Evolution des propriétés des nuages opaques aux tropiques pendant le 21e siècle : impact de la dynamique atmosphérique, de la variabilité naturelle climatique et du forçage anthropique

La plus grande incertitude sur les prédictions climatiques vient de notre mauvaise compréhension de la façon dont les nuages réagiront à un climat plus chaud. Un enregistrement à long terme des détections de nuages par des capteurs actifs, tels que des lidars, permettra de mesurer la distribution verticale des nuages, l'une des propriétés les plus sensibles au réchauffement climatique. Dans cette thèse, nous regardons le futur des nuages opaques aux Tropiques en convection à l'aide de deux modèles climatiques et son observation par lidar spatial. Nous explorons, dans un premier temps, les interactions entre propriétés des nuages opaques, a priori sensibles au changement climatique, et les propriétés dynamique et thermodynamique de l'atmosphère dans les tropiques, dérivées d'observations issues d'un lidar spatial (CALIPSO-GOCCP), de réanalyses (ERA5) et de 2 modèles climatiques (CESM1 et IPSL-CM6). Les deux modèles surestiment la couverture nuageuse moyenne opaque. IPSL-CM6 met les nuages hauts opaques trop haut (+2km), surtout en ascendance. CESM1 surestime la couverture nuageuse opaque intermédiaire et sous-estime les petites et grandes couvertures nuageuses opaques. Les deux modèles s'accordent sur le fait que les propriétés des nuages se comportent différemment à une vitesse du vent supérieure (forte subsidence) ou inférieure (faible subsidence et ascendance) à +20hPa/jour. Dans le climat futur, nous constatons que les changements prédits des propriétés des nuages peuvent être déterminés au niveau régional par des changements dynamiques ou thermodynamiques, en fonction de la relation entre l'altitude des nuages opaques et ω_500 dans le modèle. Dans l'ensemble, la plupart des changements sont dus à des changements thermodynamiques dans la relation entre la propriété des nuages et la dynamique atmosphérique. Dans un second temps, nous étudions les tendances de ces propriétés des nuages opaques dans le futur et nous regardons comment les nuages opaques se comporteront lors d'événements climatiques tels que le phénomène El Niño. Nos résultats informeront les tentatives de contraindre l'évolution des nuages dans les prédictions des modèles de climat en les comparant aux observations.The largest incertitude on climate predictions comes from our poor understanding of how clouds will react to a warmer climate. A long-term record of cloud detections by active sensors, such as lidars, will enable measuring the vertical distribution of clouds, one of the properties most sensitive to global warming. In this thesis, we look at the future of opaque clouds in the tropics in convection using two climate models and its observation by spatial lidar. We first explore the interactions between the properties of opaque clouds, a priori sensitive to climate change, and the dynamic and thermodynamic properties of the atmosphere in the tropics, derived from observations from a space lidar (CALIPSO-GOCCP), reanalyses (ERA5) and climate models (CESM1 and IPSL-CM6). IPSL-CM6 puts high opaque clouds too high (+2km), especially in ascendance. CESM1 overestimates the intermediate opaque cloud cover and underestimates small and large opaque cloud covers. Both models agree that cloud properties behave differently at wind speed above (strong subsidence) or below (weak subsidence and ascendance) 20hPa/day. In the future climate, we find that predicted changes of cloud properties can be regionally driven by dynamic or thermodynamic changes, depending on the relationship between opaque cloud altitude and ω_500 in the model. Overall, most changes are due to thermodynamic changes in the relationship between cloud property and atmospheric dynamics. Secondly, we study the trends of these properties of opaque clouds in the future and we look at how opaque clouds will behave during climatic events such as the El Niño phenomenon. Our results will inform attempts to constrain cloud evolution in climate model predictions by comparing them to observations

EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor

ACKNOWLEDGEMENTS We thank J. M. Valverde (IRB) as well as the NMR facilities of the University of Barcelona (CCiT UB) and the Instituto de Química Física Rocasolano (IQFR, CSIC) for their assistance in, respectively, protein production and NMR. This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (Fellowship to E.D.M. and CancerTec grants to X.S.) MICINN (CTQ2009-08850 to X.S.), MINECO (BIO2012-31043 to X.S.; CTQ2014-56361-P to A.R), Marató de TV3 (102030 to X.S. and 102031 to E.E.P) the COFUND programme of the European Commission (C.T.W.P., A. R. and X.S.), the European Research Council (CONCERT, contract number 648201, to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.) the Serra Hunter Programme (E.E.P.) and AGAUR (SGR-2014-56RR14 to E.E.P). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)Peer reviewedPostprin

Observer based dynamic adaptive cooling system for power modules

This paper presents an advanced dynamic cooling strategy for multi-layer structured power electronic modules. An observer based feedback controller is proposed to reduce a power device or module's thermal cycle amplitude during operation, with the aim of improving reliability and lifetime. The full-state observer design is based on a developed Cauer type thermal model. The observer enables estimation and control of the temperature at reliability critical locations only measuring one accessible location. This makes the method particularly powerful and suitable for application in power systems. The designed strategy is confirmed experimentally. Although the experiment is developed for a specific application scenario, the proposed strategy is of general validity

Observer based temperature control for reduced thermal cycling in power electronic cooling

This paper presents an advanced dynamic cooling strategy for multi-layer structured power electronic modules. A observer based feedback controller is proposed to reduce a power device or module's thermal cycle amplitude during operation, with the aim of improving reliability and lifetime. The full-state observer design is based on a developed Cauer type thermal model. The observer enables estimation and control of the temperature at reliability critical locations only measuring one accessible location. This makes the method particularly powerful and suitable for application in power systems. The designed strategy is confirmed experimentally. Although the experiment is developed for a specific application scenario, the proposed strategy is of general validity

Phosphorylation-dependent differences in CXCR4-LASP1-AKT1 Interaction between breast cancer and chronic myeloid leukemia

The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes,including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptoris highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently,the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partnerand as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding ofLASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays,pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally,findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronicmyeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment

Physiology of breathlessness associated with pleural effusions

Purpose of review: Pleural effusions have a major impact on the cardiorespiratory system. This article reviews the pathophysiological effects of pleural effusions and pleural drainage, their relationship with breathlessness, and highlights key knowledge gaps. Recent findings: The basis for breathlessness in pleural effusions and relief following thoracentesis is not well understood. Many existing studies on the pathophysiology of breathlessness in pleural effusions are limited by small sample sizes, heterogeneous design and a lack of direct measurements of respiratory muscle function. Gas exchange worsens with pleural effusions and improves after thoracentesis. Improvements in ventilatory capacity and lung volumes following pleural drainage are small, and correlate poorly with the volume of fluid drained and the severity of breathlessness. Rather than lung compression, expansion of the chest wall, including displacement of the diaphragm, appears to be the principle mechanism by which the effusion is accommodated. Deflation of the thoracic cage and restoration of diaphragmatic function after thoracentesis may improve diaphragm effectiveness and efficiency, and this may be an important mechanism by which breathlessness improves. Effusions do not usually lead to major hemodynamic changes, but large effusions may cause cardiac tamponade and ventricular diastolic collapse. Patients with effusions can have impaired exercise capacity and poor sleep quality and efficiency. Summary: Pleural effusions are associated with abnormalities in gas exchange, respiratory mechanics, respiratory muscle function and hemodynamics, but the association between these abnormalities and breathlessness remains unclear. Prospective studies should aim to identify the key mechanisms of effusion-related breathlessness and predictors of improvement following pleural drainage

Kinetic analysis of the early signaling steps of the human chemokine receptor CXCR4

G protein-coupled receptors (GPCRs) are biological switches that transduce extracellular stimuli into intracellular responses in the cell. Temporally resolving GPCR transduction pathways is key to understanding how cell signaling occurs. Here, we investigate the kinetics and dynamics of the activation and early signaling steps of the chemokine receptor CXCR4 in response to its natural ligands CXCL12 and macrophage migration inhibitory factor (MIF), using Förster resonance energy transfer-based approaches. We show that CXCR4 presents a multifaceted response to CXCL12, with receptor activation (≈0.6s) followed by a rearrangement in the receptor/G protein complex (≈1s), a slower dimer rearrangement (≈1.7s) and prolonged G protein activation (≈4s). In comparison, MIF distinctly modulates every step of the transduction pathway, indicating distinct activation mechanisms and reflecting the different pharmacological properties of these two ligands. Our study also indicates that CXCR4 exhibits some degree of ligand-independent activity, a relevant feature for drug development. SIGNIFICANCE STATEMENT: The CXCL12/CXCR4 axis represents a well-established therapeutic target for cancer treatment. We demonstrate that CXCR4 exhibits a multifaceted response that involves dynamic receptor dimer rearrangements, which is kinetically embedded between receptor-G protein complex rearrangements and G protein activation. The alternative endogenous ligand MIF behaves opposite to CXCL12 in each assay studied and does not lead to G protein activation. This detailed understanding of the receptor activation may aid in the development of more specific drugs against this target

Influence of the practice setting on diagnostic prediction rules using FENO measurement in combination with clinical signs and symptoms of asthma

Objectives: To evaluate the influence of the practice setting on diagnostic accuracy of fractional exhaled nitric oxide (FENO) for diagnosing asthma; and to develop prediction rules for diagnostic decision-making including clinical signs and symptoms (CSS). Setting: Patients from 10 general practices and 1 private practice of 5 pneumologists in ambulatory care. Participants: 553 patients, 57.9% female. Consecutive inclusion of diagnostic-naive patients suspected of suffering from obstructive airway disease. Exclusion criteria were respiratory tract infections within the last 6 weeks. Interventions: The index test was FENO measurement. Reference standard was the Tiffeneau ratio (forced expiratory volume in 1 s/vital capacity) or airway resistance as assessed by whole body plethysmography, with additional bronchoprovocation or bronchodilator testing. Primary and secondary outcome measures: Asthma as determined by pneumologists, who were blind to FENO measurement results. Prediction rules were derived from multiple logistic regression analysis. A freely available calculator that allows computing all combinations was developed. Results: The practice setting only had minor influence on sensitivities of FENO cut-off points. In the final model (n=472), allergic rhinitis, wheezing and previous medication were positively associated with asthma. Increasing age and recurrent respiratory tract infections were negatively associated. The area under the curve (AUC) of FENO (AUC=0.650; 95% CI 0.599 to 0.701) increased significantly (p30 ppb. Ruling out with FENO <16 ppb in patients <43 years was only possible without allergic symptoms when recurrent respiratory tract infections were present. Conclusions: FENO results should be interpreted in the context of CSS to enhance their diagnostic value in primary care. The final diagnostic model appears as a sound algorithm fitting well to the established diagnostic rules related to CSS of asthma. FENO appears more effective for ruling in asthma than for ruling it out