FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination.

BackgroundFTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease.MethodsMice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice.ResultsAdministration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation.ConclusionThese findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model

How to promote innovation and interdisciplinarity in organic food and farming research evaluation

The development of organic food and farming research calls for system-oriented, innovative, interdisciplinary approaches. The process of evaluating research proposals is a crucial step towards this objective. Based on the EU CORE Organic pilot call for joint transnational research projects, we analysed to what extent the evaluation criteria and procedures implemented address this issue. Feedback on the experience of the target groups involved in this call was gathered and discussed in relation to findings from the literature. Our results show that interdisciplinary and innovative aspects could be better addressed, and evaluation criteria more clearly defined and delimited. This entails reshaping the main criteria and developing more suitable evaluation categories and sub-criteria. We also suggest creating mechanisms to enable funding of a few “risky” research projects, to facilitate entry of newcomers to the arena, to promote exploratory research projects and to support longitudinal interaction among applicants and assessors

Improving Forecast Accuracy by Guided Manual Overwrite in Forecast Debiasing

We present ongoing work on a model-driven decision support system (DSS) that is aimed at providing guidance on reflecting and adjusting judgmental forecasts. We consider judgmental forecasts of cash flows generated by local experts in numerous subsidiaries of an international corporation. Forecasts are generated in a decentralized, non-standardized fashion, and corporate managers and controllers then aggregate the forecasts to derive consolidated, corporate-wide plans to manage liquidity and foreign exchange risk. However, it is well-known that judgmental predictions are often biased, where then statistical debiasing techniques can be applied to improve forecast accuracy. Even though debiasing can improve average forecast accuracy, many originally appropriate forecasts may be automatically corrected in the wrong direction, for instance, in cases where a forecaster might have considered knowledge on future events not derivable statistically from past time series. To prevent high-impact erroneous corrections, we propose to prompt a forecaster for action upon submission of a forecast that is out of the confidence bounds of a benchmark forecast. The benchmark forecast is derived from a statistical debiasing model that considers the past error patterns of a forecaster. Bounds correspond to percentiles of the error distribution of the debiased forecast. We discuss the determination of the confidence bounds and the selection of suspicious judgmental forecasts, types of (statistical) feedback to the forecasters, and the incorporation of the forecaster’s reactions (comments, revisions) in future debiasing strategies

Influence of Post-Welding Heat Treatment on the Corrosion Behavior of a 2050-T3 Aluminum-Copper-Lithium Alloy Friction Stir Welding Joint

The corrosion behavior of a Friction Stir Welding joint in 2050-T3 Al-Cu-Li alloy was studied in 1 M NaCl solution and the influence of T8 post-welding heat treatment on its corrosion susceptibility was analyzed. After exposure to 1 M NaCl solution, the heat affected zone (HAZ) of the weld without post-welding heat treatment was found to be the most extensively corroded zone with extended intergranular corrosion damage while, following T8 post-welding heat treatment, no intergranular corrosion was observed in the HAZ and the global corrosion behavior of the weld was significantly improved. The corrosion damage observed on the welded joints after immersion in 1 M NaCl solution was compared to that obtained after 750 h Mastmaasis Wet Bottom tests. The same corrosion damage was observed. Various stationary electrochemical tests were carried out on the global welded joint and/or each of the metallurgical zones of the welded joint to understand the corrosion damage observed. TEM observations helped in bringing meaningful elements to analyze the intrinsic electrochemical behavior of the different zones of the weld related to their microstructure. However, galvanic coupling tests showed that galvanic coupling effects between the different zones of the weld were at least partially responsible for its corrosion behavior

Validation of three satellite-derived databases of surface solar radiation using measurements performed at 42 stations in Brazil

International audienceThe SoDa website (www.soda-pro.com) is populated with numerous solar-related Web services. Among them, three satellite-derived irradiation databases can be manually or automatically accessed to retrieve radiation values within the geographical coverage of the Meteosat Second Generation (MSG) satellite: the two most advanced versions of the HelioClim-3 database (versions 4 and 5, respectively HC3v4 and HC3v5), and the CAMS radiation service. So far, these databases have been validated against measurements of several stations in Europe and North Africa only. As the quality of such databases depends on the geographical regions and the climates, this paper extends this validation campaign and proposes an extensive comparison on Brazil and global irradiation received on a horizontal surface. Eleven stations from the Brazilian Institute of Space Research (INPE) network offer 1 min observations, and thirty-one stations from the Instituto Nacional de Meteorologia (INMET) network offer hourly observations. The satellite-derived estimates have been compared to the corresponding observations on hourly, daily and monthly basis. The bias relative to the mean of the measurements for HC3v5 is mostly comprised between 1 and 3 %, and that for HC3v4 between 2 and 5 %. These are very satisfactory results and they demonstrate that HC3v5, and to a lesser extent HC3v4, may be used in studies of long-term changes in SSI in Brazil. The situation is not so good with CAMS radiation service for which the relative bias is mostly comprised between 5 and 10 %. For hourly irradiation, the relative RMSE ranges from 15 to 33 %. The correlation coefficient is very large for all stations and the three databases, with an average of 0.96. The three databases reproduce well the hour from hour changes in SSI. The errors show a tendency to increase with the viewing angle of the MSG satellite. They are greater in tropical areas where the relative humidity in the atmosphere is important. It is concluded that except for the overestimation by CAMS radiation service, the three databases are suitable for studies of the solar resources in Brazil

Interrogating Seyferts with NebulaBayes: Spatially probing the narrow-line region radiation fields and chemical abundances

NebulaBayes is a new Bayesian code that implements a general method of comparing observed emission-line fluxes to photoionization model grids. The code enables us to extract robust, spatially resolved measurements of abundances in the extended narrow line regions (ENLRs) produced by Active Galactic Nuclei (AGN). We observe near-constant ionization parameters but steeply radially-declining pressures, which together imply that radiation pressure regulates the ENLR density structure on large scales. Our sample includes four `pure Seyfert' galaxies from the S7 survey that have extensive ENLRs. NGC2992 shows steep metallicity gradients from the nucleus into the ionization cones. An {\it inverse} metallicity gradient is observed in ESO138-G01, which we attribute to a recent gas inflow or minor merger. A uniformly high metallicity and hard ionizing continuum are inferred across the ENLR of Mrk573. Our analysis of IC5063 is likely affected by contamination from shock excitation, which appears to soften the inferred ionizing spectrum. The peak of the ionizing continuum E_peak is determined by the nuclear spectrum and the absorbing column between the nucleus and the ionized nebula. We cannot separate variation in this intrinsic E_peak from the effects of shock or HII region contamination, but E_peak measurements nevertheless give insights into ENLR excitation. We demonstrate the general applicability of NebulaBayes by analyzing a nuclear spectrum from the non-active galaxy NGC4691 using a HII region grid. The NLR and HII region model grids are provided with NebulaBayes for use by the astronomical community.Comment: Accepted for publication in ApJ; 29 pages with 10 figures and 3 table

MOON: Assisting Students in Completing Educational Notebook Scenarios

Jupyter notebooks are increasingly being adopted by teachers to deliver interactive practical sessions to their students. Notebooks come with many attractive features, such as the ability to combine textual explanations, multimedia content, and executable code alongside a flexible execution model which encourages experimentation and exploration. However, this execution model can quickly become an issue when students do not follow the intended execution order of the teacher, leading to errors or misleading results that hinder their learning. To counter this adverse effect, teachers usually write detailed instructions about how students are expected to use the notebooks. Yet, the use of digital media is known to decrease reading efficiency and compliance with written instructions, resulting in frequent notebook misuse and students getting lost during practical sessions. In this article, we present a novel approach, MOON, designed to remedy this problem. The central idea is to provide teachers with a language that enables them to formalize the expected usage of their notebooks in the form of a script and to interpret this script to guide students with visual indications in real time while they interact with the notebooks. We evaluate our approach using a randomized controlled experiment involving 21 students, which shows that MOON helps students comply better with the intended scenario without hindering their ability to progress. Our follow-up user study shows that about 75% of the surveyed students perceived MOON as rather useful or very useful

The Solar Forecast Similarity Method: a new method to compute solar radiation forecasts for the next day

International audienceThe need for PV plant owners to plan what they are injecting in the electricity grid is more and more stringent to avoid endangering the whole supply in electricity. A new solar forecast algorithm, named Solar Forecast Similarity Method, has been developed to predict irradiance for the next day based on a statistical study of the long term HelioClim-3 irradiation database. This algorithm searches in the past for the most similar days compared to the day of interest and uses their following days to produce a forecast. The model has been optimized against the database itself to compute the most adequate set of parameters over France and for the month of January 2014. With this configuration, the results are a null bias and a root mean square error of 48%. The algorithm outperforms the persistence by 20% and the error is similar to existing methods. An objective validation has then been carried out to compare the irradiance forecasts to high quality measurements from several Baseline Surface Radiation Network (BSRN) ground stations. The method is very promising since the comparison results are in line or lower than the one obtained with the first validation analysis performed on the HelioClim-3 database. For high frequencies, however, predictions have a high error for rapidly varying weather. This demonstrates that the method provides information for the averaged production the following day but requires another input to reliably predict high frequency irradiance