southern Oscillation Index), NAO (North Atlantic Oscillation) and AMO (Atlantic Multi-decadal Oscillation). It was found that over the period 1984–2012, the global-mean (excluding North America and Europe) near-surface dust concentration decreased at 1.2% yr -1 . This decrease is mainly due to reduced dust activities in North Africa, accompanied by reduced activities in Northeast Asia, South America, and South Africa. A significant negative correlation between Saharan dust and AMO was detected and it seems reasonable to suggest that under present climate, the global dust trend is determined by the climate systems governing the Atlantic and North African regimes.
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  • 11
    Publication Date: 2013-09-17
    Description: [1]  We show measurements of middle atmospheric water vapor as measured by two ground-based Water Vapor Millimeter-wave Spectrometer (WVMS) instruments, and three satellite-based instruments: the Aura Microwave Limb Sounder (MLS), the Atmospheric Chemistry Experiment (ACE), and the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). We also show CH 4 measurements from the MIPAS and ACE instruments and use these to help interpret the H 2 O variations. We find that interannual changes in stratospheric H 2 O of ~0.5 ppmv, observed from Table Mountain, California at 26 km and 40 km from 2010–2012, are caused primarily by dynamically driven changes in CH 4 during this period. The interannual variations in H 2 O observed over Mauna Loa, Hawaii, are shown to be quite similar to the average variations observed over 50 o S-50 o N in the lower mesosphere, thus we conclude that a single ground-based microwave instrument can provide a useful estimate of interannual globally averaged lower mesospheric H 2 O variations, even when such changes are as small as ~0.2-0.3 ppmv. We find that the increase of ~0.2-0.3 ppmv in H 2 O in the lower mesosphere since 2006 is qualitatively consistent with an increase in tropical tropopause temperature since ~2001.
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  • 12
    Publication Date: 2013-09-17
    Description: [1]  An adjoint version of the HARC neighborhood air quality model with 200 m horizontal resolution, coupled offline to the QUIC-URB fast response urban wind model, was used to perform 4D variational (4Dvar) inverse modeling of an industrial release of formaldehyde (HCHO) and sulfur dioxide (SO 2 ) in Texas City, Texas during the 2009 Study of Houston Atmospheric Radical Precursors (SHARP). The source attribution was based on real-time observations by the Aerodyne mobile laboratory and a high resolution 3D digital model of the emitting petrochemical complex and surrounding urban canopy. The inverse model estimate of total primary HCHO emitted during the incident agrees very closely with independent remote sensing estimates based on both Imaging and Multi-Axis Differential Optical Absorption Spectroscopy (DOAS). Whereas a previous analysis of Imaging DOAS data attributed the HCHO release to a Fluidized Catalytic Cracking Unit (FCCU), the HARC model attributed most of the HCHO and SO 2 release to a neighboring hydrotreater unit that desulfurizes the feed to the FCCU. Other facilities implicated by the source attribution were ultraformer and distillate desulfurization units and two flares. The inferred HCHO-to-SO 2 molar emission ratio was similar to that computed directly from ambient air measurements during the release. The model-estimated HCHO-to-CO molar emission ratio for combustion units with significant inferred emissions ranged from 2% to somewhat less than 7%, consistent with other observationally-based estimates obtained during SHARP. A model sensitivity study demonstrated that the inclusion of urban morphology has a significant, but not critical, impact on the source attribution.
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  • 13
    Publication Date: 2013-09-17
    Description: [1]  Carbonaceous aerosols have the potential to impact climate directly through absorption of incoming solar radiation and indirectly by affecting cloud and precipitation. To quantify this impact, recent modeling studies have made great efforts to simulate both the spatial and temporal distribution of carbonaceous aerosol's optical properties and associated radiative forcing. This study makes the first observationally constrained assessment of the direct radiative forcing of carbonaceous aerosols over California. By exploiting multiple observations (including ground sites and satellites), we constructed the distribution of aerosol optical depths and aerosol absorption optical depths (AAOD) over California for a ten-year period (2000–2010). We partitioned the total solar absorption into individual contributions from elemental carbon (EC), organic carbon (OC), and dust aerosols, using a newly developed scheme. Our results show that AAOD due to carbonaceous aerosols (EC and OC) at 440 nm was 50%–200% larger than natural dust, with EC contributing the bulk (70%–90%). Observationally constrained EC absorption agrees reasonably well with estimates from global and regional chemical transport models, but the models underestimate the OC AAOD by at least 50%. We estimated that the top of the atmosphere (TOA) forcing from carbonaceous aerosols was 0.7 W/m 2 and the TOA forcing due to OC was close to zero. The atmospheric heating of carbonaceous aerosol was 2.2–2.9 W/m 2 , of which EC contributed about 80–90%. We estimated the atmospheric heating of OC at 0.1–0.4 W/m 2 , larger than model simulations. EC reduction over the last two decades may have caused a surface brightening of 1.5–3.5 W/m 2 .
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  • 14
    Publication Date: 2013-09-17
    Description: [1]  The tropospheric seasonal cycles of N 2 O, CFC-11 (CCl 3 F), and CFC-12 (CCl 2 F 2 ) are influenced by atmospheric dynamics. The interannually varying summertime minima in mole fractions of these trace gases have been attributed to interannual variations in mixing of stratospheric air (depleted in CFCs and N 2 O) with tropospheric air with a few months lag. The amount of wave activity that drives the stratospheric circulation and influences the winter stratospheric jet and subsequent mass transport across the tropopause appears to be the primary cause of this interannual variability. We relate the observed seasonal minima of species at three Northern Hemisphere sites (Mace Head, Ireland; Trinidad Head, USA and Barrow, Alaska) with the behavior of the winter stratospheric jet. As a result, a good correlation is obtained between zonal winds in winter at 10 hPa, 58 o N-68 o N and the de-trended seasonal minima in the stratosphere-influenced tracers. For these three tracers, individual Pearson correlation coefficients (r) between 0.51 and 0.71 were found, with overall correlations of between 0.67 and 0.77 when ‘composite species’ were considered. Finally we note that the long-term observations of CFCs and N 2 O in the troposphere provide an independent monitoring method complementary to satellite data. Furthermore they could provide a useful observational measure of the strength of stratosphere-troposphere exchange and thus, could be used to monitor any long-term trend in the Brewer-Dobson Circulation which is predicted by climate models to increase over the coming decades.
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  • 15
    Publication Date: 2013-09-19
    Description: [1]  Monthly temperature and precipitation data from 41 global climate models (GCMs) of the Coupled Model Intercomparison Project Phase 5 (CMIP5) were compared to observations for the 20 th century, with a focus on the United States Pacific Northwest (PNW) and surrounding region. A suite of statistics, or metrics, was calculated, that included correlation and variance of mean seasonal spatial patterns, amplitude of seasonal cycle, diurnal temperature range, annual- to decadal- scale variance, long-term persistence, and regional teleconnections to ENSO. Performance, or credibility, was assessed based on the GCMs’ abilities to reproduce the observed metrics. GCMs were ranked in their credibility using two methods. The first simply treated all metrics equally. The second method considered two properties of the metrics: 1) redundancy of information (dependence) among metrics, and 2) confidence in the reliability of an individual metric for accurately ranking models. Confidence was related to how robust the estimate of the metric was to ensemble size, given that for most of the models only a small number of ensemble members (i.e. realizations of the 20 th century) were available. A cursory comparison with 24 CMIP3 models revealed few differences between the two generations of models with respect to the statistics analyzed.
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  • 16
    Publication Date: 2013-09-19
    Description: [1]  In this paper, the effects of temperature, pressure, winds, moisture and molecular content on the propagation of blast waves at high altitudes are investigated. These cause refractions and attenuations which modify the recorded ground overpressures from the ideal predictions. By coupling these effects together, the non-ideal corrections to the overpressures are estimated by applying approximations which are dependent on the angle of propagation of the blast wave.
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  • 17
    Publication Date: 2013-09-19
    Description: [1]  The most severe thunderstorms, producing extreme precipitation, occur over subtropical and midlatitude regions. Atmospheric conditions conducive to organized, intense thunderstorms commonly involve the coupling of a low-level jet (LLJ) with a synoptic short wave. The midlatitude synoptic activity is frequently modulated by the circumglobal teleconnection (CGT) – in which meridional gradients of the jet stream act as a guide for short Rossby waves. Previous research has linked extreme precipitation events with either the CGT or the LLJ, but has not linked the two circulation features together. In this study, a circulation-based index was developed by combining (a) the degree of the CGT and LLJ coupling, (b) the extent to which this CGT-LLJ coupling connects to regional precipitation, and (c) the spatial correspondence with the CGT (short-wave) trending pattern over the most recent 32 years (1979-2010). Four modern-era global reanalyses, in conjunction with four gridded precipitation datasets, were utilized to minimize spurious trends. The results are suggestive of a link between several recent extreme precipitation events and the CGT/LLJ trends, including those leading to the 2008 Midwest flood in U.S., the 2011 tornado outbreaks in southeastern U.S., the 2010 Queensland flood in northeastern Australia and the 2010 Pakistan flood. Moreover, an analysis of three CMIP5 models from the historical experiments points to the role of greenhouse gases in forming the CGT trends during the warm season.
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  • 18
    Publication Date: 2013-09-21
    Description: [1]  Mineral aerosols are produced during the erosion of soils by wind and are a common component of the total atmospheric particle load (dust) in arid and semi-arid regions. The size of these particles can vary widely from clay particles less than 2 µm to larger silt and sand-sized particles that can exceed 50 µm in diameter. In this study, we present two continuous records of total suspended particle (TSP) concentrations at sites in Mesa Verde and Canyonlands National Parks in Colorado and Utah, USA, respectively, and compare those values to measurements of fine and coarse particle concentrations made from nearby IMPROVE-network samplers. Average annual concentrations of TSP at Mesa Verde were 90 µg m -3 in 2011 and at Canyonlands were 171 µg m -3 in 2009, 113 µg m -3 in 2010, and 134 µg m -3 in 2011. In comparison, annual concentrations of fine (diameter of 2.5 µm and below) and coarse (2.5-10 µm diameter) particles at these sites were well below 10 µg m -3 in all years. The high concentrations of TSP appear to be the result of regional dust storms that result in elevated concentrations of very coarse particles greater than 10 µm in diameter. These conditions regularly occur from early spring until early fall with two-week mean TSP periodically in excess of 200 µg m -3 at Canyonlands. Measurement of particle sizes embedded on filters indicates that the median particle size of all particles varies between approximately 10 µm in winter and 40 µm during the spring dust-storm season. These persistently elevated concentrations of large particles indicate that regional dust emission as dust storms and events are important determinants of air quality in this region.
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  • 19
    Publication Date: 2013-09-21
    Description: [1]  Nitrogen oxide radicals (NO x ) produced by lightning are natural precursors for the production of the dominant tropospheric oxidants, OH and ozone. Observations of the interannual variability (IAV) of tropical ozone and of global mean OH (from the methylchloroform proxy) offer a window for understanding the sensitivity of ozone and OH to environmental factors. We present the results of simulations for 1998-2006 using the GEOS-Chem chemical transport model with IAV in tropical lightning constrained by satellite observations from the Lightning Imaging Sensor (LIS). We find that this imposed IAV in lightning NO x improves the ability of the model to reproduce observed IAV in tropical ozone and OH. Lightning is far more important than biomass burning in driving the IAV of tropical ozone, even though the IAV of NO x emissions from fires is greater than that from lightning. Our results indicate that the IAV in tropospheric OH is highly sensitive to lightning relative to other emissions, and suggest that lightning contributes an important fraction of the observed IAV in OH inferred from the methylchloroform proxy. Lightning affects OH through the HO 2 +NO reaction, an effect compounded by positive feedback from the resulting increase in ozone production and in CO loss. We can account in the model for the observed increase in OH in 1998-2004 and for its IAV, but the model fails to explain the OH decrease in 2004-2006. We find that stratospheric ozone plays little role in driving IAV in OH during 1998-2006, in contrast to previous studies that examined earlier periods.
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  • 20
    Publication Date: 2013-09-21
    Description: [1]  The gravity wave field in the lower stratosphere (between 15 km and 22 km altitude) above Mount Pleasant Airport (51°49’S, 58°26’W), on the Falkland Islands is studied using over 2100 high-resolution radiosonde soundings from 2002-2010. The seasonal variation in vertical direction of propagation shows a small decrease in numbers of upward propagating waves that is related to critical level filtering, however there is a very large increase in numbers of downward propagating waves between July and September; this is attributed to the proximity of the edge of the polar vortex. There is a seasonal variation in gravity wave energy density, with a large peak during the austral autumn equinox; this is markedly different to results in the literature both from Rothera, on the Antarctic Peninsula, and stations on the main Antarctic continent. This seasonal pattern has been shown to be linked to variations in the sources of upward propagating gravity waves. The seasonal variation in gravity wave characteristics above Mount Pleasant Airport seen in our results suggest that the gravity wave field in this region is determined by a combination of different gravity wave sources located above and below the lower stratosphere.
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    Topics: Geosciences , Physics
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  • 21
    Publication Date: 2013-09-21
    Description: [1]  Observed evaporative demand has decreased worldwide during the past several decades. This trend is also noted on the Tibetan Plateau, a region that is particularly sensitive to climate change. However, patterns and trends of evapotranspiration and their relationship to drought stress on the Tibetan Plateau are complex and poorly understood. Here, we analyze spatiotemporal changes in evapotranspiration and effective moisture (defined as the ratio of actual evapotranspiration ( ET a ) to reference crop evapotranspiration ( ET o )) based on the modified Lund–Potsdam–Jena Dynamic Global Vegetation Model (LPJ). Climate data from 80 meteorological stations on the Tibetan Plateau were compiled for the period 1981–2010 and future climate projections were generated by a regional climate model through the 21 st century. The results show regional trends towards decreasing ET o and statistically significant increases in ET a ( p  〈 0.05) and effective moisture during the period 1981–2010 ( p  〈 0.001). A transition from significant negative to positive ET o occurred in 1997. Additionally, a pronounced increase in effective moisture occurred during the period 1981–1997 because of significant decreased ET o before 1997. In the future, regional ET o and ET a are projected to increase, thus reducing drought stress, because of generally increased effective moisture. Future regional differences are most pronounced in terms of effective moisture, which shows notable increases in the northwestern plateau and decreases in the southeastern plateau. Moreover, the reduced magnitude of effective moisture is likely to intensify in the long term, due mainly to increased evaporative demand.
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    Topics: Geosciences , Physics
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  • 22
    Publication Date: 2013-09-21
    Description: [1]  Changes in the hydrological cycle being caused by human-induced global warming are triggering variations in observed spatiotemporal distributions of precipitation and temperature extremes, and hence in droughts and floods across China. Evaluation of future climate extremes based on General Circulation Models (GCMs) outputs will be of great importance in scientific management of water resources and agricultural activities. In this study, 5 precipitation extreme and 5 temperature extreme indices are defined. This study analyzes daily precipitation and temperature data for 1960-2005 from 529 stations in China and outputs of GCMs from the Coupled Model Intercomparison Project Phase 3 (CMIP3) and Phase 5 (CMIP5). Downscaling methods, based on QQ-plot and transfer functions, are used to downscale GCMs outputs to the site scale. Performances of GCMs in simulating climate extremes were evaluated using the Taylor diagram. Results showed that: (1) the multimodel CMIP5 ensemble performs the best in simulating observed extreme conditions; (2) precipitation processes are intensifying with increased frequency and intensity across entire China. The southwest China, however, is dominated by lengthening maximum consecutive dry days and also more heavy precipitation extremes; (3) warming processes continue with increasing warm nights, decreasing frost days and lengthening heat waves during the 21 st century; (4) changes in precipitation and temperature extremes exhibit larger changing magnitudes under RCP85 scenario; (5) for the evolution of changes in extremes, in most cases, the spatial pattern keeps the same, even though changing rates vary. In some cases, area with specific changing properties extends or shrinks gradually. The directions of trends may alter during the evolution; and (5) changes under RCP85 become more and more pronounced as time elapses. Under the peak-and-decline RCP26, changes in some cases don't decrease correspondingly during 2070-2099 even though the radiative forcing during 2070-2099 is less than during 2040-2069. The increase of radiative forcing triggers considerable regional variations in consecutive dry days, but causes only slight changes in the areal average in China. The results of this study imply higher flood risk across entire China but intensifying droughts in south China in the 21 st century, and also more heat-related losses in east coasts of China.
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  • 23
    Publication Date: 2013-09-21
    Description: [1]  Marine cloud brightening through sea spray injection has been proposed as a method of temporarily alleviating some of the impacts of anthropogenic climate change, as part of a set of technologies called geoengineering. We outline here a proposal for three coordinated climate modeling experiments to test aspects of sea spray geoengineering, to be conducted under the auspices of the Geoengineering Model Intercomparison Project (GeoMIP). The first, highly idealized, experiment ( G1ocean-albedo ) involves a uniform increase in ocean albedo to offset an instantaneous quadrupling of CO 2 concentrations from preindustrial levels. Results from a single climate model show an increased land-sea temperature contrast, Arctic warming, and large shifts in annual mean precipitation patterns. The second experiment ( G4cdnc ) involves increasing cloud droplet number concentration in all low-level marine clouds to offset some of the radiative forcing of an RCP4.5 scenario. This experiment will test the robustness of models in simulating geographically heterogeneous radiative flux changes and their effects on climate. The third experiment ( G4sea-salt ) involves injection of sea spray aerosols into the marine boundary layer between 30°S and 30°N to offset 2 W m -2 of the effective radiative forcing of an RCP4.5 scenario. A single model study shows that the induced effective radiative forcing is largely confined to the latitudes in which injection occurs. In this single model simulation, the forcing due to aerosol–radiation interactions is stronger than the forcing due to aerosol–cloud interactions.
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    Topics: Geosciences , Physics
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  • 24
    Publication Date: 2013-09-26
    Description: We have developed a new screening methodology for identifying all genes that control the expression of a target gene through genetic or metabolic interactions. The screen combines mutant libraries with luciferase reporter constructs, whose expression can be monitored in vivo and over time in different environmental conditions. We apply the method to identify the genes that control the expression of the gene acs , encoding the acetyl coenzyme A synthetase, in Escherichia coli . We confirm most of the known genetic regulators, including CRP–cAMP, IHF and components of the phosphotransferase system. In addition, we identify new regulatory interactions, many of which involve metabolic intermediates or metabolic sensing, such as the genes pgi, pfkA , sucB and lpdA , encoding enzymes in glycolysis and the TCA cycle. Some of these novel interactions were validated by quantitative reverse transcriptase-polymerase chain reaction. More generally, we observe that a large number of mutants directly or indirectly influence acs expression, an effect confirmed for a second promoter, sdhC . The method is applicable to any promoter fused to a luminescent reporter gene in combination with a deletion mutant library.
    Keywords: Genomics, Transcriptome Mapping - Monitoring Gene Expression
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  • 25
    Publication Date: 2013-09-26
    Description: Tandem repeats (TRs) are often present in proteins with crucial functions, responsible for resistance, pathogenicity and associated with infectious or neurodegenerative diseases. This motivates numerous studies of TRs and their evolution, requiring accurate multiple sequence alignment. TRs may be lost or inserted at any position of a TR region by replication slippage or recombination, but current methods assume fixed unit boundaries, and yet are of high complexity. We present a new global graph-based alignment method that does not restrict TR unit indels by unit boundaries. TR indels are modeled separately and penalized using the phylogeny-aware alignment algorithm. This ensures enhanced accuracy of reconstructed alignments, disentangling TRs and measuring indel events and rates in a biologically meaningful way. Our method detects not only duplication events but also all changes in TR regions owing to recombination, strand slippage and other events inserting or deleting TR units. We evaluate our method by simulation incorporating TR evolution, by either sampling TRs from a profile hidden Markov model or by mimicking strand slippage with duplications. The new method is illustrated on a family of type III effectors, a pathogenicity determinant in agriculturally important bacteria Ralstonia solanacearum. We show that TR indel rate variation contributes to the diversification of this protein family.
    Keywords: Computational Methods, Genomics
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  • 26
    Publication Date: 2013-09-26
    Description: A renewed interest in non-coding RNA (ncRNA) has led to the discovery of novel RNA species and post-transcriptional ribonucleoside modifications, and an emerging appreciation for the role of ncRNA in RNA epigenetics. Although much can be learned by amplification-based analysis of ncRNA sequence and quantity, there is a significant need for direct analysis of RNA, which has led to numerous methods for purification of specific ncRNA molecules. However, no single method allows purification of the full range of cellular ncRNA species. To this end, we developed a multidimensional chromatographic platform to resolve, isolate and quantify all canonical ncRNAs in a single sample of cells or tissue, as well as novel ncRNA species. The applicability of the platform is demonstrated in analyses of ncRNA from bacteria, human cells and plasmodium-infected reticulocytes, as well as a viral RNA genome. Among the many potential applications of this platform are a system-level analysis of the dozens of modified ribonucleosides in ncRNA, characterization of novel long ncRNA species, enhanced detection of rare transcript variants and analysis of viral genomes.
    Keywords: RNA characterisation and manipulation
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  • 27
    Publication Date: 2013-09-26
    Description: The synthesis of protein from messenger RNA during translation is a highly dynamic process that plays a key role in controlling the efficiency and fidelity of genome-wide protein expression. The availability of aminoacylated transfer RNA (tRNA) is a major factor influencing the speed of ribosomal movement, which depending on codon choices, varies considerably along a transcript. Furthermore, it has been shown experimentally that tRNA availability can vary significantly under different growth and stress conditions, offering the cell a way to adapt translational dynamics across the genome. Existing models of translation have neglected fluctuations of tRNA pools, instead assuming fixed tRNA availabilities over time. This has lead to an incomplete understanding of this process. Here, we show for the entire Escherichia coli genome how and to what extent translational speed profiles, which capture local aspects of translational elongation, respond to measured shifts in tRNA availability. We find that translational profiles across the genome are affected to differing degrees, with genes that are essential or related to fundamental processes such as translation, being more robust than those linked to regulation. Furthermore, we reveal how fluctuating tRNA availability influences profiles of specific sequences known to play a significant role in translational control of gene expression.
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  • 28
    Publication Date: 2013-09-26
    Description: Central to Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas systems are repeated RNA sequences that serve as Cas-protein–binding templates. Classification is based on the architectural composition of associated Cas proteins, considering repeat evolution is essential to complete the picture. We compiled the largest data set of CRISPRs to date, performed comprehensive, independent clustering analyses and identified a novel set of 40 conserved sequence families and 33 potential structure motifs for Cas-endoribonucleases with some distinct conservation patterns. Evolutionary relationships are presented as a hierarchical map of sequence and structure similarities for both a quick and detailed insight into the diversity of CRISPR-Cas systems. In a comparison with Cas-subtypes, I-C, I-E, I-F and type II were strongly coupled and the remaining type I and type III subtypes were loosely coupled to repeat and Cas1 evolution, respectively. Subtypes with a strong link to CRISPR evolution were almost exclusive to bacteria; nevertheless, we identified rare examples of potential horizontal transfer of I-C and I-E systems into archaeal organisms. Our easy-to-use web server provides an automated assignment of newly sequenced CRISPRs to our classification system and enables more informed choices on future hypotheses in CRISPR-Cas research: http://rna.informatik.uni-freiburg.de/CRISPRmap .
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  • 29
    Publication Date: 2013-09-26
    Description: Escherichia coli Exonuclease IX (ExoIX), encoded by the xni gene, was the first identified member of a novel subfamily of ubiquitous flap endonucleases (FENs), which possess only one of the two catalytic metal-binding sites characteristic of other FENs. We have solved the first structure of one of these enzymes, that of ExoIX itself, at high resolution in DNA-bound and DNA-free forms. In the enzyme–DNA cocrystal, the single catalytic site binds two magnesium ions. The structures also reveal a binding site in the C-terminal domain where a potassium ion is directly coordinated by five main chain carbonyl groups, and we show this site is essential for DNA binding. This site resembles structurally and functionally the potassium sites in the human FEN1 and exonuclease 1 enzymes. Fluorescence anisotropy measurements and the crystal structures of the ExoIX:DNA complexes show that this potassium ion interacts directly with a phosphate diester in the substrate DNA.
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  • 30
    Publication Date: 2013-09-26
    Description: One of the obstacles hindering a better understanding of cancer is its heterogeneity. However, computational approaches to model cancer heterogeneity have lagged behind. To bridge this gap, we have developed a new probabilistic approach that models individual cancer cases as mixtures of subtypes. Our approach can be seen as a meta-model that summarizes the results of a large number of alternative models. It does not assume predefined subtypes nor does it assume that such subtypes have to be sharply defined. Instead given a measure of phenotypic similarity between patients and a list of potential explanatory features, such as mutations, copy number variation, microRNA levels, etc., it explains phenotypic similarities with the help of these features. We applied our approach to Glioblastoma Multiforme (GBM). The resulting model Prob_GBM, not only correctly inferred known relationships but also identified new properties underlining phenotypic similarities. The proposed probabilistic framework can be applied to model relations between similarity of gene expression and a broad spectrum of potential genetic causes.
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  • 31
    Publication Date: 2013-09-26
    Description: Estrogen regulates over a thousand genes, with an equal number of them being induced or repressed. The distinct mechanisms underlying these dual transcriptional effects remain largely unknown. We derived comprehensive views of the transcription machineries assembled at estrogen-responsive genes through integrating multiple types of genomic data. In the absence of estrogen, the majority of genes formed higher-order chromatin structures, including DNA loops tethered to protein complexes involving RNA polymerase II (Pol II), estrogen receptor alpha (ERα) and ERα-pioneer factors. Genes to be ‘repressed’ by estrogen showed active transcription at promoters and throughout the gene bodies; genes to be ‘induced’ exhibited active transcription initiation at promoters, but with transcription paused in gene bodies. In the presence of estrogen, the majority of estrogen-induced genes retained the original higher-order chromatin structures, whereas most estrogen-repressed genes underwent a chromatin reconfiguration. For estrogen-induced genes, estrogen enhances transcription elongation, potentially through recruitment of co-activators or release of co-repressors with unique roles in elongation. For estrogen-repressed genes, estrogen treatment leads to chromatin structure reconfiguration, thereby disrupting the originally transcription-efficient chromatin structures. Our in silico studies have shown that estrogen regulates gene expression, at least in part, through modifying previously assembled higher-order complexes, rather than by facilitating de novo assembly of machineries.
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  • 32
    Publication Date: 2013-09-26
    Description: The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1–MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes.
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  • 33
    Publication Date: 2013-09-26
    Description: Selective inhibitory crosstalk has been known to occur within the signaling pathways of the dioxin (AhR) and estrogen (ERα) receptors. More specifically, ERα represses a cytochrome P450-encoding gene ( CYP1A1 ) that converts cellular estradiol into a metabolite that inhibits the cell cycle, while it has no effect on a P450-encoding gene ( CYP1B1 ) that converts estrodiol into a genotoxic product. Here we show that ERα represses CYP1A1 by targeting the Dnmt3B DNA methyltransferase and concomitant DNA methylation of the promoter. We also find that histone H2A.Z can positively contribute to CYP1A1 gene expression, and its presence at that gene is inversely correlated with DNA methylation. Taken together, our results provide a framework for how ERα can repress transcription, and how that impinges on the production of an enzyme that generates genotoxic estradiol metabolites, and potential breast cancer progression. Finally, our results reveal a new mechanism for how H2A.Z can positively influence gene expression, which is by potentially competing with DNA methylation events in breast cancer cells.
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  • 34
    Publication Date: 2013-09-26
    Description: TFIIIB and TFIIIC are multi-subunit factors required for transcription by RNA polymerase III. We present a genome-wide high-resolution footprint map of TFIIIB–TFIIIC complexes in Saccharomyces cerevisiae , obtained by paired-end sequencing of micrococcal nuclease-resistant DNA. On tRNA genes, TFIIIB and TFIIIC form stable complexes with the same distinctive occupancy pattern but in mirror image, termed ‘bootprints’. Global analysis reveals that the TFIIIB–TFIIIC transcription complex exhibits remarkable structural elasticity: tRNA genes vary significantly in length but remain protected by TFIIIC. Introns, when present, are markedly less protected. The RNA polymerase III transcription terminator is flexibly accommodated within the transcription complex and, unexpectedly, plays a major structural role by delimiting its 3'-boundary. The ETC sites, where TFIIIC binds without TFIIIB, exhibit different bootprints, suggesting that TFIIIC forms complexes involving other factors. We confirm six ETC sites and report a new site ( ETC10 ). Surprisingly, TFIIIC, but not TFIIIB, interacts with some centromeric nucleosomes, suggesting that interactions between TFIIIC and the centromere may be important in the 3D organization of the nucleus.
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  • 35
    Publication Date: 2013-09-26
    Description: The process of DNA mismatch repair is initiated when MutS recognizes mismatched DNA bases and starts the repair cascade. The Escherichia coli MutS protein exists in an equilibrium between dimers and tetramers, which has compromised biophysical analysis. To uncouple these states, we have generated stable dimers and tetramers, respectively. These proteins allowed kinetic analysis of DNA recognition and structural analysis of the full-length protein by X-ray crystallography and small angle X-ray scattering. Our structural data reveal that the tetramerization domains are flexible with respect to the body of the protein, resulting in mostly extended structures. Tetrameric MutS has a slow dissociation from DNA, which can be due to occasional bending over and binding DNA in its two binding sites. In contrast, the dimer dissociation is faster, primarily dependent on a combination of the type of mismatch and the flanking sequence. In the presence of ATP, we could distinguish two kinetic groups: DNA sequences where MutS forms sliding clamps and those where sliding clamps are not formed efficiently. Interestingly, this inability to undergo a conformational change rather than mismatch affinity is correlated with mismatch repair.
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  • 36
    Publication Date: 2013-09-26
    Description: Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the regulation of H4S47ph levels was unknown. Here, we show that three phosphatases (PP1α, PP1β and Wip1) regulate H4S47ph levels and H3.3 deposition. Depletion of each of the three phosphatases results in increased H4S47ph levels. Moreover, PP1α, PP1β and Wip1 bind H3-H4 in vitro and in vivo , whereas only PP1α and PP1β, but not Wip1, interact with Pak2 in vivo . These results suggest that PP1α, PP1β and Wip1 regulate the levels of H4S47ph through directly acting on H4S47ph, with PP1α and PP1β also likely regulating the activity of Pak2. Finally, depletion of PP1α, PP1β and Wip1 leads to increased H3.3 occupancy at candidate genes tested, elevated H3.3 deposition and enhanced association of H3.3 with its chaperones HIRA and Daxx. These results reveal a novel role of three phosphatases in chromatin dynamics in mammalian cells.
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  • 37
    Publication Date: 2013-09-26
    Description: Previously we identified Rrp1 and Rrp2 as two proteins required for the Sfr1/Swi5-dependent branch of homologous recombination (HR) in Schizosaccharomyces pombe . Here we use a yeast two-hybrid approach to demonstrate that Rrp1 and Rrp2 can interact with each other and with Swi5, an HR mediator protein. Rrp1 and Rrp2 form co-localizing methyl methanesulphonate–induced foci in nuclei, further suggesting they function as a complex. To place the Rrp1/2 proteins more accurately within HR sub-pathways, we carried out extensive epistasis analysis between mutants defining Rrp1/2, Rad51 (recombinase), Swi5 and Rad57 (HR-mediators) plus the anti-recombinogenic helicases Srs2 and Rqh1. We confirm that Rrp1 and Rrp2 act together with Srs2 and Swi5 and independently of Rad57 and show that Rqh1 also acts independently of Rrp1/2. Mutants devoid of Srs2 are characterized by elevated recombination frequency with a concomitant increase in the percentage of conversion-type recombinants. Strains devoid of Rrp1 or Rrp2 did not show a change in HR frequency, but the number of conversion-type recombinants was increased, suggesting a possible function for Rrp1/2 with Srs2 in counteracting Rad51 activity. Our data allow us to propose a model placing Rrp1 and Rrp2 functioning together with Swi5 and Srs2 in a synthesis-dependent strand annealing HR repair pathway.
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  • 38
    Publication Date: 2013-09-26
    Description: In eukaryotic cells, gene expression is mediated by enhancer activation of RNA polymerase at distant promoters. Recently, distinctions between enhancers and promoters have been blurred by the discovery that enhancers are associated with RNA polymerase and are sites of RNA synthesis. Here, we present an analysis of the insulin-like growth factor 2/H19 muscle enhancer. This enhancer includes a short conserved core element that is organized into chromatin typical of mammalian enhancers, binds tissue-specific transcription factors and functions on its own in vitro to activate promoter transcription. However, in a chromosomal context, this element is not sufficient to activate distant promoters. Instead, enhancer function also requires transcription in cis of a long non-coding RNA, Nctc1 . Thus, the insulin-like growth factor 2/H19 enhancer is an active transcriptional complex whose own transcription is essential to its function.
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  • 39
    Publication Date: 2013-09-26
    Description: Evolutionarily conserved RNA secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus RNA structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, RNAz and SISSIz, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies 〉4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5–22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved RNA structure motifs in the long noncoding RNA MALAT1 . This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes.
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  • 40
    Publication Date: 2013-09-26
    Description: The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.
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  • 41
    Publication Date: 2013-09-26
    Description: RNA-based therapeutic approaches using splice-switching oligonucleotides have been successfully applied to rescue dystrophin in Duchenne muscular dystrophy (DMD) preclinical models and are currently being evaluated in DMD patients. Although the modular structure of dystrophin protein tolerates internal deletions, many mutations that affect nondispensable domains of the protein require further strategies. Among these, trans -splicing technology is particularly attractive, as it allows the replacement of any mutated exon by its normal version as well as introducing missing exons or correcting duplication mutations. We have applied such a strategy in vitro by using cotransfection of pre– trans -splicing molecule (PTM) constructs along with a reporter minigene containing part of the dystrophin gene harboring the stop-codon mutation found in the mdx mouse model of DMD. Optimization of the different functional domains of the PTMs allowed achieving accurate and efficient trans -splicing of up to 30% of the transcript encoded by the cotransfected minigene. Optimized parameters included mRNA stabilization, choice of splice site sequence, inclusion of exon splice enhancers and artificial intronic sequence. Intramuscular delivery of adeno-associated virus vectors expressing PTMs allowed detectable levels of dystrophin in mdx and mdx4Cv , illustrating that a given PTM can be suitable for a variety of mutations.
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  • 42
    Publication Date: 2013-10-01
    Description: [1]  The problem of diurnal variation in surface emissivity over the Sahara Desert during non-raining days is studied and assessed with observations from the Infrared Atmospheric Sounding Interferometer (IASI). The analysis has been performed over a Sahara Desert dune target area during July 2010. Spinning Enhanced Visible and Infrared Imager observations from the European geostationary platform Meteosat-9 (Meteorological Satellite 9) have been also used to characterize the target area. Although the amplitude of this daily cycle has been shown to be very small, we argue that suitable nighttime meteorological conditions and the strong contrast of the reststrahlen absorption bands of quartz (8–14 μ m) can amplify its effect over the surface spectral emissivity. The retrieval of atmospheric parameters show that at nighttime an atmospheric temperature inversion occurs close to the surface yielding a thin boundary layer which acts like a lid, keeping normal convective overturning of the atmosphere from penetrating through the inversion. This mechanism traps water vapour close to the land and drives the direct adsorption of water vapour at the surface during the night. The diurnal variation in emissivity at 8.7 μ m has been found to be as large as 0.03 with high values at night and low values during the day. At 10.8 μ m and 12 μ m the variation has the same sign as that at 8.7 μ m, but with a smaller amplitude, 0.019 and 0.014, respectively. The impact of these diurnal variations on the retrieval of surface temperature and atmospheric parameters has been analyzed.
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    Topics: Geosciences , Physics
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  • 43
    Publication Date: 2013-10-01
    Description: [1]  Retrieval of aerosol optical depth (AOD) from the Moderate Resolution Imaging Spectroradiometer (MODIS) using the Collection 5 (C005) algorithm provides large-scale (10x10 km) estimates that can be used to predict surface layer concentrations of particulate matter with aerodynamic diameter smaller than 2.5 microns (PM 2.5 ). However, these large-scale estimates are not suitable for identifying intra-urban variability of surface PM 2.5 concentrations during wildfire events when individual plumes impact populated areas. We demonstrate a method for providing high-resolution (2.5 km) kernel-smoothed estimates of AOD over California during the 2008 northern California fires. The method uses high-resolution surface reflectance ratios of the 0.66 µm and 2.12 µm channels, a locally derived aerosol optical model characteristic of fresh wildfire plumes, and a relaxed cloud filter. Results show that the AOD derived for the 2008 northern California fires outperformed the standard product in matching observed aerosol optical thickness (AOT) at three coastal AERONET sites and routinely explained more than 50% of the variance in hourly surface PM 2.5 concentrations observed during the wildfires.
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  • 44
    Publication Date: 2013-10-05
    Description: [1]  An observational study of nonlinear interaction between the quasi two-day wave (QTDW) and the diurnal and semidiurnal tides from meteor radar measurements at Maui is reported. The diurnal and semidiurnal tides show a short-term variation with the QTDW activity. The variation of amplitude of the semidiurnal tide is opposite to that of the QTDW. The minimum amplitudes of the diurnal tide appear several days later than the maximum amplitudes of the QTDW, and the diurnal tide obviously strengthens when the QTDW drops to small amplitudes. The bispectrum analysis shows significant nonlinear interactions among the QDTW and the tidal components. The two quasi 16-h modes with periods of 16.2 h and 15.8 h generated in the interactions of the QTDW with the diurnal and semidiurnal tides can clearly be distinguished because of the slight deviation of the QTDW period from 48 h. The bicoherence spectrum demonstrates that the QTDW and the semidiurnal tide have quite strong levels of coherence, indicating that the nonlinear interaction is a mechanism responsible for the variability of the semidiurnal tide. Although there is also some interaction between the QTDW and the diurnal tide, their coherence level is low. When the QTDW drops to very weak amplitudes, the background wind decreases and reverses. During this time, the diurnal tide holds large amplitudes. These results support the notion that the variability of the diurnal tide is mainly attributable to the strong QTDW-induced changes in the background atmosphere, which was shown in the modeling study by Chang et al . [2011]. Hence, both the nonlinear interaction and the background flow changes are responsible for the observed variation of the diurnal tide.
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  • 45
    Publication Date: 2013-10-05
    Description: [1]  We conducted three-member ensemble simulations using a global atmospheric model with a high-horizontal resolution of a 60-km grid size for the period 1872-2099 (228 years). Between 1872 and 2005, the model was forced with observed historical sea surface temperatures (SST), while between 2006 and 2099 the boundary SST data were estimated using the multi-model ensemble (MME) of the Coupled Model Intercomparison Project phase 3 (CMIP3) models and assuming A1B emission scenario. Annual mean precipitation (PAVE), the Simple Daily Precipitation Intensity Index (SDII), and the maximum 5-day precipitation total (R5d) averaged over East Asia increase almost monotonically through the 21st century. The statistically significant area of precipitation intensity increase is larger for 2080-2099 than for 2046-2065. In particular, intense rainfall will increase over northern and southern China during 2080-2099. The conversion rate from water vapor to precipitation per 1 °C rise in surface air temperature for SDII and R5D is much larger than that for PAVE during the 21st century. This suggests that extreme rainfall events will occur more frequently than moderate rainfall events even if the amount of temperature rise is same. Future changes in the horizontal transport of water vapor also leads to more intense precipitation over East Asia. In particular, the increase in clockwise water vapor transport due to intensification of the subtropical high contributes to increased intense precipitation over southern China.
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  • 46
    Publication Date: 2013-10-05
    Description: [1]  An aircraft field study [POST; Physics Of Stratocumulus Top] was conducted off the central California Coast in July and August of 2008 to deal with the known difficulty of measuring entrainment rates in the radiatively important stratocumulus [Sc] prevalent in that area. The CIRPAS Twin Otter research aircraft flew 15 quasi-Lagrangian flights in unbroken Sc and carried a full complement of probes including three high data-rate probes UFT-M [Ultra-Fast Temperature probe], PVM [Particulate Volume Monitor] probe, and gust probe. The probes’ co-location near the nose of the Twin Otter permitted estimation of entrainment fluxes and rates with an incloud resolution of 1 m. [2]  Results include the following: Application of the conditional-sampling variation of classical mixed layer theory for calculating the entrainment rate into cloud top for POST flights is shown to be inadequate for most of the Sc. Estimated rates resemble previous results after theory is modified to take into account both entrainment and evaporation at cloud top given the strong wind shear and mixing at cloud top. Entrainment rates show a tendency to decrease for large shear values, and the largest rates are for the smallest temperature jumps across the inversion. Measurements indirectly suggest that entrained parcels are primarily cooled by infrared flux divergence rather than cooling from droplet evaporation, while detrainment at cloud top causes droplet evaporation and cooling in the EIL [Entrainment Interface Layer] above cloud top.
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  • 47
    Publication Date: 2013-09-10
    Description: [1]  We present new measurements of the time-dependence of the ice nucleating ability of a wide range of materials including the minerals montmorillonite and kaolinite, the biological proxy ice nuclei Icemax, and flame soot generated from the incomplete combustion of ethylene gas. We also present time-dependence for ambient ice nuclei collected from rain water samples. Our data show that the time-dependence for all materials studied here is weak, suggesting that the modified singular approximation is valid over the range of times and temperatures encountered for mixed-phase clouds.
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  • 48
    Publication Date: 2013-09-10
    Description: [1]  Attributing changes in extreme daily precipitation to global warming is difficult, even when based on global climate model simulations or statistical trend analyses. The question about trends in extreme precipitation and their causes has been elusive because of climate models’ limited precision and the fact that extremes are both rare and occur at irregular intervals. Here a newly discovered empirical relationship between the wet-day mean and percentiles in 24-hr precipitation amounts was used to show that trends in the wet-day 95th percentiles world-wide have been influenced by the global mean temperature, consistent with an accelerated hydrological cycle caused by a global warming. A multiple regression analysis was used as a basis for an attribution analysis by matching temporal variability in precipitation statistics with the global mean temperature.
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  • 49
    Publication Date: 2013-09-11
    Description: [1]  We implement a new isoprene oxidation mechanism in a global 3-D chemical transport model (GEOS-Chem). Model results are evaluated with observations for ozone, isoprene oxidation products, and related species from the ICARTT aircraft campaign over the eastern United States in summer 2004. The model achieves an unbiased simulation of ozone in the boundary layer and the free troposphere, reflecting canceling effects from recent model updates for isoprene chemistry, bromine chemistry, and HO 2 loss to aerosols. Simulation of the ozone-CO correlation is improved relative to previous versions of the model and this is attributed to a lower and reversible yield of isoprene nitrates, increasing the ozone production efficiency (OPE) per unit of nitrogen oxides (NO x  ≡ NO + NO 2 ). The model successfully reproduces the observed concentrations of organic nitrates (∑ANs) and their correlations with HCHO and ozone. ∑ANs in the model is principally composed of secondary isoprene nitrates, including a major contribution from nighttime isoprene oxidation. The correlations of ∑ANs with HCHO and ozone then provide sensitive tests of isoprene chemistry and argue in particular against a fast isomerization channel for isoprene peroxy radicals. ∑ANs can provide an important reservoir for exporting NO x from the US boundary layer. We find that the dependence of surface ozone on isoprene emission is positive throughout the US, even if NO x emissions are reduced by a factor of 4. Previous models showed negative dependences that we attribute to erroneous titration of OH by isoprene.
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  • 50
    Publication Date: 2013-09-13
    Description: [1]  The extent to which the rain rate from shallow, liquid-phase clouds is microphysically influenced by aerosol, and therefore drop concentration N d perturbations, is addressed through analysis of the precipitation susceptibility, S o . Previously published work, based on both models and observations, disagrees on the qualitative behavior of S o with respect to variables such as liquid water path L or the ratio between accretion and autoconversion rates. Two primary responses have emerged: (i) S o decreases monotonically with increasing L and (ii) S o increases with L , reaches a maximum, and decreases thereafter. Here we use a variety of modeling frameworks ranging from box models of (size-resolved) collision-coalescence, to trajectory ensembles based on large eddy simulation to explore the role of time available for collision-coalescence t c in determining the S o response. The analysis shows that an increase in t c shifts the balance of rain production from autoconversion (a N d -dependent process) to accretion (roughly independent of N d ), all else (e.g., L ) equal. Thus with increasing cloud contact time warm rain production becomes progressively less sensitive to aerosol, all else equal. When the time available for collision-coalescence is a limiting factor, S o increases with increasing L whereas when there is ample time available, S o decreases with increasing L . The analysis therefore explains the differences between extant studies in terms of an important precipitation-controlling parameter, namely the integrated liquid water history over the course of an air parcel's contact with a cloud.
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  • 51
    Publication Date: 2013-09-13
    Description: [1]  In previous studies, the Yonsei University (YSU) planetary boundary layer (PBL) scheme implemented in the Weather Research and Forecasting (WRF) model was reported to perform less well at night, while performing better during the day. Compared to observations, predicted nocturnal low-level jets (LLJs) were typically weaker and higher. Also, the WRF model with Chemistry (WRF/Chem) with the YSU scheme was reported to sometimes overestimate near-surface ozone (O 3 ) concentration during the nighttime. The updates incorporated in WRF version 3.4.1, include modifications of the nighttime velocity scale used in the YSU boundary-layer scheme. The impacts of this update on the prediction of nighttime boundary layers and related implications for wind resource assessment and air quality simulations are examined in this study. The WRF/Chem model with the updated YSU scheme predicts smaller eddy diffusivities in the nighttime boundary layer, and consequently lower and stronger LLJs over a domain focusing on the southern Great Plains area, showing a better agreement with the observations. As a result, related overestimation problems for near-surface temperature and wind speeds appear to be resolved, and the nighttime minimum near-surface O 3 concentrations are better captured. Simulated vertical distributions of meteorological and chemical variables for weak wind regimes (e.g., in the absence of LLJ) are less impacted by the YSU updates.
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  • 52
    Publication Date: 2013-09-13
    Description: [1]  We introduce novel methodology to examine the ability of six regional climate models (RCMs) in the North American Regional Climate Change Assessment Program (NARCCAP) ensemble to simulate past extreme precipitation events seen in the observational record over two different regions and seasons. [2]  Our primary objective is to examine the strength of daily correspondence of extreme precipitation events between observations and the output of both the RCMs and the driving reanalysis product. To explore this correspondence, we employ methods from multivariate extreme value theory. These methods require that we account for marginal behavior, and we first model and compare climatological quantities which describe tail behavior of daily precipitation for both the observations and model output before turning attention to quantifying the correspondence of the extreme events. Daily precipitation in a west coast region of North America is analyzed in two seasons, and it is found that the simulated extreme events from the reanalysis-driven NARCCAP models exhibit strong daily correspondence to extreme events in the observational record. Precipitation over a central region of the United States is examined, and we find some daily correspondence between winter extremes simulated by reanalysis-driven NARCCAP models and those seen in observations, but no such correspondence is found forsummer extremes. Furthermore, we find greater discrepancies among the NARCCAP models in the tail characteristics of the distribution of daily summer precipitation over this region than seen in precipitation over the west coast region. We find that the models which employ spectral nudging exhibit stronger tail dependence to observations in the central region.
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  • 53
    Publication Date: 2013-09-14
    Description: [1]  Atmospheric organic aerosol concentrations depend in part on the gas-particle partitioning of primary organic aerosol (POA) emissions. Consequently, heating and dilution were used to investigate the volatility of biomass burning smoke particles from combustion of common North American trees/shrubs/grasses during the third Fire Lab at Missoula Experiment (FLAME-III). Fifty to eighty percent of the mass of biomass burning POA evaporated when isothermally diluted from plume (~1000 µg m -3 ) to ambient-like concentrations (~10 µg m -3 ), while roughly eighty percent of the POA evaporated upon heating to 100 °C in a thermodenuder with a residence time of ~14 seconds. Therefore, the majority of the POA emissions were semi-volatile. Thermodenuder measurements performed at three different residence times indicated that there were not substantial mass transfer limitations to evaporation (i.e., the mass accommodation coefficient appears to be between 0.1 and 1). An evaporation kinetics model was used to derive volatility distributions and enthalpies of vaporization from the thermodenuder data. A single volatility distribution can be used to represent the measured gas-particle partitioning from the entire set of experiments, including different fuels, organic aerosol concentrations, and thermodenuder residence times. This distribution, derived from the thermodenuder measurements, also predicts the dilution-driven changes in gas-particle partitioning. This volatility distribution and associated emission factors for each fuel studied can be used to update emission inventories and to simulate the gas-particle partitioning of biomass burning POA emissions in chemical transport models.
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  • 54
    Publication Date: 2013-09-14
    Description: [1]  We investigate the variations in tropospheric circulation over Asia associated with the stratospheric quasi-biennial oscillation (QBO) during Northern Hemisphere (NH) autumn (September-November) using the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) Reanalysis and NCEP-Department of Energy (DOE) Reanalysis II data sets for a 25-year period (1980-2004). The anomaly fields in this study are expressed as the easterly years minus the westerly years of the QBO. The zonal wind distribution at 200 hPa indicates easterly anomalies at low latitudes from India through Taiwan, statistically significant westerly anomalies at mid-latitudes including the Tibetan Plateau to northern China, and significant easterly anomalies in the high-latitude Eurasia north of 50°N. A momentum balance analysis indicates that these anomalies over Asia are attributable to atmospheric waves and residual mean meridional flow. Significant northward and descending anomalies are observed in the lower stratosphere over Asia, with detectable signals in the troposphere around Tibet. The adiabatic heating due to descending motions in the region centering on India and Bangladesh is consistent with the distribution of rainfall anomalies. The formation of zonal wind anomalies over South Asia seems to be associated with not only wave activities but also adiabatic heating and thermal advection. We suggest that the QBO may be linked to tropospheric circulation over Asia through wave activities and convective activities in autumn, and the wave activities in the low latitudes associated with the QBO seem to be connected with the rainfall distribution over the Asian monsoon region.
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  • 55
    Publication Date: 2013-09-16
    Description: [1]  Subtropical cyclogenesis and tropical transitions (TT) over the South Atlantic Ocean only received attention after the first documented Hurricane Catarina occurred close to the Southern Brazilian coast in March 2004. However, due to the lack of studies in this part of Atlantic Ocean, it is still unclear what the main environmental conditions and dynamical processes associated with TT or even subtropical cyclogenesis are over the region. This study presents a synoptic and dynamical analysis of the Subtropical Cyclone Anita which occurred in March 2010 near Brazilian coast. This system started as a pure subtropical cyclone, evolved to a condition favorable to TT, later developed a cold-cored structure and decayed as an extratropical cyclone. During the period favorable for TT, the turbulent heat fluxes (latent plus sensible) from the ocean decreased and Anita started interacting with another extratropical disturbance preventing the TT to happen. This interaction, in turn, increased the vertical wind shear, let the extratropical transition to occur and promoted the westward displacement of Anita to colder waters thus decreasing the turbulent heat fluxes. The results suggest that the combination of a dipole blocking pattern aloft, with contribution from barotropic energy conversions, and strong turbulent fluxes are important ingredients for tropical storms development. Hybrid storms in such environmental conditions can be one form of precursors of hurricanes over the South Atlantic.
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  • 56
    Publication Date: 2013-09-20
    Description: [1]  The Suomi National Polar-orbiting Partnership (NPP) satellite was launched on October 28, 2011 and carries the Advanced Technology Microwave Sounder (ATMS) on board. ATMS is a cross-track scanning instrument observing in 22 channels at frequencies ranging from 23 to 183 GHz, permitting the measurements of the atmospheric temperature and moisture under most weather conditions. In this study, the ATMS radiometric calibration algorithm used in the operational system is first evaluated through independent analyses of prelaunch thermal vacuum data. It is found that the ATMS peak nonlinearity for all the channels are less than 0.5 K, which is well within the specification. For the characterization of the ATMS instrument sensitivity or noise equivalent differential temperatures (NEDT), both standard deviation and Allan variance of warm counts are computed and compared. It is shown that NEDT derived from the standard deviation is about three to five times larger than that from the Allan variance. It is shown that this difference results from a non-stationary component in the standard deviation of warm counts. The Allan variance is better suited than the standard deviation for describing NEDT. In the ATMS sensor brightness temperature data record (SDR) processing algorithm, the antenna gain efficiencies of main beam, cross-polarization beam and side lobes must be derived accurately from the antenna gain distribution function. However, uncertainties remain in computing the efficiencies at ATMS high frequencies. Thus, ATMS antenna brightness temperature data records (TDR) at channels 1 to 15 are converted to SDR with the actual beam efficiencies whereas those for channels 16 to 22 are only corrected for the near-field side-lobe contributions. The biases of ATMS SDR measurements to the simulations are consistent between GPS RO and NWP data and are generally less than 0.5 K for those temperature sounding channels where both the forward model and input atmospheric profiles are reliable.
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  • 57
    Publication Date: 2013-09-20
    Description: [1]  The operational ALADIN-France 3D-Var system is based on static background error covariances calculated off-line during a few-week past period. In this study, the impact of an on-line updated specification of background error covariances is evaluated in the ALADIN-France system. This evaluation is done by comparing three experiments, respectively based on (i) covariances calculated from a monthly average over a past period, (ii) covariances calculated from a monthly average over the period of study, and (iii) covariances calculated from a sliding daily average over the period of study. Firstly, it is shown through a comparison between experiments (i) and (ii) that updating the monthly average of error covariances has a positive impact on the short-range forecast quality. This is related to the specification of covariances which are more representative of average weather regimes at play during the period of study. Secondly, a comparison between experiments (ii) and (iii) indicates that additional positive impacts of a daily update of error covariances are also visible, although they tend to be somewhat localized and modest during this period. These impacts are illustrated by case studies for humidity during an anticyclonic situation, and for wind during a cyclonic event. These results support the idea to consider an on-line updated specification of background error covariances.
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  • 58
    Publication Date: 2013-09-22
    Description: [1]  On 5 August 2008, a localized heavy rainfall event caused a rapid increase in drainpipe discharge, which killed five people working in a drainpipe near Zoshigaya, Tokyo. This study compared the effects of artificial land cover and anthropogenic heat on this localized heavy rainfall event based on three ensemble experiments using a cloud-resolving model that includes realistic urban features. The first experiment (CTRL) considered realistic land cover and urban features, including artificial land cover, anthropogenic heat, and urban geometry. In the second experiment (NOAH), anthropogenic heat was ignored. In the third experiment (NOLC), urban heating from artificial land cover was reduced by keeping the urban geometry but with roofs, walls, and roads of artificial land cover replaced by shallow water. The results indicated that both anthropogenic heat and artificial land cover increased the amount of precipitation and that the effect of artificial land cover was larger than that of anthropogenic heat. However, in the middle stage of the precipitation event, the difference between the two effects became small. Weak surface heating in NOAH and NOLC reduced the near-surface air temperature and weakened the convergence of horizontal wind and updraft over the urban areas, resulting in a reduced rainfall amount compared with that in CTRL.
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  • 59
    Publication Date: 2013-09-22
    Description: [1]  Extratropical cyclones and their associated frontal systems are well known to be related to heavy precipitation events. Here an objective method is used to directly link extreme precipitation events with atmospheric fronts, identified using ECMWF Interim Reanalysis data, to quantify the importance of fronts for precipitation extremes globally. In some parts of the major midlatitude storm track regions, over 90% of precipitation extremes are associated with fronts, with slightly more events associated with warm fronts than cold fronts. On average 51% of global precipitation extremes are associated with fronts, with 75% in the midlatitudes and 31% in the tropics. A large proportion of extreme precipitation events occur in the presence of both a cyclone and a front, but remote fronts are responsible for many of the “front-only” events. The fronts producing extreme precipitation events are found to have up to 35% stronger frontal gradients than other fronts, potentially providing some improved forecasting capabilities for extreme precipitation events.
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  • 60
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    Oxford University Press
    Publication Date: 2013-09-26
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  • 61
    Publication Date: 2013-09-26
    Description: In reverse genetics, a gene’s function is elucidated through targeted modifications in the coding region or associated DNA cis -regulatory elements. To this purpose, recently developed customizable transcription activator-like effector nucleases (TALENs) have proven an invaluable tool, allowing introduction of double-strand breaks at predetermined sites in the genome. Here we describe a practical and efficient method for the targeted genome engineering in Drosophila . We demonstrate TALEN-mediated targeted gene integration and efficient identification of mutant flies using a traceable marker phenotype. Furthermore, we developed an easy TALEN assembly (easyT) method relying on simultaneous reactions of DNA Bae I digestion and ligation, enabling construction of complete TALENs from a monomer unit library in a single day. Taken together, our strategy with easyT and TALEN-plasmid microinjection simplifies mutant generation and enables isolation of desired mutant fly lines in the F 1 generation.
    Keywords: Synthetic Biology and Assembly Cloning
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  • 62
    Publication Date: 2013-09-26
    Description: High-throughput sequencing technologies have allowed for the cataloguing of variation in personal human genomes. In this manuscript, we present alu-detect , a tool that combines read-pair and split-read information to detect novel Alus and their precise breakpoints directly from either whole-genome or whole-exome sequencing data while also identifying insertions directly in the vicinity of existing Alus. To set the parameters of our method, we use simulation of a faux reference, which allows us to compute the precision and recall of various parameter settings using real sequencing data. Applying our method to 100 bp paired Illumina data from seven individuals, including two trios, we detected on average 1519 novel Alus per sample. Based on the faux-reference simulation, we estimate that our method has 97% precision and 85% recall. We identify 808 novel Alus not previously described in other studies. We also demonstrate the use of alu-detect to study the local sequence and global location preferences for novel Alu insertions.
    Keywords: Polymorphism/mutation detection, Genomics
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  • 63
    Publication Date: 2013-09-26
    Description: DT40 cells derived from chicken B lymphocytes exhibit exceptionally high homologous recombination rates. Therefore, they can be used as a convenient tool and model for gene targeting experiments. However, lack of efficient cloning strategies, protein purification protocols and a well annotated protein database limits the utility of these cells for proteomic studies. Here we describe a fast and inexpensive experimental pipeline for protein localization, quantification and mass spectrometry–based interaction studies using DT40 cells. Our newly designed set of pQuant vectors and a sequence- and ligation-independent cloning (SLIC) strategy allow for simple and efficient generation of gene targeting constructs, facilitating homologous-recombination–based protein tagging on a multi-gene scale. We also report proof of principle results using the key proteins involved in RNA decay, namely EXOSC8, EXOSC9, CNOT7 and UPF1.
    Keywords: Synthetic Biology and Assembly Cloning, Protein-protein interaction, Recombinant DNA expression, Recombination
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  • 64
    Publication Date: 2013-09-26
    Description: Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein–protein binding experiments revealed that 〉65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action.
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  • 65
    Publication Date: 2013-09-26
    Description: HU is a protein that plays a role in various bacterial processes including compaction, transcription and replication of the genome. Here, we use atomic force microscopy to study the effect of HU on the stiffness and supercoiling of double-stranded DNA. First, we measured the persistence length, height profile, contour length and bending angle distribution of the DNA–HU complex after different incubation times of HU with linear DNA. We found that the persistence and contour length depend on the incubation time. At high concentrations of HU, DNA molecules first become stiff with a larger value of the persistence length. The persistence length then decreases over time and the molecules regain the flexibility of bare DNA after ~2 h. Concurrently, the contour length shows a slight increase. Second, we measured the change in topology of closed circular relaxed DNA following binding of HU. Here, we observed that HU induces supercoiling over a similar time span as the measured change in persistence length. Our observations can be rationalized in terms of the formation of a nucleoprotein filament followed by a structural rearrangement of the bound HU on DNA. The rearrangement results in a change in topology, an increase in bending flexibility and an increase in contour length through a decrease in helical pitch of the duplex.
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  • 66
    Publication Date: 2013-09-26
    Description: Magnetic isotope and magnetic field effects on the rate of DNA synthesis catalysed by polymerases β with isotopic ions 24 Mg 2+ , 25 Mg 2+ and 26 Mg 2+ in the catalytic sites were detected. No difference in enzymatic activity was found between polymerases β carrying 24 Mg 2+ and 26 Mg 2+ ions with spinless, non-magnetic nuclei 24 Mg and 26 Mg. However, 25 Mg 2+ ions with magnetic nucleus 25 Mg were shown to suppress enzymatic activity by two to three times with respect to the enzymatic activity of polymerases β with 24 Mg 2+ and 26 Mg 2+ ions. Such an isotopic dependence directly indicates that in the DNA synthesis magnetic mass-independent isotope effect functions. Similar effect is exhibited by polymerases β with Zn 2+ ions carrying magnetic 67 Zn and non-magnetic 64 Zn nuclei, respectively. A new, ion–radical mechanism of the DNA synthesis is suggested to explain these effects. Magnetic field dependence of the magnesium-catalysed DNA synthesis is in a perfect agreement with the proposed ion–radical mechanism. It is pointed out that the magnetic isotope and magnetic field effects may be used for medicinal purposes (trans-cranial magnetic treatment of cognitive deceases, cell proliferation, control of the cancer cells, etc).
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  • 67
    Publication Date: 2013-09-26
    Description: Translation of the sigma factor RpoS is activated by DsrA, RprA and ArcA, three small non-coding sRNAs (sRNA) that expose the ribosome-binding site (RBS) by opening up an inhibitory loop. In the RpoS network, no sRNAs have been found to pair with the RBS, a most common sRNA target site in bacteria. Here, we generate Ribo-0, an artificial sRNA, which represses rpoS translation by pairing with the RBS. Ribo-0 bypasses the RNA chaperon Hfq but requires the RBS to be loosely blocked. Ribo-0 interacts with DsrA and reshapes the RpoS network. Specifically, in the intact RpoS network, DsrA activates rpoS translation by freeing up the RBS. In the modified RpoS network where Ribo-0 is introduced, the DsrA-caused RBS exposure facilitates Ribo-0 binding, thereby strengthening Ribo-0 inhibition. In other words, Ribo-0 changes DsrA from an activator to an accomplice for repressing rpoS translation. This work presents an artificial mechanism of rpoS regulation, reveals mutual effects of native and synthetic players and demonstrates genetic context-dependency of their functions.
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  • 68
    Publication Date: 2013-09-26
    Description: Revealing the clonal composition of a single tumor is essential for identifying cell subpopulations with metastatic potential in primary tumors or with resistance to therapies in metastatic tumors. Sequencing technologies provide only an overview of the aggregate of numerous cells. Computational approaches to de-mix a collective signal composed of the aberrations of a mixed cell population of a tumor sample into its individual components are not available. We propose an evolutionary framework for deconvolving data from a single genome-wide experiment to infer the composition, abundance and evolutionary paths of the underlying cell subpopulations of a tumor. We have developed an algorithm (TrAp) for solving this mixture problem. In silico analyses show that TrAp correctly deconvolves mixed subpopulations when the number of subpopulations and the measurement errors are moderate. We demonstrate the applicability of the method using tumor karyotypes and somatic hypermutation data sets. We applied TrAp to Exome-Seq experiment of a renal cell carcinoma tumor sample and compared the mutational profile of the inferred subpopulations to the mutational profiles of single cells of the same tumor. Finally, we deconvolve sequencing data from eight acute myeloid leukemia patients and three distinct metastases of one melanoma patient to exhibit the evolutionary relationships of their subpopulations.
    Keywords: Computational Methods
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  • 69
    Publication Date: 2013-09-26
    Description: The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons but also regulates the abundance of cellular RNAs. We sought to identify transcripts that are regulated by two novel NMD factors, DHX34 and neuroblastoma amplified sequence (NBAS), which were identified in a genome-wide RNA interference screen in Caenorhabditis elegans and later shown to mediate NMD in vertebrates. We performed microarray expression profile analysis in human cells, zebrafish embryos and C. elegans that were individually depleted of these factors. Our analysis revealed that a significant proportion of genes are co-regulated by DHX34, NBAS and core NMD factors in these three organisms. Further analysis indicates that NMD modulates cellular stress response pathways and membrane trafficking across species . Interestingly, transcripts encoding different NMD factors were sensitive to DHX34 and NBAS depletion, suggesting that these factors participate in a conserved NMD negative feedback regulatory loop, as was recently described for core NMD factors. In summary, we find that DHX34 and NBAS act in concert with core NMD factors to co-regulate a large number of endogenous RNA targets. Furthermore, the conservation of a mechanism to tightly control NMD homeostasis across different species highlights the importance of the NMD response in the control of gene expression.
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  • 70
    Publication Date: 2013-09-26
    Description: Artificial DNA looping peptides were engineered to study the roles of protein and DNA flexibility in controlling the geometry and stability of protein-mediated DNA loops. These LZD (leucine zipper dual-binding) peptides were derived by fusing a second, C-terminal, DNA-binding region onto the GCN4 bZip peptide. Two variants with different coiled-coil lengths were designed to control the relative orientations of DNA bound at each end. Electrophoretic mobility shift assays verified formation of a sandwich complex containing two DNAs and one peptide. Ring closure experiments demonstrated that looping requires a DNA-binding site separation of 310 bp, much longer than the length needed for natural loops. Systematic variation of binding site separation over a series of 10 constructs that cyclize to form 862-bp minicircles yielded positive and negative topoisomers because of two possible writhed geometries. Periodic variation in topoisomer abundance could be modeled using canonical DNA persistence length and torsional modulus values. The results confirm that the LZD peptides are stiffer than natural DNA looping proteins, and they suggest that formation of short DNA loops requires protein flexibility, not unusual DNA bendability. Small, stable, tunable looping peptides may be useful as synthetic transcriptional regulators or components of protein–DNA nanostructures.
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  • 71
    Publication Date: 2013-10-04
    Description: [1]  The initial breakdown stage of 10 intracloud lightning flashes that may have produced terrestrial gamma-ray flashes (TGFs) are studied with wideband E-change, multi-band B-change, and VHF lightning mapping data; these flashes fit published criteria known to be associated with TGFs. The (x, y, z, t) locations of fast initial breakdown pulses (IBPs) were determined with E-change data using a time-of-arrival (TOA) technique. Each IBP includes one or more fast-rising sub-pulses. Previous research has shown that a typical intracloud flash initiates just above the main negative cloud charge (MNCC), then an initial negative leader propagates upward in 1 – 20 ms to the bottom of the upper positive cloud charge (UPCC), thereby establishing a conducting path between the MNCC and UPCC. TOA locations indicate that IBPs are directly related to the initial negative leader. The IBPs primarily occur in short (〈 750 µs) bursts of 2 – 5 pulses, and each burst produces a slow, monotonic E-change. Typically 1 – 3 IBP bursts are needed to span the vertical gap from the MNCC to the UPCC, with successive bursts separated by 1 – 5 ms. In the B-change data each IBP burst has an associated ULF pulse and several LF pulses, and these are caused by the same physical events that produce the slow, monotonic E-change and fast-rising IBP sub-pulses, respectively. Based on similarities with known TGF-associated signals, we speculate that a relativistic electron avalanche causes each LF pulse/IBP sub-pulse pair; thus each pair has the potential to cause a TGF.
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  • 72
    Publication Date: 2013-10-04
    Description: [1]  Stratospheric Sudden Warming (SSW) events are typically, but not always, accompanied by negative Northern Annular Mode anomalies in the troposphere. However, large uncertainties remain as to which dynamical processes are responsible for those anomalies.In order to highlight sources of variability in stratosphere-troposphere coupling amongst SSW events, we present a case study of three selected events and show detailed Transformed Eulerian Mean diagnostics for momentum changes in the stratosphere and troposphere in the course of those events. Our results suggest that planetary-scale waves, especially the zonal wavenumber two component, may not only play an important role for the onset of tropospheric anomalies in response to SSW events, but also for introducing variability in the vertical coupling, i.e., whether the tropospheric circulation anomalies lag, lead or occur simultaneous to the weakening of the vortex. Particularly, the meridional propagation of those waves in the upper troposphere could be an important factor that determines whether SSW events lag or lead tropospheric anomalies.
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  • 73
    Publication Date: 2013-10-04
    Description: [1]  Three years of gravity wave observations from the HIRDLS instrument on NASA's Aura satellite are examined. We produce estimates of the global distribution of gravity wave momentum flux as a function of individual observed wave packets. The observed distribution at the 25 km altitude level is dominated by the small proportion of wave packets with momentum fluxes greater than ~0.5 mPa. Depending on latitude and season, these wave packets only comprise ~7–25% of observations, but are shown to be almost entirely responsible for the morphology of the observed global momentum flux distribution. Large-amplitude wave packets are found to be more important over orographic regions than over flat ocean regions, and to be especially high in regions poleward of 40S during austral winter. The momentum flux carried by the largest packets relative to the distribution mean is observed to decrease with height over orographic wave generation regions, but to increase with height at tropical latitudes; the mesospheric intermittency resulting is broadly equivalent in both cases. Consistent with previous studies, waves in the top 10% of the extratropical distribution are observed to carry momentum fluxes more than twice the mean and waves in the top 1% more than 10× the mean, and the Gini coefficient is found to characterise the observed distributions well. These results have significant implications for gravity wave modelling.
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  • 74
    Publication Date: 2013-10-04
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  • 75
    Publication Date: 2013-10-04
    Description: [1]  Aerosol optical properties simulated by the global 3-D tropospheric chemistry and transport model GEOS-Chem (GC) from 2008 to 2010 over the contiguous United States were evaluated with ground observations from Aerosol Robotic Network (AERONET) sites and aerosol products reported by the Multi-angle Imaging SpectroRadiometer (MISR). Overall, the correlation coefficient (r) and regression slope between AERONET and GC 2° x 2.5° (2 ° latitude x 2.5 ° longitude) daily total column aerosol optical depth (AOD) was 0.6 and 0.51, respectively. After using the nested GC 0.5° x 0.667° model to control for spatial variability, removing several outliers, and averaging over a monthly timescale, the agreement was significantly improved to an r of 0.84 and a slope of 0.75. Seasonal, hourly, and geographical statistics for GC 0.5° x 0.667° and AERONET AODs show a similar data range and variation, with higher mean values in the summer, the evening, and in the eastern U.S. Smaller correlation coefficients are seen in the summer and winter, in the evening, and in the western U.S. To investigate the optical properties of major GC tracers, MISR Level 2 aerosol products were used to calculate inorganic aerosol, dust, and absorbing non-dust AOD. Both GC and MISR suggest that, on average, inorganic aerosol has the highest AOD (GC: 0.071, MISR: 0.089) nationally, followed by absorbing non-dust species (GC: 0.025, MISR: 0.041), and dust (GC: 0.013, MISR: 0.014). The large discrepancies in our inter-comparison are due to GC underestimation of inorganic aerosol levels during all four seasons in the western U.S., and dust during summer in the eastern U.S., along with overestimation of summertime absorbing non-dust species over the northwestern U.S. These uncertainties are attributed to underestimation of inorganic aerosol emissions in more polluted western regions, the transport of Sahara dust in the summer, misuse of the fire files, and MISR retrieval uncertainties in the surface and choice of aerosol models.
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  • 76
    Publication Date: 2013-10-04
    Description: [1]  The eruption of the Icelandic volcano Eyjafjallajökull in the spring of 2010 lasted for 39 days with an explosive phase (14–18 April), an effusive phase (18 April–4 May) and a phase with renewed explosive activity (5–17 May). Images every 5 seconds from a camera mounted 34 km from the volcano are available for most of the eruption. Applying the maximum cross-correlation method (MCC) on these images, the velocity structure of the eruption cloud has been mapped in detail for four time intervals covering the three phases of the eruption. The results show that on average there are updrafts in one part of the cloud, and lateral motion or downdrafts in another. Even within the updraft part, there are alternating motions of strong updrafts, weak updrafts and downward motion. These results show a highly variable plume driven by intermittent explosions. The results are discussed in the context of integral plume models, and in terms of elementary parcel theory.
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  • 77
    Publication Date: 2013-10-04
    Description: [1]  The Madden–Julian oscillation (MJO) is the dominant mode of intraseasonal variability in tropical rainfall on the large scale, but its signal is often obscured in individual station data, where effects are most directly felt at the local level. The Fly River system, Papua New Guinea, is one of the wettest regions on Earth and is at the heart of the MJO envelope. 16-year time series of daily precipitation at 15 stations along the river system exhibit strong MJO modulation in rainfall. At each station, the difference in rainfall rate between active and suppressed MJO conditions is typically 40% of the station mean. The spread of rainfall between individual MJO events was small enough such that the rainfall distributions between wet and dry phases of the MJO were clearly separated, at the catchment level. This implies that successful prediction of the large-scale MJO envelope will have a practical use for forecasting local rainfall. In the steep topography of the New Guinea Highlands, the mean and MJO signal in station precipitation is twice that in the satellite TRMM 3B42HQ product, emphasising the need for ground truthing satellite-based precipitation measurements. A clear MJO signal is also present in the river level, which peaks simultaneously with MJO precipitation input in its upper reaches, but lags the precipitation by approximately 18 days on the flood plains.
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  • 78
    Publication Date: 2013-10-04
    Description: [1]  Many challenges remain for estimating the Antarctic ice sheet surface mass balance (SMB), which represents a major uncertainty in predictions of future sea-level rise. Validating continental scale studies is hampered by the sparse distribution of in-situ data. Here we present a 26-year mean SMB of the Fimbul ice shelf in East Antarctica between 1983–2009, and recent interannual variability since 2010. We compare these data to results of large-scale SMB studies for similar time periods, obtained from regional atmospheric modeling and remote sensing. Our in-situ data include ground penetrating radar, firn cores and mass balance stakes, and provide information on both temporal and spatial scales. The 26-year mean SMB on the Fimbul ice shelf varies between 170 and 620 kg m -2 a -1 giving a regional average value of 310 ±70 kg m -2 a -1 . Our measurements indicate higher long-term accumulation over large parts of the ice shelf compared to the large-scale studies. We also show that the variability of the mean annual SMB, which can be up to 90 %, can be a dominant factor in short-term estimates. The results emphasize the importance of using a combination of ground based validation data, regional climate models and remote sensing over a relevant time period in order to achieve a reliable SMB for Antarctica.
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  • 79
    Publication Date: 2013-10-04
    Description: [1]  A global model of sodium in the mesosphere and lower thermosphere has been developed within the framework of the National Center for Atmospheric Research's Whole Atmosphere Community Climate Model (WACCM). The standard fully-interactive WACCM chemistry module has been augmented with a chemistry scheme that includes 9 neutral and ionized sodium species. Meteoric ablation provides the source of sodium in the model and is represented as a combination of a meteoroid input function (MIF) and a parameterized ablation model. The MIF provides the seasonally and latitudinally varying meteoric flux which is modeled taking into consideration the astronomical origins of sporadic meteors and considers variations in particle entry angle, velocity,mass and the differential ablation of the chemical constituents. WACCM simulations show large variations in the sodium constituents over timescales from days to months. Seasonality of sodium constituents is strongly affected by variations in the MIF and transport via the mean meridional wind. In particular, the summer to winter hemisphere flow leads to the highest sodium species concentrations and loss rates occurring over the winter pole. In the Northern Hemisphere, this winter maximumcan be dramatically affected by stratospheric sudden warmings. Simulations of the January 2009 major warming event show that it caused a short term decrease in the sodium column over the polar cap that was followed by a factor of three increase in the following weeks. Overall, the modeled distribution of atomic sodium in WACCM agrees well with both ground-based and satellite observations. Given the strong sensitivity of the sodium layer to dynamical motions, reproducing its variability providesa stringent test of global models, and should help to constrain key atmospheric variables in this poorly sampled region of the atmosphere.
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  • 80
    Publication Date: 2013-10-04
    Description: [1]  The hydrological impact of enhancing Earth's albedo by solar radiation management is investigated using simulations from 12 Earth System models contributing to the Geoengineering Model Intercomparison Project (GeoMIP). We contrast an idealized experiment,G1, where the global mean radiative forcing is kept at pre-industrial conditions by reducing insolation while the CO 2 concentration is quadrupled, to a 4xCO 2 experiment. The reduction of evapotranspiration over land with instantaneously increasing CO 2 concentrations in both experiments largely contributes to an initial reduction in evaporation. A warming surface associated with the transient adjustment in 4xCO 2 generates an increase of global precipitation by around 6.9% with large zonal and regional changes in both directions, including a precipitation increase of 10% over Asia and a reduction of 7% for the North American summer monsoon. Reduced global evaporation persists in G1 with temperatures close to pre-industrial conditions. Global precipitation is reduced by around 4.5% and significant reductions occur over monsoonal land regions: East Asia (6%), South Africa (5%), North America (7%) and South America (6%). The general precipitation performance in models is discussed in comparison to observations. In contrast to the 4xCO 2 experiment, where the frequency of months with heavy precipitation intensity is increased by over 50% in comparison to the control, a reduction of up to 20% is simulated in G1. These changes in precipitation in both total amount and frequency of extremes, point to a considerable weakening of the hydrological cycle in a geoengineered world.
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  • 81
    Publication Date: 2013-06-06
    Description: [1]  Atmospheric circulation in a Snowball Earth is critical for determining cloud behavior, heat export from the tropics, regions of bare ice, and sea glacier flow. These processes strongly affect Snowball Earth deglaciation and the ability of oases to support photosynthetic marine life throughout a Snowball Earth. Here we establish robust aspects of the Snowball Earth atmospheric circulation by running six general circulation models with consistent Snowball Earth boundary conditions. The models produce qualitatively similar patterns of atmospheric circulation and precipitation minus evaporation. The strength of the Snowball Hadley circulation is roughly double modern at low CO 2 and greatly increases as CO 2 is increased. We force a 1D axisymmetric sea glacier model with GCM output and show that, neglecting zonal asymmetry, sea glaciers would limit ice thickness variations to O (10%). Global mean ice thickness in the 1D sea glacier model is well-approximated by a 0D ice thickness model with global mean surface temperature as the upper boundary condition. We then show that a thin-ice Snowball solution is possible in the axysymmetric sea glacier model when forced by output from all the GCMs if we use ice optical properties that favor the thin-ice solution. Finally, we examine Snowball oases for life using analytical models forced by the GCM output and find that conditions become more favorable for oases as the Snowball warms, so that the most critical time for the survival of life would be near the beginning of a Snowball Earth episode.
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  • 82
    Publication Date: 2013-06-06
    Description: [1]  Extensive measurements of aerosol number size distributions (in the size range 10 to 875 nm) carried out over the oceanic regions of Bay of Bengal and Arabian Sea during two large cruise experiments (one during pre-monsoon and the other during winter) are used to investigate the spatial distribution of aerosol size distributions in general, and that of fine particles in particular, within the marine atmospheric boundary layer. The size distributions, over northwestern Bay of Bengal, lying downwind of the continental outflow from Indo-Gangetic Plain, and over the Eastern Bay of Bengal, under the influence of East Asian outflow, showed a bimodal structure with prominent mode (100–125 nm) in the accumulation regime and weak mode (30–40 nm) in the Aitken regime during both pre-monsoon and winter seasons. While the Aitken mode was found to be relatively quite weak in the Indo Gangetic Plain outflow during both the seasons, it was prominent in the East Asian outflow regions, especially during the winter season. The distributions over the northern Arabian Sea, a region quite prone to advection of dust during pre-monsoon and summer season, showed a prominent Aitken mode (~45 nm) followed by a weaker accumulation mode during pre-monsoon season. Analysis of SeaWiFS data revealed a systematic collocation of Aitken mode aerosols and the high chlorophyll concentration in the northern Arabian Sea implying the role of ocean biogeochemistry in influencing the aerosol size distributions. Such a feature implying biogeochemical influence was not seen over eastern and northern Bay of Bengal during pre-monsoon and winter season.
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  • 83
    Publication Date: 2013-06-06
    Description: [1]  Understanding future changes in the frequency, intensity and duration of extreme events in response to increased greenhouse gas forcing is important for formulating adaptation and mitigation strategies that minimize damages to natural and human systems. We quantify transient changes in daily-scale seasonal extreme precipitation events over the U.S. using a 5-member ensemble of nested, high-resolution climate model simulations covering the 21 st century in the IPCC SRES A1B scenario. We find a strong drying trend in annual and seasonal precipitation over the Southwest in autumn, winter and spring, and over the central U.S. in summer. These changes are accompanied by statistically significant increases in dry day frequency and dry spell lengths. Our results also show substantial increases in the frequency of extreme wet events over the northwestern U.S. in autumn, winter and spring, and the eastern U.S. in spring and summer. In addition, the average precipitation intensity increases relative to the extreme precipitation intensity in all seasons and most regions, with the exception of the Southeast. Therefore, most regions receive a greater fraction of total seasonal precipitation from extreme events. These results imply fewer but heavier precipitation events in the future, leading to more frequent wet and dry extremes in most regions of the U.S. Our simulations suggest that many of these changes are likely to become statistically significant by the mid-21 st century. Given current vulnerabilities, such changes in extreme precipitation could be expected to increase stress on water resources in many areas of the U.S., including during the near-term decades.
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  • 84
    Publication Date: 2013-06-06
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  • 85
    Publication Date: 2013-06-06
    Description: [1]  Two data assimilation (DA) methods, a simple rule-based direct insertion (DI) approach and an one-dimensional ensemble Kalman filter (EnKF) method, are evaluated by assimilating snow cover fraction observations into the Community Land surface Model (CLM). The ensemble perturbation needed for the EnKF resulted in negative snowpack biases. Therefore, a correction is made to the ensemble bias using an approach that constrains the ensemble forecasts with a single unperturbed deterministic LSM run. This is shown to improve the final snow state analyses. The EnKF method produces slightly better results in higher elevation locations, whereas results indicate that the DI method has a performance advantage in lower elevation regions. In addition, the two DA methods are evaluated in terms of their overall impacts on the other land surface state variables (e.g., soil moisture) and fluxes (e.g., latent heat flux). The EnKF method is shown to have less impact overall than the DI method, and causes less distortion of the hydrological budget. However, the land surface model adjusts more slowly to the smaller EnKF increments, which leads to smaller but slightly more persistent moisture budget errors than found with the DI updates. The DI method can remove almost instantly much of the modeled snowpack, but this also allows the model system to quickly revert to hydrological balance for non-snowpack conditions.
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  • 86
    Publication Date: 2013-06-07
    Description: [1]  Airborne Multi-AXis Differential Optical Absorption Spectroscopy (AMAX-DOAS) measurements of NO 2 tropospheric vertical columns were performed over California for two months in summer 2010. The observations are compared to the NASA Ozone Monitoring Instrument (OMI) tropospheric vertical columns (data product v2.1) in two ways: (1) Median data was compared for the whole time period for selected boxes and the agreement was found to be fair (R = 0.97, slope = 1.4 ± 0.1, N = 10). (2) A comparison was performed on the mean of coincident AMAX-DOAS measurements within the area of the corresponding OMI pixels with the tropospheric NASA OMI NO 2 assigned to that pixel. The effects of different data filters were assessed. Excellent agreement and a strong correlation (R = 0.85, slope = 1.05 ± 0.09, N = 56) was found for (2) when the data was filtered to eliminate large pixels near the edge of the OMI orbit, the cloud radiance fraction was 〈 50 %, the OMI overpass occurred within 2 hr of the AMAX-DOAS measurements, the flight altitude was 〉 2 km, and a representative sample of the footprint was taken by the AMAX-DOAS instrument. The AMAX-DOAS and OMI data sets both show a reduction of NO 2 tropospheric columns on weekends by 38 ± 24 % and 33 ± 11 %, respectively. The assumptions in the tropospheric satellite air mass factor simulations were tested using independent measurements of surface albedo, aerosol extinction and NO 2 profiles for Los Angeles for July 2010 indicating an uncertainty of 12 %.
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  • 87
    Publication Date: 2013-06-08
    Description: Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from many phyla. Pnkp is composed of three catalytic modules: an N-terminal polynucleotide 5' kinase, a central 2',3' phosphatase and a C-terminal ligase. The phosphatase module is a Mn 2+ -dependent phosphodiesterase–monoesterase that dephosphorylates 2',3'-cyclic phosphate RNA ends. Here we report the crystal structure of the phosphatase domain of Clostridium thermocellum Pnkp with Mn 2+ and citrate in the active site. The protein consists of a core binuclear metallo-phosphoesterase fold (exemplified by bacteriophage phosphatase) embellished by distinctive secondary structure elements. The active site contains a single Mn 2+ in an octahedral coordination complex with Asp187, His189, Asp233, two citrate oxygens and a water. The citrate fills the binding site for the scissile phosphate, wherein it is coordinated by Arg237, Asn263 and His264. The citrate invades the site normally occupied by a second metal (engaged by Asp233, Asn263, His323 and His376), and thereby dislocates His376. A continuous tract of positive surface potential flanking the active site suggests an RNA binding site. The structure illuminates a large body of mutational data regarding the metal and substrate specificity of Clostridium thermocellum Pnkp phosphatase.
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  • 88
    Publication Date: 2013-06-08
    Description: The formation of the open promoter complex (RPo) in which the melted DNA containing the transcription start site is located at the RNA polymerase (RNAP) catalytic centre is an obligatory step in the transcription of DNA into RNA catalyzed by RNAP. In the RPo, an extensive network of interactions is established between DNA, RNAP and the -factor and the formation of functional RPo occurs via a series of transcriptional intermediates (collectively ‘RPi’). A single tryptophan is ideally positioned to directly engage with the flipped out base of the non-template strand at the +1 site. Evidence suggests that this tryptophan (i) is involved in either forward translocation or DNA scrunching and (ii) in 54 -regulated promoters limits the transcription activity of at least one intermediate complex (RPi) before the formation of a fully functional RPo. Limiting RPi activity may be important in preventing the premature synthesis of abortive transcripts, suggesting its involvement in a general mechanism driving the RPi to RPo transition for transcription initiation.
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  • 89
    Publication Date: 2013-06-08
    Description: Guanine-rich RNA sequences can fold into non-canonical, four stranded helical structures called G-quadruplexes that have been shown to be widely distributed within the mammalian transcriptome, as well as being key regulatory elements in various biological mechanisms. That said, their role within the 3'-untranslated region (UTR) of mRNA remains to be elucidated and appreciated. A bioinformatic analysis of the 3'-UTRs of mRNAs revealed enrichment in G-quadruplexes. To shed light on the role(s) of these structures, those found in the LRP5 and FXR1 genes were characterized both in vitro and in cellulo . The 3'-UTR G-quadruplexes were found to increase the efficiencies of alternative polyadenylation sites, leading to the expression of shorter transcripts and to possess the ability to interfere with the miRNA regulatory network of a specific mRNA. Clearly, G-quadruplexes located in the 3'-UTRs of mRNAs are cis -regulatory elements that have a significant impact on gene expression.
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  • 90
    Publication Date: 2013-06-08
    Description: One of the primary aims of synthetic biology is to (re)design metabolic pathways towards the production of desired chemicals. The fast pace of developments in molecular biology increasingly makes it possible to experimentally redesign existing pathways and implement de novo ones in microbes or using in vitro platforms. For such experimental studies, the bottleneck is shifting from implementation of pathways towards their initial design. Here, we present an online tool called ‘Metabolic Tinker’, which aims to guide the design of synthetic metabolic pathways between any two desired compounds. Given two user-defined ‘target’ and ‘source’ compounds, Metabolic Tinker searches for thermodynamically feasible paths in the entire known metabolic universe using a tailored heuristic search strategy. Compared with similar graph-based search tools, Metabolic Tinker returns a larger number of possible paths owing to its broad search base and fast heuristic, and provides for the first time thermodynamic feasibility information for the discovered paths. Metabolic Tinker is available as a web service at http://osslab.ex.ac.uk/tinker.aspx . The same website also provides the source code for Metabolic Tinker, allowing it to be developed further or run on personal machines for specific applications.
    Keywords: Synthetic Biology and Assembly Cloning, Computational Methods
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  • 91
    Publication Date: 2013-06-08
    Description: COHCAP (City of Hope CpG Island Analysis Pipeline) is an algorithm to analyze single-nucleotide resolution DNA methylation data produced by either an Illumina methylation array or targeted bisulfite sequencing. The goal of the COHCAP algorithm is to identify CpG islands that show a consistent pattern of methylation among CpG sites. COHCAP is currently the only DNA methylation package that provides integration with gene expression data to identify a subset of CpG islands that are most likely to regulate downstream gene expression, and it can generate lists of differentially methylated CpG islands with ~50% concordance with gene expression from both cell line data and heterogeneous patient data. For example, this article describes known breast cancer biomarkers (such as estrogen receptor) with a negative correlation between DNA methylation and gene expression. COHCAP also provides visualization for quality control metrics, regions of differential methylation and correlation between methylation and gene expression. This software is freely available at https://sourceforge.net/projects/cohcap/ .
    Keywords: Nucleic acid modification, Computational Methods, Genomics
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  • 92
    Publication Date: 2013-06-08
    Description: Tristetraprolin (TTP) and let-7 microRNA exhibit suppressive effects on cell growth through down-regulation of oncogenes. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. However, the precise mechanism of this repression is unknown. We here demonstrate that p53 stimulated by the DNA-damaging agent doxorubicin (DOX) induced the expression of TTP in cancer cells. TTP in turn increased let-7 levels through down-regulation of Lin28a . Correspondingly, cancer cells with mutations or inhibition of p53 failed to induce the expression of both TTP and let-7 on treatment with DOX. Down-regulation of TTP by small interfering RNAs attenuated the inhibitory effect of DOX on let-7 expression and cell growth. Therefore, TTP provides an important link between p53 activation induced by DNA damage and let-7 biogenesis. These novel findings provide a mechanism for the widespread decrease in TTP and let-7 and chemoresistance observed in human cancers.
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  • 93
    Publication Date: 2013-06-08
    Description: The observation that long tracts of RNA are associated with replicating molecules of mitochondrial DNA (mtDNA) suggests that the mitochondrial genome of mammals is copied by an unorthodox mechanism. Here we show that these RNA-containing species are present in living cells and tissue, based on interstrand cross-linking. Using DNA synthesis in organello , we demonstrate that isolated mitochondria incorporate radiolabeled RNA precursors, as well as DNA precursors, into replicating DNA molecules. RNA-containing replication intermediates are chased into mature mtDNA, to which they are thus in precursor–product relationship. While a DNA chain terminator rapidly blocks the labeling of mitochondrial replication intermediates, an RNA chain terminator does not. Furthermore, processed L-strand transcripts can be recovered from gel-extracted mtDNA replication intermediates. Therefore, instead of concurrent DNA and RNA synthesis, respectively, on the leading and lagging strands, preformed processed RNA is incorporated as a provisional lagging strand during mtDNA replication. These findings indicate that RITOLS is a physiological mechanism of mtDNA replication, and that it involves a ‘bootlace' mechanism, in which processed transcripts are successively hybridized to the lagging-strand template, as the replication fork advances.
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  • 94
    Publication Date: 2013-06-08
    Description: Escherichia coli Exonuclease I (ExoI) digests single-stranded DNA (ssDNA) in the 3'-5' direction in a highly processive manner. The crystal structure of ExoI, determined previously in the absence of DNA, revealed a C-shaped molecule with three domains that form a central positively charged groove. The active site is at the bottom of the groove, while an extended loop, proposed to encircle the DNA, crosses over the groove. Here, we present crystal structures of ExoI in complex with four different ssDNA substrates. The structures all have the ssDNA bound in essentially the predicted manner, with the 3'-end in the active site and the downstream end under the crossover loop. The central nucleotides of the DNA form a prominent bulge that contacts the SH3-like domain, while the nucleotides at the downstream end of the DNA form extensive interactions with an ‘anchor’ site. Seven of the complexes are similar to one another, but one has the ssDNA bound in a distinct conformation. The highest-resolution structure, determined at 1.95 Å, reveals an Mg 2+ ion bound to the scissile phosphate in a position corresponding to Mg B in related two-metal nucleases. The structures provide new insights into the mechanism of processive digestion that will be discussed.
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  • 95
    Publication Date: 2013-06-08
    Description: The rpoS mRNA, which encodes the master regulator S of general stress response, requires Hfq-facilitated base pairing with DsrA small RNA for efficient translation at low temperatures. It has recently been proposed that one mechanism underlying Hfq action is to bridge a transient ternary complex by simultaneously binding to rpoS and DsrA. However, no structural evidence of Hfq simultaneously bound to different RNAs has been reported. We detected simultaneous binding of Hfq to rpoS and DsrA fragments. Crystal structures of AU6A•Hfq•A7 and Hfq•A7 complexes were resolved using 1.8- and 1.9-Å resolution, respectively. Ternary complex has been further verified in solution by NMR. In vivo , activation of rpoS translation requires intact Hfq, which is capable of bridging rpoS and DsrA simultaneously into ternary complex. This ternary complex possibly corresponds to a meta-stable transition state in Hfq-facilitated small RNA–mRNA annealing process.
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  • 96
    Publication Date: 2013-06-11
    Description: [1]  This study presents a nonlinear spatio-temporal analysis of 1167 station temperature records from the United States Historical Climatology Network covering the period from 1898 through 2008. We use the Empirical Mode Decomposition (EMD) method to extract the generally nonlinear trends of each station. The statistical significance of each trend is assessed against three null models of the background climate variability, represented by stochastic processes of increasing temporal correlation length. We find strong evidence that more than 50 percent of all stations experienced a significant trend over the last century with respect to all three null models. A spatio-temporal analysis reveals a significant cooling trend in the South-East and significant warming trends in the rest of the contiguous US. It also shows that the warming trend appears to have migrated equatorward. This shows the complex spatio-temporal evolution of climate change at local scales.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 97
    Publication Date: 2013-06-11
    Description: [1]  Despite growing interest in the visible light absorbing organic component of atmospheric aerosols, referred to as “brown” carbon, our knowledge of its chemical composition remains limited. It is well accepted that biomass burning is one important source of “brown” carbon in the atmosphere. In this study, cloud water samples heavily affected by biomass burning were collected at Mount Tai (1534 m, ASL), located in Shandong province in the North China Plain in summer 2008. The samples were analyzed with high performance liquid chromatography equipped with a UV/Vis absorbance detector immediately followed by electrospray ionization and analysis using a time-of-flight (ToF) mass spectrometer. The high mass resolution and accuracy provided by the ToF mass spectrometer allows determination of the elemental composition of detected ions. Using this approach the elemental compositions of 16 major light absorbing compounds, which together accounted for approximately half of measured sample absorption between 300 and 400 nm, were determined. The most important classes of light absorbing compounds were found to be nitrophenols and aromatic carbonyls. Light absorption over this wavelength range by reduced nitrogen compounds was insignificant in these samples.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 98
    Publication Date: 2013-06-11
    Description: [1]  Remote sensing techniques offer the unique possibility to continuously and automatically monitor the atmospheric state from ground and space. Ground based microwave radiometers (MWRs), for example, are frequently used for temperature and humidity profiling of the lower troposphere. In order to improve the profiles in the middle and upper troposphere, further information is needed. In this respect, satellite measurements are expected to be very useful. In this study, the synergy benefit in temperature and humidity clear-sky profiling using different combinations of state-of-the-art microwave and infrared ground and satellite based instruments is assessed. The synergy benefit is regarded as the information gain in light of ground based MWR observations together with some climatological a priori knowledge. The maximum information content for this kind of synergy is estimated by assuming optimum conditions, e.g., no forward model uncertainties and a horizontal homogeneous atmosphere. For a mid-latitude site, the ground based MWR gives about 4.4 and 2.4 independent pieces of information on the temperature and humidity profile, respectively. For the temperature profile, the combination with IASI and AMSU-A/MHS increases the information by a factor of about 1.8 and 1.5, respectively, with highest benefit in warm and/or humid conditions. The vertical information on humidity is significantly improved by highly spectrally resolved IR observations from ground or space, when the atmosphere is cold and dry; the vertical information is more than tripled. If measurements from AMSU-A/MHS, IASI or SEVIRI are included, retrieval uncertainties in the middle and upper troposphere are significantly reduced by up to 68%.
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    Topics: Geosciences , Physics
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  • 99
    Publication Date: 2013-06-11
    Description: [1]  Detailed tracing of an exhaust plume from a rocket's initial trajectory is a scientifically and diagnostically useful technique. It can provide detailed information on the atmosphere's mean winds, wind shears, turbulent regime and physical state over a wide altitude range from 50 to 200 km. We analyze Soyuz rocket exhaust plumes from Plesetsk on 21 May 2009 and 27 June 2011, which uncovered significantly different atmospheric states and underlying dynamics. The first case showed highly dynamical conditions in the mesosphere, characterized by vortex structures, wind shears and small-scale turbulent eddies. The estimated turbulent energy dissipation rates ranged 330-460 mW kg −1 . A characteristic balloon-shaped trail was observed at altitudes between 105 and 160 km, having rapid expansion rates of 500-800 m s −1 over the time period of 2 min which can be explained by complex gas dynamic processes in the rocket wake involving the collision of shock waves. In the second case, we show evidence that the rocket exhaust trail persisted without any changes during its motion from Plesetsk via Denmark to the UK for 9 hours, indicating extremely stable atmospheric conditions. This case introduces a new state of the summer mesosphere – remarkably quiet conditions, probably never observed before. The rocket plumes studied, related to the initial rocket trajectory, are essentially twilight phenomena as seen from the ground using wideband spectrum cameras, that is the Sun should be below the horizon by 6°. For the first time, we analyze the dynamics of rocket exhaust products at the initial trajectory in the mesosphere and lower thermosphere using detailed photographic imaging taken from the ground.
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    Topics: Geosciences , Physics
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  • 100
    Publication Date: 2013-06-11
    Description: [1]  Rust and bunt spores that act as ice nuclei could change the formation characteristics and properties of ice-containing clouds. In addition, ice nucleation on rust and bunt spores, followed by precipitation, may be an important removal mechanism of these spores from the atmosphere. Using an optical microscope, we studied the ice nucleation properties of spores from four rust species ( Puccinia graminis , Puccinia triticina , Puccinia allii , Endocronartium harknesssii ) and two bunt species ( Tilletia laevis , Tilletia tritici ) immersed in water droplets. We show that the cumulative number of ice nuclei per spore is 5 × 10 -3 , 0.01 and 0.10 at temperatures of roughly -24 °C, -25 °C and -28 °C, respectively. Using a particle dispersion model, we also investigated if these rust and bunt spores will reach high altitudes in the atmosphere where they can cause heterogeneous freezing. Simulations suggest that after 3 days and during periods of high spore production, between 6-9 % of 15  μ m particles released over agricultural regions in Kansas (U.S.), North Dakota (U.S.), Saskatchewan (Canada) and Manitoba (Canada) can reach at least 6 km in altitude. An altitude of 6 km corresponds to a temperature of roughly -25 °C for the sites chosen. The combined results suggest that (a) ice nucleation by these fungal spores could play a role in the removal of these particles from the atmosphere and (b) ice nucleation by these rust and bunt spores are unlikely to compete with mineral dust on a global and annual scale at an altitude of approximately 6 km.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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