Towards a regional ocean forecasting system for the IBI (Iberia-Biscay-Ireland area): developments and improvements within the ECOOP project framework

The regional ocean operational system remains a key element in downscaling from large scale (global or basin scale) systems to coastal ones. It enables the transition between systems in which the resolution and the resolved physics are quite different. Indeed, coastal applications need a system to predict local high frequency events (inferior to the day) such as storm surges, while deep sea applications need a system to predict large scale lower frequency ocean features. In the framework of the ECOOP project, a regional system for the Iberia-Biscay-Ireland area has been upgraded from an existing V0 version to a V2. This paper focuses on the improvements from the V1 system, for which the physics are close to a large scale basin system, to the V2 for which the physics are more adapted to shelf and coastal issues. Strong developments such as higher regional physics resolution in the NEMO Ocean General Circulation Model for tides, non linear free surface and adapted vertical mixing schemes among others have been implemented in the V2 version. Thus, regional thermal fronts due to tidal mixing now appear in the latest version solution and are quite well positioned. Moreover, simulation of the stratification in shelf areas is also improved in the V2

Development and evaluation of the Walking Estimated-Limitation Calculated by History questionnaire in patients with claudication

BACKGROUND: The Walking Impairment Questionnaire (WIQ) is used to estimate walking impairment in patients with peripheral artery disease; however, it faces frequent errors when self-completed and is complex to score. We aimed to validate an alternative, easily scored four-item tool, the Walking Estimated-Limitation Calculated by History (WELCH) questionnaire. METHODS: The WIQ and WELCH were prospectively tested in five centers. We studied 434 patients, among which 298 had a treadmill test (3.2 km/h; 10% slope) to determine their maximum walking time (MWT), and 30 were seen twice during the study period. RESULTS: After self-completion, we found at least one error in 177 WIQ (40.8%; 95% confidence interval [CI], 36.3%-45.5%) vs 56 WELCH (12.9%; 95% CI, 10.1%-16.4%) questionnaires (P < .0001). When scoring only questionnaires without missing or duplicate answers, 267 WIQ (61.5%; 95% CI, 56.9%-66.0%) vs 393 WELCH (90.6%; 95% CI, 87.4%-93.0%) questionnaires could be scored (P < .001). The median MWT was 233 seconds (interquartile range, 133-654 seconds) for the 298 patients who had a treadmill test. When the 296 patients who had both questionnaire scores available were studied, no difference was found between the Pearson r coefficient of correlation of the WIQ (r = 0.615) and the WELCH (r = 0.653) with MWT (P = .211). In the 30 patients who completed the WELCH twice, correlation was r = 0.839 (P < .001) between the two scores in 22 nonrevascularized patients, and the area under the receiver-operating characteristic curve was 0.830 +/- 0.105 (P < .01) to discriminate the eight revascularized from the 22 nonrevascularized patients. CONCLUSIONS: The WELCH questionnaire is a simple tool to estimate walking limitation in patients with suspected peripheral artery disease. It is easily scored by mental calculation. It may help to standardize the estimation of walking limitation in routine clinical practice

The Hrs/Stam Complex Acts as a Positive and Negative Regulator of RTK Signaling during Drosophila Development

BACKGROUND: Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK) signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. PRINCIPAL FINDINGS: Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. CONCLUSIONS/SIGNIFICANCE: Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development

Automated terrestrial laser scanning with near-real-time change detection – monitoring of the Séchilienne landslide

We present an automated terrestrial laser scanning (ATLS) system with automatic near-real-time change detection processing. The ATLS system was tested on the Séchilienne landslide in France for a 6-week period with data collected at 30min intervals. The purpose of developing the system was to fill the gap of high-temporal-resolution TLS monitoring studies of earth surface processes and to offer a cost-effective, light, portable alternative to ground-based interferometric synthetic aperture radar (GB-InSAR) deformation monitoring. During the study, we detected the flux of talus, displacement of the landslide and pre-failure deformation of discrete rockfall events. Additionally, we found the ATLS system to be an effective tool in monitoring landslide and rockfall processes despite missing points due to poor atmospheric conditions or rainfall. Furthermore, such a system has the potential to help us better understand a wide variety of slope processes at high levels of temporal detail

Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for \u3b2-Thalassemia

Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess the benefit-to-risk ratio. To support the clinical development of gene therapy for \u3b2-thalassemia, we performed in vitro and in vivo studies for prediction of safety. First we developed newly GLOBE-derived vectors that were tested for their transcriptional activity and potential interference with the expression of surrounding genes. Because these vectors did not show significant advantages, GLOBE lentiviral vector (LV) was elected for further safety characterization. To support the use of hematopoietic stem cells (HSCs) transduced by GLOBE LV for the treatment of \u3b2-thalassemia, we conducted toxicology, tumorigenicity, and biodistribution studies in compliance with the OECD Principles of Good Laboratory Practice. We demonstrated a lack of toxicity and tumorigenic potential associated with GLOBE LV-transduced cells. Vector integration site (IS) studies demonstrated that both murine and human transduced HSCs retain self-renewal capacity and generate new blood cell progeny in the absence of clonal dominance. Moreover, IS analysis showed an absence of enrichment in cancer-related genes, and the genes targeted by GLOBE LV in human HSCs are well known sites of integration, as seen in other lentiviral gene therapy trials, and have not been associated with clonal expansion. Taken together, these integrated studies provide safety data supporting the clinical application of GLOBE-mediated gene therapy for \u3b2-thalassemia

Using street view imagery for 3-D survey of rock slope failures

We discuss here different challenges and limitations of surveying rock slope failures using 3-D reconstruction from image sets acquired from street view imagery (SVI). We show how rock slope surveying can be performed using two or more image sets using online imagery with photographs from the same site but acquired at different instances. Three sites in the French alps were selected as pilot study areas: (1) a cliff beside a road where a protective wall collapsed, consisting of two image sets (60 and 50 images in each set) captured within a 6-year time frame; (2) a large-scale active landslide located on a slope at 250m from the road, using seven image sets (50 to 80 images per set) from five different time periods with three image sets for one period; (3) a cliff over a tunnel which has collapsed, using two image sets captured in a 4-year time frame. The analysis include the use of different structure from motion (SfM) programs and a comparison between the extracted photogrammetric point clouds and a lidar-derived mesh that was used as a ground truth. Results show that both landslide deformation and estimation of fallen volumes were clearly identified in the different point clouds. Results are site- and software-dependent, as a function of the image set and number of images, with model accuracies ranging between 0.2 and 3.8m in the best and worst scenario, respectively. Although some limitations derived from the generation of 3-D models from SVI were observed, this approach allowed us to obtain preliminary 3-D models of an area without on-field images, allowing extraction of the pre-failure topography that would not be available otherwise

An integrated analysis of surface velocities induced by rainfall in the Séchilienne landslide (Western Alps, France)

International audienceAn integrated analysis on the relationship between rainfall and displacement in the most active area of the Séchilienne unstable slope was performed. This study combines several techniques and models to adequately reproduce the landslide movement induced by the rainfall. The analysis of available time series shows a long term trend and seasonal variations in the displacement, respectively independent and synchronous to precipitations. In particular wavelet analysis highlights that the movement is rather linked to groundwater recharge than to precipitation (rainfall + snowfall), involving then the importance of groundwater process in the area. A first and simple relationship between the water input and the fluctuations of displacements apart from the general trend is shown using a tank model. Moreover, a seasonal analysis of this relationship was performed, showing that displacement rate follows the behavior of the hydrological cycle. Two different models were applied to the long temporal series of extensometric and precipitation data: the FLAME model, from BRGM and the FORESEES model, from Univ. Lausanne. These tools are based on a combined statistical-mechanical approach to predict changes in landslide displacement rates from observed changes in precipitation amounts. The forecasting tool FLAME associates 1) a statistical impulse response (IR) model to simulate the changes in landslide rates by computing a transfer function between the rainfall and the displacements, and 2) a 1D mechanical (ME) model (e.g. visco-plastic rheology), in order to take into account changes in pore water pressures. The performance of different combinations of models was evaluated against observed displacement rates at the selected pilot study area. Our results indicate that both models are able to reproduce, with a high degree of accuracy, the observed displacement pattern in the general kinematic regime. Finally the variability of the results, depending in particular on the input data, is discussed

Eddy-Permitting Ocean Circulation Hindcasts of Past Decades

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