Caliope: an operational air quality forecasting system for the Iberian Peninsula, Balearic Islands and Canary Islands ? first annual evaluation and ongoing developments

International audienceThe Caliope project funded by the Spanish Ministry of the Environment establishes an air quality forecasting system for Spain to increase the knowledge on transport and dynamics of pollutants in Spain, to assure the accomplishment of legislation and to inform the population about the levels of pollutants, topics in which the European Commission has shown a great concern. The present contribution describes the first quantitative verification study performed so far with two chemistry transport models (CMAQ and CHIMERE) for a reference year (2004) at medium spatial resolution (around 20×20 km for the Iberian Peninsula). Both models perform similarly in the case of ground-level ozone. The mean normalised gross error MNGE remains below 15?20% during summertime, when ozone episodes occur, outlining the good skills of the system concerning the forecasting of air quality in Spain. Furthermore, the ongoing developments of the system towards high resolution modelling (4×4 km for Spain, 12×12 km for Europe, 1 h temporal resolution) and the integration with observations within the Caliope umbrella are described

Optical Aharonov-Bohm effect: an inverse hyperbolic problems approach

We describe the general setting for the optical Aharonov-Bohm effect based on the inverse problem of the identification of the coefficients of the governing hyperbolic equation by the boundary measurements. We interpret the inverse problem result as a possibility in principle to detect the optical Aharonov-Bohm effect by the boundary measurements.Comment: 34 pages. Minor changes, references adde

Discovery of new globular clusters in the Sagittarius dwarf galaxy

© ESO 2021. Published by EDP Sciences. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1051/0004-6361/202140395Context. Globular clusters (GCs) are witnesses of the past accretion events onto the Milky Way. In particular, the GCs of the Sagittarius (Sgr) dwarf galaxy are important probes of an on-going merger. Aims. Our main goal is to search for new GC members of this dwarf galaxy using the VISTA Variables in the Via Lactea Extended Survey (VVVX) near-infrared database combined with the Gaia Early Data Release 3 (EDR3) optical database. Methods. We investigated all VVVX-enabled discoveries of GC candidates in a region covering about 180 sq. deg. toward the bulge and the Sgr dwarf galaxy. We used multiband point-spread function photometry to obtain deep color-magnitude diagrams (CMDs) and luminosity functions (LFs) for all GC candidates, complemented by accurate Gaia-EDR3 proper motions (PMs) to select Sgr members and variability information to select RR Lyrae which are potential GC members. Results. After applying a strict PM cut to discard foreground bulge and disk stars, the CMDs and LFs for some of the GC candidates exhibit well defined red giant branches and red clump giant star peaks. We selected the best Sgr GCs, estimating their distances, reddenings, and associated RR Lyrae. Conclusions. We discover 12 new Sgr GC members, more than doubling the number of GCs known in this dwarf galaxy. In addition, there are 11 other GC candidates identified that are uncertain, awaiting better data for confirmation.Peer reviewedFinal Accepted Versio

Search based software engineering: Trends, techniques and applications

© ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Unraveling the Nexus: Exploring the Pathways to Combined Resource Use

In response to the unprecedented decline in global natural resource endowments, the so-called nexus framework is gaining increasing influence on resource management practices. In this research, we approach the resource nexus through the concept of nexus pathways. Nexus pathways are configurations that resource flows follow along supply chains leading to the combined use of two or more resources. Three general types of pathways are identified: direct (on-site use), dependent (one-way supply chains), and interdependent (supply-chain feedbacks). We quantify and compare each pathway by means of multiregional input-output analysis and structural path analysis, and apply this approach to a comparative case study on the water-energy nexus (WEN) in the United States and China. Interdependencies or feedbacks are generally thought to be relevant for the WEN, especially between water and energy sectors. Our economy-wide analysis for both countries indicates, however, that feedbacks neither play an important role in the WEN nor substantially take place between water and energy sectors. The most important feedbacks contribute to less than 1% of total resource use, and these take place mostly between manufacturing sectors. Overall, the studied WEN is mostly driven by dependent pathways and, to a lesser degree, direct resource use. Comparative differences between the two countries are largely explained by differences in economic structure, technology, and resource endowments. Our findings call into question current research and policy focus and suggest greater attention to less complex, but more determining, pathways leading to absolute resource use

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

The Influence of Foreign vs North American Emissions on Surface Ozone in the US

As part of the Hemispheric Transport of Air Pollution (HTAP; www.htap.org) project, we analyze results from 16 global and hemispheric chemical transport models and compare these to Clean Air Status and Trends Network (CASTNet) observations in the United States (US) for 2001. Using the policy-relevant maximum daily 8-h ozone (MDA8 O3) statistic, the multi-model ensemble represents the observations well (mean r2=0.57, ensemble bias=+4.1 ppbv for all regions and all seasons) despite a wide range in the individual model results. Correlations are strongest in the NorthEastern US during spring and fall (r2=0.68); and weakest in the Midwestern US in summer (r2=0.46). However, large positive mean biases exist during summer for all Eastern US regions, ranging from 10¿20 ppbv, and a smaller negative bias is present in the Western US during spring (3 ppbv). In most all other regions and seasons, the biases of the model ensemble simulations are 5 ppbv. Sensitivity simulations in which anthropogenic O3-precursor emissions (NOx+NMVOC+CO+aerosols) were decreased by 20% in each of four source regions: East Asia (EA), South Asia (SA), Europe (EU) and North America (NA) show that the greatest response of MDA8 O3 to the summed foreign emissions reductions occurs during spring in the West (0.9 ppbv reduction due to 20% reductions from EA+SA+EU). East Asia is the largest contributor to MDA8 O3 at all ranges of the O3 distribution for most regions (typically 0.45 ppbv). The exception is in the NorthEastern US where European emissions reductions had the greatest impact on MDA8 O3, particularly in the middle of the MDA8 O3 distribution (response of 0.35 ppbv between 35¿55 ppbv). In all regions and seasons, however, O3-precursor emissions reductions of 20% in the NA source region decrease MDA8 O3 the most by a factor of 2 to nearly 10 relative to foreign emissions reductions. The O3 response to anthropogenic NA emissions is greatest in the Eastern US during summer at the high end of the O3 distribution (5-6 ppbv for 20% reductions). While the impact of foreign emissions on surface O3 in the US is not negligible and is of increasing concern given the growth in emissions upwind of the US - domestic emissions reductions remain a farmore effective means of decreasing MDA8 O3 values, particularly those above 75 ppb(the current US standard).JRC.H.2-Air and Climat