345 research outputs found

    A new approach to turbulence modeling

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    A new approach to Reynolds averaged turbulence modeling is proposed which has a computational cost comparable to two equation models but a predictive capability approaching that of Reynolds stress transport models. This approach isolates the crucial information contained within the Reynolds stress tensor, and solves transport equations only for a set of 'reduced' variables. In this work, Direct Numerical Simulation (DNS) data is used to analyze the nature of these newly proposed turbulence quantities and the source terms which appear in their respective transport equations. The physical relevance of these quantities is discussed and some initial modeling results for turbulent channel flow are presented

    Comparison of nitric oxide measurements in the mesosphere and lower thermosphere from ACE-FTS, MIPAS, SCIAMACHY, and SMR

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    We compare the nitric oxide measurements in the mesosphere and lower thermosphere (60 to 150 km) from four instruments: ACE-FTS, MIPAS, SCIAMACHY, and SMR. We use the daily zonal mean data in that altitude range for the years 2004-2010 (ACE-FTS), 2005-2012 (MIPAS), 2008-2012 (SCIAMACHY), and 2003-2012 (SMR). We first compare the data qualitatively with respect to the morphology, focussing on the major features, and then compare the time series directly and quantitatively. In three geographical regions, we compare the vertical density profiles on coincident measurement days. Since none of the instruments delivers continuous daily measurements in this altitude region, we carried out a multi-linear regression analysis. This regression analysis considers annual and semi-annual variability in form of harmonic terms and inter-annual variability by responding linearly to the solar Lyman-alpha; radiation index and the geomagnetic Kp index. This analysis helps to find similarities and differences in the individual data sets with respect to the inter-annual variations caused by geomagnetic and solar variability. We find that the data sets are consistent and that they only disagree on minor aspects. SMR and ACE-FTS deliver the longest time series in the mesosphere and they both agree remarkably well. The shorter time series from MIPAS and SCIAMACHY also agree with them where they overlap. The data agree within ten to twenty percent when the number densities are large, but they can differ by 50 to 100% in some cases

    The clinical use of longitudinal bio-electrical impedance vector analysis in assessing stabilization of children with severe acute malnutrition

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    Background & aims: Severe Acute Malnutrition (SAM) in children is determined using anthropometry. However, bio-electrical impedance (BI) analysis could improve the estimation of altered body composition linked to edema and/or loss of lean body mass in children with SAM. We aimed to assess: 1) the changes in BI parameters during clinical stabilization and 2) whether BI parameters add prognostic value for clinical outcome beyond the use of anthropometry. Methods: This prospective observational study enrolled children, aged 6–60 months, that were admitted at Queen Elizabeth Central Hospital in Blantyre, Malawi, for complicated SAM (i.e., having either severe wasting or edematous SAM with a complicating illness). Height, weight, mid-upper arm circumference (MUAC), and BI were measured on admission and after clinical stabilization. BI measures were derived from height-adjusted indices of resistance (R/H), reactance (Xc/H), and phase angle (PA) and considered to reflect body fluids and soft tissue in BI vector analysis (BIVA). Results: We studied 183 children with SAM (55% edematous; age 23.0 ± 12.0 months; 54% male) and 42 community participants (age 20.1 ± 12.3 months; male 62%). Compared to community participants, the BIVA of children with edematous SAM were short with low PA and positioned low on the hydration axis which reflects severe fluid retention. In contrast, children with severe wasting had elongated vectors with a PA that was higher than children with edematous SAM but lower than community participants. Their BIVA position fell within the top right quadrant linked to leanness and dehydration. BIVA from severely wasted and edematous SAM patients differed between groups and from community children both at admission and after stabilization (p < 0.001). Vector position shifted during treatment only in children with edematous SAM (p < 0.001) and showed a upward translation suggestive of fluid loss. While PA was lower in children with SAM, PA did not contribute more than anthropometry alone towards explaining mortality, length of stay, or time-to-discharge or time-to-mortality. The variability and heterogeneity in BI measures was high and their overall added predictive value for prognosis of individual children was low. Conclusions: BIVA did not add prognostic value over using anthropometry alone to predict clinical outcome. Several implementation challenges need to be optimized. Thus, in low-resource settings, the routine use of BI in the management of pediatric malnutrition is questionable without improved implementation

    NRLMSIS 2.1: An Empirical Model of Nitric Oxide Incorporated Into MSIS

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    We have developed an empirical model of nitric oxide (NO) number density at altitudes from similar to 73 km to the exobase, as a function of altitude, latitude, day of year, solar zenith angle, solar activity, and geomagnetic activity. The model is part of the NRLMSIS (R) 2.1 empirical model of atmospheric temperature and species densities; this upgrade to NRLMSIS 2.0 consists solely of the addition of NO. MSIS 2.1 assimilates observations from six space-based instruments: UARS/HALOE, SNOE, Envisat/MIPAS, ACE/FTS, Odin/SMR, and AIM/SOFIE. We additionally evaluated the new model against independent extant NO data sets. In this paper, we describe the formulation and fitting of the model, examine biases between the data sets and model and among the data sets, compare with another empirical NO model (NOEM), and discuss scientific aspects of our analysis

    In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

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    The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

    Autophagy diminishes the early interferon- ? response to influenza A virus resulting in differential expression of interferon- stimulated genes

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    Influenza A virus (IAV) infection perturbs metabolic pathways such as autophagy, a stress-induced catabolic pathway that crosstalks with cellular inflammatory responses. However, the impact of autophagy perturbation on IAV gene expression or host cell responses remains disputed. Discrepant results may be a reflection of in vivo studies using cell-specific autophagy-related (Atg) gene-deficient mouse strains, which do not delineate modification of developmental programmes from more proximal effects on inflammatory response. In vitro experiments can be confounded by gene expression divergence in wild-type cultivated cell lines, as compared to those experiencing long-term absence of autophagy. With the goal to investigate cellular processes within cells that are competent or incompetent for autophagy, we generated a novel experimental cell line in which autophagy can be restored by ATG5 protein stabilization in an otherwise Atg5-deficient background. We confirmed that IAV induced autophagosome formation and p62 accumulation in infected cells and demonstrated that perturbation of autophagy did not impact viral infection or replication in ATG5-stablized cells. Notably, the induction of interferon-stimulated genes (ISGs) by IAV was diminished when cells were autophagy competent. We further demonstrated that, in the absence of ATG5, IAV-induced interferon-β (IFN-β) expression was increased as compared to levels in autophagy-competent lines, a mechanism that was independent of IAV non-structural protein 1. In sum, we report that induction of autophagy by IAV infection reduces ISG expression in infected cells by limiting IFN-β expression, which may benefit viral replication and spread

    Simulation study for the Stratospheric Inferred Winds (SIW) sub-millimeter limb sounder

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    Stratospheric Inferred Winds (SIW) is a Swedish mini sub-millimeter limb sounder selected for the 2nd InnoSat platform, with launch planned for around 2022. It is intended to fill the altitude gap between 30 and 70 km in atmospheric wind measurements and also aims at pursuing the limb observations of temperature and key atmospheric constituents between 10 and 90 km when current satellite missions will probably come to an end. Line-of-sight winds are retrieved from the Doppler shift of molecular emission lines introduced by the wind field. Observations will be performed with two antennas pointing toward the limb in perpendicular directions in order to reconstruct the 2-D horizontal wind vector. Each antenna has a vertical field of view (FOV) of 5 km. The chosen spectral band, near 655 GHz, contains a dense group of strong O3 lines suitable for exploiting the small amount of wind information in stratospheric spectra. Using both sidebands of the heterodyne receiver, a large number of chemical species will be measured, including O3 isotopologues, H2O, HDO, HCl, ClO, N2O, HNO3, NO, NO2, HCN, CH3CN and HO2. This paper presents a simulation study that assesses measurement performance. The line-of-sight winds are retrieved between 30 and 90 km with the best sensitivity between 35 and 70 km, where the precision (1σ) is 5-10 mĝ€†sĝ\u271 for a single scan. Similar performance can be obtained during day and night conditions except in the lower mesosphere, where the photo-dissociation of O3 in daytime reduces the sensitivity by 50 % near 70 km. Profiles of O3, H2O and temperature are retrieved with high precision up to 50 km ( &lt; 1 %, &lt; 2 %, 1 K, respectively). Systematic errors due to uncertainties in spectroscopic parameters, in the radiometer sideband ratio and in the radiance calibration process are investigated. A large wind retrieval bias of 10-30 mĝ€†sĝ\u271 between 30 and 40 km could be induced by the air-broadening parameter uncertainties of O3 lines. This highlights the need for good knowledge of these parameters and for studying methods to mitigate the retrieval bias.
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