Acoplamiento del modelo regional de calidad de aire (CMAQ) con el modelo de emisiones locales mediante elementos finitos

Existen modelos regionales de calidad del aire que son muy utilizados. Estos modelos tienen modelos para estudiar el aporte de contaminantes provocados por fuentes importantes de contaminación, como pueden ser chimeneas, o poligonos industriales. El modelo regional que estudiamos en este trabajo es el CMAQ (Community Multiscale Air Quality), que usa el Plume-in-Grid (PinG) como modelo para estudiar el aporte de fuentes locales de contaminación. El PinG és un modelo lagrangiano de pluma gausiana, y en este trabajo queremos cambiar esta estratégia de modelación de emisores puntuales por un modelo euleriano por elementos finitos. Para poder conseguir la integración, mallamos nuestro volumen de estudio, mediante una estratégia que nos permite la fácil integración de los tetrahedros de nuestro modelo de elementos finitos, con los elementos del modelo regional. Tambien necesitamos interpolar el campo de viento que nos da el modelo regional para conocer el campo de viento los nodos de nuestro dominio. Finalmente necesitamos usar los valores de contaminación del modelo regional en nuestro modelo local

Local scale air quality model system for diagnostic and forecasting simulations using the finite element method

Air pollution is an important topic with a great social impact; it is related with public health, environment and ecology, and climate change. Scientists have developed several models in the last thirty years, and regional air quality operational systems are used routinely by governments and agencies. Efforts have also been done to simulate the air quality in the local scale; main models are Gaussian and Puff models, that are based on a Lagrangian approach. In contrast with these models, in this thesis we have developed a system using an Eulerian approach. This model is specifically designed for regions with complex orography where the Lagrangian models have problems computing the trajectory of the particles. This model can be used for diagnostic or prediction simulations. Air quality operational systems depend on the orography, meteorological data, and emission data. Air quality models use processors to incorporate these data into the model. The data can come from numerical weather prediction systems, experimental data, or databases. In this thesis we have developed processors, specifically designed for the local scale, to incorporate these data into our system. To incorporate the orography, we have developed a mesh generation algorithm suitable for complex terrain discretization; it also allows to insert layers that can match the regional models. A wind field model has also been used; it can interpolate a three-dimensional wind field from some station measurements using a log-linear vertical wind profile, or can interpolate it from a numerical weather prediction system. Once an interpolated wind field is computed, a mass-consistent model is applied to ensure null divergence and impermeability in the terrain. The wind field is modified to take into account the injection of the pollutants into the atmosphere. Briggs studied the trajectory of the plume rise giving some empirical equations that will be used in our model. Briggs' equations describe the trajectory in a plane; our model will modify this trajectory adapting it to the ambient wind field. This modification allows the plume rise to surround the mountains or channel into the valleys. The transport and reaction of pollutants in the atmosphere is then computed using an splitting method, so the transport and the chemical reactions are computed independently. To solve the transport of pollutants we have used a finite element method stabilized using least squares. The chemical reaction is simulated using simplified models such as RIVAD, or more complex ones such as CB05. To obtain more accurate results we have used adaptation. An error indicator has been used to adapt the mesh to the solution. To adapt the mesh to the concentration distribution of all the species is very demanding, for this reason we have used a multimesh method where every chemical specie has its own mesh where we solve the transport and the chemical reactions are simulated in a common mesh. The system developed in this thesis has diagnostic and forecasting capabilities. For this reason we present two different applications. The first one is a diagnostic application in La Palma island (Spain), where wind measurements are given, and SO2 and NO2 emissions from a stack are considered. The topography of the island is real, from a digital elevation model, but the wind field measurements, and the stack location and emissions, are simulated. The second application is a forecasting application data from the CMAQ benchmark test. It is located in the surrounding of Pineville Kentucky. In this application we have used all the data from CMAQ and the chemical reaction model CB05.La contaminació atmosfèrica té gran impacte social; està relacionada ambla salut pública, l'ecologia, el medi ambient i el canvi climàtic. En els últims trenta anys, els científics han desenvolupat diversos models que els governs i les agències mediambientals utilitzen diàriament. També s'han fet esforços per simular la qualitat de l'aire en l'escala local. Els models principals són els models Gaussians i Puff, que es basen en una descripció Lagrangiana. En contrast amb aquests models, en aquesta tesi s'ha desenvolupat un sistema que utilitza una descripció Euleriana. Aquest model està dissenyat específicament per a les regions amb topografia complexa on els models Lagrangians tenen problemes calculant la trajectòria de les partícules. El model presentat en aquesta tesi pot ser utilitzat tant pel diagnòstic com per la predicció. Els sistemes operatius utilitzats actualment depenen de l'orografia, de dades meteorològiques i de dades d'emissió. Per tal d'incorporar aquestes dades, els models de qualitat de l'aire han desenvolupat diferents preprocessadors. Les dades poden venir dels sistemes numèrics de predicció meteorològics, de dades experimentals o de bases de dades. En aquesta tesi hem desenvolupat preprocessadors dissenyats específicament per a l'àmbit local, per tal d'incorporar aquestes dades al nostre sistema. Per incorporar l'orografia, hem desenvolupat un algoritme de generació de malles adequat per terreny complex; l'algoritme també ens permet inserir capes que poden coincidir amb la dels models regionals. S'ha desenvolupat un model de càlcul de camp de vent; a partir de les dades s'interpola un camp de vent tridimensional fent servir un perfil log-lineal vertical del vent, o s'interpola a partir dels resultats d'un sistema de predicció meteorològica. Quan s'ha calculat el vent interpolat, es fa servir un model de massa consistent per obtenir un camp de vent definitiu on s'ha imposat divergència zero i impermeabilitat del terreny. El camp de vent s'ha de modificar per tenir en compte la injecció dels contaminants a l'atmosfera. Briggs va estudiar la trajectòria de l'elevació de la ploma i va trobar equacions empíriques que utilitzarem en el nostre model. Les equacions de Briggs descriuen la trajectòria de la ploma en un pla vertical; el nostre model modificarà aquesta trajectòria adaptant-la al camp de vent ambiental. Aquesta modificació permet que l'elevació de la ploma rodegi les muntanyes o s'acanali a les valls. El transport i la reacció de contaminants a l'atmosfera es calcula utilitzant un mètode de "splitting", de manera que el transport i la reacció química es calculen de forma independent. Per resoldre el transport de contaminants, hem utilitzat el mètode d'elements finits estabilitzat amb mínims quadrats. La reacció química es simula mitjançant models simplificats com el model RIVAD, o més complexes com el CB05. Per obtenir resultats més precisos hem adaptat la malla a la solució utilitzant un indicador d'error. Haver d'adaptar la malla a la distribució de la concentració de totes les espècies contaminants és molt exigent i per aquest motiu hem utilitzat un mètode "multimesh" on cada espècie química té la seva pròpia malla on resolem el transport i les reaccions químiques es simulen en una malla comú. El sistema desenvolupat en aquesta tesi té capacitats de diagnòstic i pronòstic. Per aquesta raó es presenten dues aplicacions diferents. La primera és una aplicació de diagnòstic a l'illa de la Palma (Espanya), on es disposa de mesures de vent, i de les emissions de SO2 i NO2 d'una xemeneia. La topografia de l'illa és real, a partir d'un model digital del terreny, però les dades del camp de vent, la ubicació de la xemeneia i el valor de les emissions són simulades. La segona aplicació és una aplicació de predicció fent servir els resultats del benchmark del CMAQ. Es simula una zona a Pineville Kentucky. En aquesta aplicació hem utilitzat totes les dades del CMAQ i el model químic CB05

Graph-grammar based algorithm for asteroid tsunami simulations

On January 18, 2022, around 1 million kilometers from Earth, five times the distance from Earth to the Moon, a large asteroid passed without harm to the Earth. Theoretically, however, the event of the asteroid falling into Earth, causing the tsunami, is possible since there are over 27,000 near-Earth asteroids [1], and the Earth’s surface is covered in 71 percent by water. We introduce a novel graph-grammar-based framework for asteroid tsunami simulations. Our framework adaptively generates the computational mesh of the Earth model. It is built from triangular elements representing the seashore and the seabed. The computational mesh is represented as a graph, with graph vertices representing the computational mesh element’s interiors and edges. Mesh refinements are often performed by the longest-edge refinement algorithm. We have expressed this algorithm by only two graph-grammar productions. The resulting graph represents the terrain approximating the topography with a prescribed accuracy. We generalize the graph-grammar mesh refinement algorithm to work on the entire Earth model, allowing the generation of the terrain topography, including the seabed. Having the seashore and the seabed represented by a graph, we introduce the finite element method simulations of the tsunami wave propagation. We illustrate the framework with simulations of the disastrous asteroid falling into the Baltic sea

Simulating large emitters using CMAQ and a local scale finite element model: analysis in the surroundings of Barcelona

In this work, we compare two state of the art models to simulate large emitters in the local scale. The area of study is in the surroundings of Barcelona, where an important contributor to the SO2 levels is considered. The first modelling system uses the mesoscale meteorological model WRF-ARW, the Air Emission Model of Meteosim, AEMM, and the air quality model CMAQ. The second model is a one way nesting of the results from the first system in a subgrid Finite Element model; the results from the CMAQ simulation are used as initial and boundary conditions. The simulations have been carried out for one episode with high levels of SO2. The time period of the simulations is of 48h with a 24h spin-up.Postprint (published version

Simulating large emitters using CMAQ and a local scale finite element model: analysis of the surroundings of Barcelona

In this work, we present a novel approach to simulate large emitters in the microscale. The main idea is to combine a nested grid approach and a finite element model to simulate the subgrid scale. The nested grid system consists of the mesoscale meteorological model WRF-ARW, the Air Emission Model of Meteosim (AEMM), and the air quality model CMAQ. The subgrid scale is simulated using an adaptive, Eulerian, non-steady finite element model. The results from the nested grid simulation are used as initial and boundary conditions in the subgrid model, making this approach one-way. A simulation has been carried out in the surroundings of Barcelona, where an important contributor to the sulphur dioxide levels is considered. The simulations were carried out for one episode with high levels of sulphur dioxide. The time period of the simulation was 48 hours with a 24-hour spin-up.Peer ReviewedPostprint (author's final draft

AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kβ/AKT inhibitors in PTEN-null breast cancer and can be overcome by combining with Mcl-1 inhibitors

Cancer therapeutic resistance; Target identificationResistencia terapéutica contra el cáncer; Identificación de objetivosResistència terapèutica contra el càncer; Identificació d'objectiusThe PI3K pathway is commonly activated in breast cancer, with PI3K-AKT pathway inhibitors used clinically. However, mechanisms that limit or enhance the therapeutic effects of PI3K-AKT inhibitors are poorly understood at a genome-wide level. Parallel CRISPR screens in 3 PTEN-null breast cancer cell lines identified genes mediating resistance to capivasertib (AKT inhibitor) and AZD8186 (PI3Kβ inhibitor). The dominant mechanism causing resistance is reactivated PI3K-AKT-mTOR signalling, but not other canonical signalling pathways. Deletion of TSC1/2 conferred resistance to PI3Kβi and AKTi through mTORC1. However, deletion of PIK3R2 and INPPL1 drove specific PI3Kβi resistance through AKT. Conversely deletion of PIK3CA, ERBB2, ERBB3 increased PI3Kβi sensitivity while modulation of RRAGC, LAMTOR1, LAMTOR4 increased AKTi sensitivity. Significantly, we found that Mcl-1 loss enhanced response through rapid apoptosis induction with AKTi and PI3Kβi in both sensitive and drug resistant TSC1/2 null cells. The combination effect was BAK but not BAX dependent. The Mcl-1i + PI3Kβ/AKTi combination was effective across a panel of breast cancer cell lines with PIK3CA and PTEN mutations, and delivered increased anti-tumor benefit in vivo. This study demonstrates that different resistance drivers to PI3Kβi and AKTi converge to reactivate PI3K-AKT or mTOR signalling and combined inhibition of Mcl-1 and PI3K-AKT has potential as a treatment strategy for PI3Kβi/AKTi sensitive and resistant breast tumours.This work was funded by the Wellcome Trust (WT206194) to KY and MJG and by AstraZeneca to KY, BRD, STB and JTL

Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns

Altres ajuts: L.M. is a recipient of an FPI fellowship. P.A. acknowledges the support of the Spanish Ministerio de Economía y Competitividad, the European Research Council (SysPharmAD: 614944), and the Generalitat de Catalunya. V.S. is a recipient of a Miguel Servet grant from ISCIII and receives funds from AGAUR (). The PDX program is supported by a GHD-Pink (FERO foundation) grant to V.S., A.G.-O. and M.P. received a FI-AGAUR and a Juan de la Cierva (MJCI-2015-25412) fellowship, respectively. M.S., P.R., and S.C. acknowledge the support of the NIH grants P30 CA008748, RO1CA190642, and the Breast Cancer Research Foundation. Additionally, P.R. receives funds from the Breast Cancer Alliance.Identification of actionable genomic vulnerabilities is key to precision oncology. Utilizing a large-scale drug screening in patient-derived xenografts, we uncover driver gene alteration connections, derive driver co-occurrence (DCO) networks, and relate these to drug sensitivity. Our collection of 53 drug-response predictors attains an average balanced accuracy of 58% in a cross-validation setting, rising to 66% for a subset of high-confidence predictions. We experimentally validated 12 out of 14 predictions in mice and adapted our strategy to obtain drug-response models from patients' progression-free survival data. Our strategy reveals links between oncogenic alterations, increasing the clinical impact of genomic profiling

Cervical cancer prevention and care in HIV clinics across sub-Saharan Africa: results of a facility-based survey.

INTRODUCTION To eliminate cervical cancer (CC), access to and quality of prevention and care services must be monitored, particularly for women living with HIV (WLHIV). We assessed implementation practices in HIV clinics across sub-Saharan Africa (SSA) to identify gaps in the care cascade and used aggregated patient data to populate cascades for WLHIV attending HIV clinics. METHODS Our facility-based survey was administered between November 2020 and July 2021 in 30 HIV clinics across SSA that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We performed a qualitative site-level assessment of CC prevention and care services and analysed data from routine care of WLHIV in SSA. RESULTS Human papillomavirus (HPV) vaccination was offered in 33% of sites. Referral for CC diagnosis (42%) and treatment (70%) was common, but not free at about 50% of sites. Most sites had electronic health information systems (90%), but data to inform indicators to monitor global targets for CC elimination in WLHIV were not routinely collected in these sites. Data were collected routinely in only 36% of sites that offered HPV vaccination, 33% of sites that offered cervical screening and 20% of sites that offered pre-cancer and CC treatment. CONCLUSIONS Though CC prevention and care services have long been available in some HIV clinics across SSA, patient and programme monitoring need to be improved. Countries should consider leveraging their existing health information systems and use monitoring tools provided by the World Health Organization to improve CC prevention programmes and access, and to track their progress towards the goal of eliminating CC

The number of tree species on Earth

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global groundsourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are 73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness

The number of tree species on Earth.

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global ground-sourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are ∼73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness