6,062 research outputs found

    Quantifying how user-interaction can modify the perception of the value of climate information: A Bayesian approach

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    ArticleThis is the final version of the article. Available from Elsevier via the DOI in this record.The growing attention user relevance is receiving in the context of climate services is giving new light to engagement activities. However, while there is an almost unanimous consensus that these are important to the delivery of usable services, there is relatively little quantitative evidence of their impact on the usefulness of the service or its value as perceived by the users and decision-makers. Using a simple Bayesian decision theoretic framework, we have analysed how the perceived value of the service changes as a function of the user’s belief in the accuracy of the forecast. Based on this, we conclude, that, at least for the generic users adopted for our analysis, 30 or more repeated forecasts may be needed to ascertain the real user value of a predictive service. However, we argue that engagement between users and service providers can play a significant role in modifying the perceived accuracy and value of the service, bringing it closer in line with the objective evaluation. This requires feedback from users on both the specific climate information content and its presentation, alongside exploring the user’s attitude to risk. If appropriate engagement can be achieved, this work suggests that it has the potential to alter the overall perceived cost-benefit ratio over a relatively short period of time, enabling users to make best use of the available climate information.This work was supported by the Joint DECC/Defra Met Office Hadley Centre Climate Programme (GA01101). The authors wish to acknowledge all of those who contributed indirectly to the development of the EUPORIAS winter transport prototype (Seasonal Prototype: Risk of Impacts from NAO on Transport; http://sprint.euporias.eu/), through scientific discussion, review, data provision, stakeholder engagement and facilitation: Erika Palin, Adam Scaife, Anca Brookshaw, Alberto Arribas, and the UK Department for Transport-led stakeholder group. The UK Government Department for Transport is acknowledged for providing financial support, in parallel to that received from EUPORIAS, for the SPRINT prototype. EUPORIAS was funded by the European Commission through the 7th Framework Programme for Research, grant agreement 308291

    Exploring constraints on the realised value of a forecast-based climate service

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    This is the final version, also available from Elsevier via the DOI in this record.The increasingly widespread use of climate services for decision-making has highlighted the need for service developers to more clearly establish the benefits and limitations of the information they provide. Using a simple cost/loss framework applied to an idealised forecast system, we explore the critical level of accuracy required for the expected utility of a predictive service to exceed a benchmark based on the climatological frequency of the hazard. In this simplest case, the critical accuracy is a function only of the cost/loss ratio for the decision and the climatological frequency. Although the utility of climate services depends on a number of non-climate-related factors, comparing current forecasting capabilities to an estimate of the critical accuracy can provide a guide to the expected marginal benefit of the climate service. More generally, to ensure that climate service evaluation is relevant to users it must account for the finite duration over which a climate service is used, since the realised performance can differ significantly from its expectation. Here, the statistical distribution of realised performance is used to quantify the prior likelihood that the service will outperform a benchmark as a function of accuracy, climatological frequency, cost/loss ratio and duration of usage. This information can help users assess the potential risks associated with adopting a climate service for a given period, and may help identify geographical regions and meteorological parameters for which a forecasting tool could provide a worthwhile investment with respect to the next-best alternative.Met Office Hadley Centre Climate Programm

    A spectroscopic cell for fast pressure jumps across the glass transition line

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    We present a new experimental protocol for the spectroscopic study of the dynamics of glasses in the aging regime induced by sudden pressure jumps (crunches) across the glass transition line. The sample, initially in the liquid state, is suddenly brought in the glassy state, and therefore out of equilibrium, in a four-window optical crunch cell which is able to perform pressure jumps of 3 kbar in a time interval of ~10 ms. The main advantages of this setup with respect to previous pressure-jump systems is that the pressure jump is induced through a pressure transmitting fluid mechanically coupled to the sample stage through a deformable membrane, thus avoiding any flow of the sample itself in the pressure network and allowing to deal with highly viscous materials. The dynamics of the sample during the aging regime is investigated by Brillouin Light Scattering (BLS). For this purpose the crunch cell is used in conjunction with a high resolution double monochromator equipped with a CCD detector. This system is able to record a full spectrum of a typical glass forming material in a single 1 s shot. As an example we present the study of the evolution toward equilibrium of the infinite frequency longitudinal elastic modulus (M_infinity) of a low molecular weight polymer (Poly(bisphenol A-co-epichlorohydrin), glycidyl end capped). The observed time evolution of M_infinity, well represented by a single stretched exponential, is interpreted within the framework of the Tool-Narayanaswamy theory.Comment: 9 pages, 11 figure

    Morphology of the tropopause layer and lower stratosphere above a tropical cyclone : a case study on cyclone Davina (1999)

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    During the APE-THESEO mission in the Indian Ocean the Myasishchev Design Bureau stratospheric research aircraft M55 Geophysica performed a flight over and within the inner core region of tropical cyclone Davina. Measurements of total water, water vapour, temperature, aerosol backscattering, ozone and tracers were made and are discussed here in comparison with the averages of those quantities acquired during the campaign time frame. Temperature anomalies in the tropical tropopause layer (TTL), warmer than average in the lower part and colder than average in the upper TTL were observed. Ozone was strongly reduced compared to its average value, and thick cirrus decks were present up to the cold point, sometimes topped by a layer of very dry air. Evidence for meridional transport of trace gases in the stratosphere above the cyclone was observed and perturbed water distribution in the TTL was documented. The paper discuss possible processes of dehydration induced by the cirrus forming above the cyclone, and change in the chemical tracer and water distribution in the lower stratosphere 400–430 K due to meridional transport from the mid-latitudes and link with Davina. Moreover it compares the data prior and after the cyclone passage to discuss its actual impact on the atmospheric chemistry and thermodynamics

    Optical measurements of atmospheric particles from airborne platforms: in situ and remote sensing instruments for balloons and aircrafts

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    Multiwavelength laser backscattersondes (MAS) have been widely used from a variety of airborne platforms for in situ measurements of optical properties of clouds and atmospheric particulate as well as their phase and composition. Recently, a new miniaturized LIDAR (MULID) has been developed using state-of-art technology for balloon borne profiling of the same quantities. A description of the two instruments, a survey of preliminary results obtained during test flights and indications for future use are given

    Therapeutic targeting of CK2 in acute and chronic leukemias

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    CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosis. High levels of CK2 messenger RNA and protein are associated with CK2 pathological functions in human cancers. Over the last decade, basic and translational studies have provided evidence of CK2 as a pivotal molecule driving the growth of different blood malignancies. CK2 overexpression has been demonstrated in nearly all the types of hematological cancers, including acute and chronic leukemias, where CK2 is a key regulator of signaling networks critical for cell proliferation, survival and drug resistance. The findings that emerged from these studies suggest that CK2 could be a valuable therapeutic target in leukemias and supported the initiation of clinical trials using CK2 antagonists. In this review, we summarize the recent advances on the understanding of the signaling pathways involved in CK2 inhibition-mediated effects with a particular emphasis on the combinatorial use of CK2 inhibitors as novel therapeutic strategies for treating both acute and chronic leukemia patients

    Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies

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    Sphingolipids, such as ceramide, sphingosine and sphingosine 1-phosphate (S1P) are bioactive molecules that have important functions in a variety of cellular processes, which include proliferation, survival, differentiation and cellular responses to stress. Sphingolipids have a major impact on the determination of cell fate by contributing to either cell survival or death. Although ceramide and sphingosine are usually considered to induce cell death, S1P promotes survival of cells. Sphingosine kinases (SPHKs) are the enzymes that catalyze the conversion of sphingosine to S1P. There are two isoforms, SPHK1 and SPHK2, which are encoded by different genes. SPHK1 has recently been implicated in contributing to cell transformation, tumor angiogenesis and metastatic spread, as well as cancer cell multidrug-resistance. More recent findings suggest that SPHK2 also has a role in cancer progression. This review is an overview of our understanding of the role of SPHKs and S1P in hematopoietic malignancies and provides information on the current status of SPHK inhibitors with respect to their therapeutic potential in the treatment of haematological cancers

    The contribution of Citizens’ Observatories to validation of satellite‐retrieved soil moisture products

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    The GROW Observatory (GROW) will create a sustainable citizen platform and community to generate, share and utilise information on land, soil and water resources at a resolution hitherto not previously considered. The European Space Agency’s Sentinel‐1 is the first mission capable of providing high‐resolution soil moisture information, but a proper validation of Sentinel data remains a challenge given the scarcity of available in situ reference measurements. Establishment of a dense network of in situ measurement can bridge the gap in spatial resolution between in situ and satellite‐based soil moisture measurements enabling validation and calibration of ground and remotely measured soil moisture observations. The potential exists to answer scientific questions including the validity of satellite data, the impact of climate change on land management thus supporting the needs of growers and integrating citizen and scientific research to be more directly applicable and relevant

    Improving nelarabine efficacy in T cell acute lymphoblastic leukemia by targeting aberrant PI3K/AKT/mTOR signaling pathway

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    Background: Although in recent years, the introduction of novel chemotherapy protocols has improved the outcome of T cell acute lymphoblastic leukemia (T-ALL) patients, refractory and/or relapsing disease remains a foremost concern. In this context, a major contribution was provided by the introduction of the nucleoside analog nelarabine, approved for salvage treatment of T-ALL patients with refractory/relapsed disease. However, nelarabine could induce a life-threatening, dose-dependent neurotoxicity. To improve nelarabine efficacy, we have analyzed its molecular targets, testing selective inhibitors of such targets in combination with nelarabine. Methods: The effectiveness of nelarabine as single agent or in combination with PI3K, Bcl2, and MEK inhibitors was evaluated on human T-ALL cell lines and primary T-ALL refractory/relapsed lymphoblasts. The efficacy of signal modulators in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed by flow cytometry, western blotting, and quantitative real-time PCR in T-ALL settings. Results: Treatment with nelarabine as a single agent identified two groups of T-ALL cell lines, one sensitive and one resistant to the drug. Whereas sensitive T-ALL cells showed a significant increase of apoptosis and a strong down-modulation of PI3K signaling, resistant T-ALL cells showed a hyperactivation of AKT and MEK/ERK1/2 signaling pathways, not caused by differences in the expression of nelarabine transporters or metabolic activators. We then studied the combination of nelarabine with the PI3K inhibitors (both pan and dual γ/δ inhibitors), with the Bcl2 specific inhibitor ABT199, and with the MEK inhibitor trametinib on both T-ALL cell lines and patient samples at relapse, which displayed constitutive activation of PI3K signaling and resistance to nelarabine alone. The combination with the pan PI3K inhibitor ZSTK-474 was the most effective in inhibiting the growth of T-ALL cells and was synergistic in decreasing cell survival and inducing apoptosis in nelarabine-resistant T-ALL cells. The drug combination caused AKT dephosphorylation and a downregulation of Bcl2, while nelarabine alone induced an increase in p-AKT and Bcl2 signaling in the resistant T-ALL cells and relapsed patient samples. Conclusions: These findings indicate that nelarabine in combination with PI3K inhibitors may be a promising therapeutic strategy for the treatment of T-ALL relapsed patients
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