Evaluating wind profiles in a numerical weather prediction model with Doppler lidar

We use Doppler lidar wind profiles from six locations around the globe to evaluate the wind profile forecasts in the boundary layer generated by the operational global Integrated Forecast System (IFS) from the European Centre for Medium-range Weather Forecasts (ECMWF). The six locations selected cover a variety of surfaces with different characteristics (rural, marine, mountainous urban, and coastal urban). We first validated the Doppler lidar observations at four locations by comparison with co-located radiosonde profiles to ensure that the Doppler lidar observations were of sufficient quality. The two observation types agree well, with the mean absolute error (MAE) in wind speed almost always less than 1 m s−1. Large deviations in the wind direction were usually only seen for low wind speeds and are due to the wind direction uncertainty increasing rapidly as the wind speed tends to zero. Time–height composites of the wind evaluation with 1 h resolution were generated, and evaluation of the model winds showed that the IFS model performs best over marine and coastal locations, where the mean absolute wind vector error was usually less than 3 m s−1 at all heights within the boundary layer. Larger errors were seen in locations where the surface was more complex, especially in the wind direction. For example, in Granada, which is near a high mountain range, the IFS model failed to capture a commonly occurring mountain breeze, which is highly dependent on the sub-grid-size terrain features that are not resolved by the model. The uncertainty in the wind forecasts increased with forecast lead time, but no increase in the bias was seen. At one location, we conditionally performed the wind evaluation based on the presence or absence of a low-level jet diagnosed from the Doppler lidar observations. The model was able to reproduce the presence of the low-level jet, but the wind speed maximum was about 2 m s−1 lower than observed. This is attributed to the effective vertical resolution of the model being too coarse to create the strong gradients in wind speed observed. Our results show that Doppler lidar is a suitable instrument for evaluating the boundary layer wind profiles in atmospheric models.</p

Wind and Turbulence Statistics in the Urban Boundary Layer over a Mountain–Valley System in Granada, Spain

Urban boundary layer characterization is currently a challenging and relevant issue, because of its role in weather and air quality modelling and forecast. In many cities, the effect of complex topography at local scale makes this modelling even more complicated. This is the case of mid-latitude urban areas located in typical basin topographies, which usually present low winds and high turbulence within the atmospheric boundary layer (ABL). This study focuses on the analysis of the first ever measurements of wind with high temporal and vertical resolution throughout the ABL over a medium-sized city surrounded by mountains in southern Spain. These measurements have been gathered with a scanning Doppler lidar system and analyzed using the Halo lidar toolbox processing chain developed at the Finnish Meteorological Institute. We have used the horizontal wind product and the ABL turbulence classification product to carry out a statistical study using a two-year database. The data availability in terms of maximum analyzed altitudes for statistically significant results was limited to around 1000–1500 m above ground level (a.g.l.) due to the decreasing signal intensity with height that also depends on aerosol load. We have analyzed the differences and similarities in the diurnal evolution of the horizontal wind profiles for different seasons and their modelling with Weibull and von Mises probability distributions, finding a general trend of mean daytime wind from the NW with mean speeds around 3–4 m/s at low altitudes and 6–10 m/s at higher altitudes, and weaker mean nocturnal wind from the SE with similar height dependence. The highest speeds were observed during spring, and the lowest during winter. Finally, we studied the turbulent sources at the ABL with temporal (for each hour of the day) and height resolution. The results show a clear convective activity during daytime at altitudes increasing with time, and a significant wind-shear-driven turbulence during night-time

Wind and Turbulence Statistics in the Urban Boundary Layer over a Mountain–Valley System in Granada, Spain

Urban boundary layer characterization is currently a challenging and relevant issue, because of its role in weather and air quality modelling and forecast. In many cities, the effect of complex topography at local scale makes this modelling even more complicated. This is the case of mid-latitude urban areas located in typical basin topographies, which usually present low winds and high turbulence within the atmospheric boundary layer (ABL). This study focuses on the analysis of the first ever measurements of wind with high temporal and vertical resolution throughout the ABL over a medium-sized city surrounded by mountains in southern Spain. These measurements have been gathered with a scanning Doppler lidar system and analyzed using the Halo lidar toolbox processing chain developed at the Finnish Meteorological Institute. We have used the horizontal wind product and the ABL turbulence classification product to carry out a statistical study using a two-year database. The data availability in terms of maximum analyzed altitudes for statistically significant results was limited to around 1000–1500 m above ground level (a.g.l.) due to the decreasing signal intensity with height that also depends on aerosol load. We have analyzed the differences and similarities in the diurnal evolution of the horizontal wind profiles for different seasons and their modelling with Weibull and von Mises probability distributions, finding a general trend of mean daytime wind from the NW with mean speeds around 3–4 m/s at low altitudes and 6–10 m/s at higher altitudes, and weaker mean nocturnal wind from the SE with similar height dependence. The highest speeds were observed during spring, and the lowest during winter. Finally, we studied the turbulent sources at the ABL with temporal (for each hour of the day) and height resolution. The results show a clear convective activity during daytime at altitudes increasing with time, and a significant wind-shear-driven turbulence during night-time

Structural and Functional Insights Into Lysostaphin-Substrate Interaction

cell wall. Scission of these cross-links is carried out by its N-terminal catalytic domain, a zinc-dependent endopeptidase. Understanding the determinants affecting the efficiency of catalysis and strength and specificity of interactions lies at the heart of all lysostaphin family enzyme applications. To this end, we have used NMR, SAXS and molecular dynamics simulations to characterize lysostaphin structure and dynamics, to address the inter-domain interaction, the enzyme-substrate interaction as well as the catalytic properties of pentaglycine cleavage in solution. Our NMR structure confirms the recent crystal structure, yet, together with the molecular dynamics simulations, emphasizes the dynamic nature of the loops embracing the catalytic site. We found no evidence for inter-domain interaction, but, interestingly, the SAXS data delineate two preferred conformation subpopulations. Catalytic H329 and H360 were observed to bind a second zinc ion, which reduces lysostaphin pentaglycine cleaving activity. Binding of pentaglycine or its lysine derivatives to the targeting domain was found to be of very low affinity. The pentaglycine interaction site was located to the N-terminal groove of the domain. Notably, the targeting domain binds the peptidoglycan stem peptide Ala-d-γ-Glu-Lys-d-Ala-d-Ala with a much higher, micromolar affinity. Binding site mapping reveals two interaction sites of different affinities on the surface of the domain for this peptide

Choice Architecture Cueing to Healthier Dietary Choices and Physical Activity at the Workplace:Implementation and Feasibility Evaluation

Redesigning choice environments appears a promising approach to encourage healthier eating and physical activity, but little evidence exists of the feasibility of this approach in real-world settings. The aim of this paper is to portray the implementation and feasibility assessment of a 12-month mixed-methods intervention study, StopDia at Work, targeting the environment of 53 diverse worksites. The intervention was conducted within a type 2 diabetes prevention study, StopDia. We assessed feasibility through the fidelity, facilitators and barriers, and maintenance of implementation, building on implementer interviews (n = 61 informants) and observations of the worksites at six (t1) and twelve months (t2). We analysed quantitative data with Kruskall–Wallis and Mann–Whitney U tests and qualitative data with content analysis. Intervention sites altogether implemented 23 various choice architectural strategies (median 3, range 0–14 strategies/site), employing 21 behaviour change mechanisms. Quantitative analysis found implementation was successful in 66%, imperfect in 25%, and failed in 9% of evaluated cases. These ratings were independent of the ease of implementation of applied strategies and reminders that implementers received. Researchers’ assistance in intervention launch (p = 0.02) and direct contact to intervention sites (p < 0.001) predicted higher fidelity at t1, but not at t2. Qualitative content analysis identified facilitators and barriers related to the organisation, intervention, worksite environment, implementer, and user. Contributors of successful implementation included apt implementers, sufficient implementer training, careful planning, integration into worksite values and activities, and management support. After the study, 49% of the worksites intended to maintain the implementation in some form. Overall, the choice architecture approach seems suitable for workplace health promotion, but a range of practicalities warrant consideration while designing real-world implementation

Rational design, optimization, and biological evaluation of novel α-Phosphonopropionic acids as covalent inhibitors of Rab geranylgeranyl transferase

Rab geranylgeranyltransferase (GGTase-II, RGGT) catalyses the post-translational modification of eukaryotic Rab GTPases, proteins implicated in several pathologies, including cancer, diabetes, neurodegenerative, and infectious diseases. Thus, RGGT inhibitors are believed to be a potential platform for the development of drugs and tools for studying processes related to the abnormal activity of Rab GTPases. Here, a series of new alpha-phosphonocarboxylates have been prepared in the first attempt of rational design of covalent inhibitors of RGGT derived from non-covalent inhibitors. These compounds were equipped with electrophilic groups capable of binding cysteines, which are present in the catalytic cavity of RGGT. A few of these analogues have shown micromolar activity against RGGT, which correlated with their ability to inhibit the proliferation of the HeLa cancer cell line. The proposed mechanism of this inhibitory activity was rationalised by molecular docking and mass spectrometric measurements, supported by stability and reactivity studies

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

Molecular basis of filamin a-filGAP interaction and its impairment in congenital disorders associated with filamin a mutations

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