Spatial, Temporal and Vertical Distribution of Ammonia Concentrations Over Europe – Comparing a Static and Dynamic Approach With WRF-Chem

The study focuses on the application of a dynamic ammonia emission into the Weather Research and Forecasting Chemistry model (WRF-Chem) and the influence on the simulated ammonia concentrations and the overall model performance. We have focused on agricultural ammonia sources and have analysed both hourly and daily patterns of ammonia emissions and concentrations at measurement sites located in agricultural areas or influenced by this activity. For selected episodes, we have also investigated the 3-D patterns of the ammonia concentrations in the atmosphere. The application of the dynamic ammonia emission into the WRF-Chem model (the “DYNAMIC” simulation) results in an improvement of the modelled daily ammonia concentrations in comparison to a static approach (the “BASE” simulation), which is currently widely used in chemical transport models. In the case of hourly resolution, we have observed an improvement for the DYNAMIC approach for the winter and autumn seasons, but for the entire year the modelled hourly ammonia peaks are shifted toward the afternoon hours if compared with measurements. This study indicates that the current description of the diurnal cycle of the ammonia concentration from fields is not accurate and more research is needed in order to improve the processes that describe the emission from fertilised fields. The results suggest that the governing processes in relation to the diurnal cycle are the atmospheric mixing and the emission strength. Therefore,an improved description of the diurnal profile of ammonia concentrations within atmospheric models requires a better description of the planetary boundary layer height and a stronger daily pattern of ammonia emission, e.g. through increased evaporation or increased fluxes from the surface

Ammonia Concentrations Over Europe – Application of the WRF-Chem Model Supported With Dynamic Emission

The study focuses on the application of a static and dynamic ammonia emission based on a Europe-wide default setting into the Weather Research and Forecasting Chemistry model (WRF-Chem) and the influence on the simulated ammonia concentrations and the overall model performance. The WRF-Chem model was run twice for the entire Europe at a spatial resolution of 36 x 36 km for the year 2012. In the first simulation we used a static emission approach (the “BASE” simulation), whereas in the second simulation, dynamic ammonia emissions were used (the “DYNAMIC” simulation). Both simulations underestimate measured concentrations of NH3 for all seasons, have similar NMGE (about 0.7 μg m-3) and modelled hourly ammonia peaks are shifted towards the afternoon hours if compared with measurements. However, for all temporal resolutions, normalised mean gross error in winter and summer is lower for DYNAMIC than for BASE. The DYNAMIC simulation also generally gives worse performance in spring for each temporal resolution. For further improvement of the modelled ammonia concentrations with WRF-Chem we suggest to use a nested approach with higher spatial resolution, which will lead to better separation of the ammonia source regions from surrounding areas, and take into account national practice and regulations in the emission model, eventually only in the nested model domain

Are Estimates of Wind Characteristics Based on Measurements with Pitot Tubes and GNSS Receivers Mounted on Consumer-grade Unmanned Aerial Vehicles Applicable in Meteorological Studies?

The objective of this paper is to empirically show that estimates of wind speed and wind direction based on measurements carried out using the Pitot tubes and GNSS receivers, mounted on consumer-grade unmanned aerial vehicles (UAVs), may accurately approximate true wind parameters. The motivation for the study is that a growing number of commercial and scientific UAV operations may soon become a new source of data on wind speed and wind direction, with unprecedented spatial and temporal resolution. The feasibility study was carried out within an isolated mountain meadow of Polana Izerska located in the Izera Mountains (SW Poland) during an experiment which aimed to compare wind characteristics measured by several instruments: three UAVs (swinglet CAM, eBee, Maja) equipped with the Pitot tubes and GNSS receivers, wind speed and direction meters mounted at 2.5 m and 10 m (mast), conventional weather station and vertical sodar. The three UAVs performed seven missions along spiral-like trajectories, most reaching 130 m above take-off location. The estimates of wind speed and wind direction were found to agree between UAVs. The time series of wind speed measured at 10 m were extrapolated to flight altitudes recorded at a given time so that a comparison was made feasible. It was found that the wind speed estimates provided by the UAVs on a basis of the Pitot tube/GNSS data are in agreement with measurements carried out using dedicated meteorological instruments. The discrepancies were recorded in the first and last phases of UAV flights

Mass spectrometry-based determination of Kallikrein-related peptidase 7 (KLK7) cleavage preferences and subsite dependency

Published online: 28 July 2017The cleavage preferences of Kallikrein-related peptidase 7 (KLK7) have previously been delineated using synthetic peptide libraries of fixed length, or single protein chains and have suggested that KLK7 exerts a chymotryptic-like cleavage preference. Due to the short length of the peptides utilised, only a limited number of subsites have however been assessed. To determine the subsite preferences of KLK7 in a global setting, we used a mass spectrometry (MS)-based in-depth proteomics approach that utilises human proteome-derived peptide libraries of varying length, termed Proteomic Identification of protease Cleavage Sites (PICS). Consistent with previous findings, KLK7 was found to exert chymotryptic-like cleavage preferences. KLK7 subsite preferences were also characterised in the P2-P2' region, demonstrating a preference for hydrophobic residues in the non-prime and hydrophilic residues in the prime subsites. Interestingly, single catalytic triad mutant KLK7 (mKLK7; S195A) also showed residual catalytic activity (kcat/KM = 7.93 × 10²s⁻¹M⁻¹). Catalytic inactivity of KLK7 was however achieved by additional mutation in this region (D102N). In addition to characterising the cleavage preferences of KLK7, our data thereby also suggests that the use of double catalytic triad mutants should be employed as more appropriate negative controls in future investigations of KLK7, especially when highly sensitive MS-based approaches are employed.Lakmali Munasinghage Silva, Thomas Stoll, Thomas Kryza, Carson Ryan Stephens, Marcus Lachlan Hastie, Helen Frances Irving-Rodgers, Ying Dong, Jeffrey John Gorman and Judith Ann Clement

THE ATLAS EXPERIMENT ON-LINE MONITORING AND FILTERING AS AN EXAMPLE OF REAL-TIME APPLICATION

The ATLAS detector, recording LHC particles’ interactions, produces events with rate of40 MHz and size of 1.6 MB. The processes with new and interesting physics phenomena arevery rare, thus an efficient on-line filtering system (trigger) is necessary. The asynchronouspart of that system relays on few thousands of computing nodes running the filtering software.Applying refined filtering criteria results in increase of processing times what may lead tolack of processing resources installed on CERN site. We propose extension to this part ofthe system based on submission of the real-time filtering tasks into the Grid

The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer

Kallikrein-related peptidase 14 (KLK14) is one of several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumour microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analysed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic and in vitro assays with the goal to identify substrates, related-signalling pathways and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neo-adjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression re-occurred in patients who developed castrate-resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14-substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14-regulated genes (Interleukin 32, midkine, Sox9), particularly an involvement of the MAPK1 and IL1RN pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumours. Additional work is necessary to determine the benefits and implications of targeting/co-targeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment

U–Pb Zircon geochronology of the Cambro-Ordovician metagranites and metavolcanic rocks of central and NW Iberia

New U–Pb zircon data from metagranites and metavolcanic rocks of the Schist-Graywacke Complex Domain and the Schistose Domain of Galicia Tras-os-Montes Zone from central and NW Iberia contribute to constrain the timing of the Cambro-Ordovician magmatism from Central Iberian and Galicia Tras-os-Montes Zones which occurred between 498 and 462 Ma. The crystallization ages of the metagranites and metavolcanic rocks from the northern Schist-Graywacke Complex Domain are as follows: (a) in west Salamanca, 489 ± 5 Ma for Vitigudino, 486 ± 6 Ma for Fermoselle and 471 ± 7 Ma for Ledesma; (b) in northern Gredos, 498 ± 4 Ma for Castellanos, 492 ± 4 Ma for San Pelayo and 488 ± 3 Ma for Bercimuelle; (c) in Guadarrama, 490 ± 5 Ma for La Estacion I, 489 ± 9 Ma for La Canada, 484 ± 6 Ma for Vegas de Matute (leucocratic), 483 ± 6 Ma for El Cardoso, 482 ± 8 Ma for La Morcuera, 481 ± 9 Ma for Buitrago de Lozoya, 478 ± 7 Ma for La Hoya, 476 ± 5 Ma for Vegas de Matute (melanocratic), 475 ± 5 Ma for Riaza, 473 ± 8 Ma for La Estacion II and 462 ± 11 Ma for La Berzosa; and (d) in Toledo, 489 ± 7 Ma for Mohares and 480 ± 8 Ma for Polan. The crystallization ages of the metagranites from the Schistose Domain of Galicia Tras-os-Montes Zone are 497 ± 6 Ma for Laxe, 486 ± 8 Ma for San Mamede, 482 ± 7 Ma for Bangueses, 481 ± 5 Ma for Noia, 480 ± 10 for Rial de Sabucedo, 476 ± 9 Ma for Vilanova, 475 ± 6 Ma for Pontevedra, 470 ± 6 Ma for Cherpa and 462 ± 8 Ma for Bande.This magmatism is characterized by an average isotopic composition of (87Sr/86Sr)485Ma ≈ 0.712, (eNd)485Ma ≈ -4.1 and (TDM) ≈ 1.62 Ga, and a high zircon inheritance, composed of Ediacaran–Early Cambrian (65 %) and, to a lesser extent, Cryogenian, Tonian, Mesoproterozoic, Orosirian and Archean pre-magmatic cores. Combining our geochronological and isotopic data with others of similar rocks from the European Variscan Belt, it may be deduced that Cambro-Ordovician magmas from this belt were mainly generated by partial melting of Ediacaran–Early Cambrian igneous rocks

Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer (vol 313, pg 1347, 2015)

Heli Nevanlinna ja Kristiina Aittomäki ovat CIMBA Consortium -työryhmän jäseniä.IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317(12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682(6%) with ovarian cancer, 272(2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% Cl, 1.22-1.74; P = 2 x 10(-6)), c.4328 to c.4945 (BCCR2; RH R = 1.34; 95% Cl, 1.01-1.78; P =.04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% Cl, 1.22-1.55; P = 6 x 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% Cl, 0.56-0.70; P = 9 x 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% Cl, 1.06-2.78; P =.03), c.772 to c.1806 (BCCRI; RHR = 1.63; 95% Cl, 1.10-2.40; P =.01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% Cl, 1.69-3.16; P =.00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% Cl, 0.44-0.60; P = 6 x 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% Cl, 0.41-0.80; P =.001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.Peer reviewe

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers