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ObjectiveWe investigated the predictive value of the enzyme-linked immunospot technique (ELISPOT) in identifying patients with relapsing-remitting multiple sclerosis (RRMS) who will respond to treatment with glatiramer acetate (GA) or interferon-β (IFN-β), based on the brain-reactive B-cell activity of peripheral blood cells.MethodsIn this retrospective, cross-sectional, real-world multicenter study, we identified patients with RRMS in the NeuroTransData MS registry and stratified them based on their documented treatment response (relapse-free in the first 12 months of treatment) to GA or IFN-β. The GA group comprised 73 patients who responded to GA and 35 nonresponders. The IFN-β group comprised 62 responders to IFN-β and 37 nonresponders. Patients with previous or current therapy affecting B-cell activity were excluded. We polyclonally stimulated mononuclear cells from peripheral blood samples (collected after participant selection) and investigated brain-reactive B-cell activity after incubation on brain tissue lysate-coated ELISPOT plates. Validity metrics of the ELISPOT testing results were calculated (Python 3.6.8) in relation to the clinical responsiveness in the 2 treatment groups.ResultsThe ELISPOT B-cell activity assay showed a sensitivity of 0.74, a specificity of 0.76, a positive predictive value of 0.78, a negative predictive value of 0.28, and a diagnostic OR of 8.99 in predicting clinical response to GA vs IFN-β therapy in patients with RRMS.ConclusionMeasurement of brain-reactive B-cell activity by ELISPOT provides clinically meaningful predictive probabilities of individual patients' treatment response to GA or IFN-β. The assay has the potential to improve the selection of optimal first-line treatment for individual patients with RRMS.Classification of EvidenceThis study provides Class II evidence that in patients with RRMS, the brain reactivity of their peripheral-blood B cells predicts clinical response to GA and IFN-β.

Nowadays, small wind turbines (SWTs) are designed according to specific regulations, which ensure the safety, the maintenance, and the operation under specified external loading conditions. Wind turbine One Shot Blade® manufacturing technology has been found compliant with the IEC 61400 and the Germanischer-Lloyd (GL) regulations for the SWTs. However, in order to ensure the safety, the requirements set by the regulations, based on uncertainty regarding the damage onset and evolution during service, lead to over-dimensioned blades design not fully realising the promising benefits in terms of weight of composite materials and, hence, in terms of blade energy efficiency. In this work, the results of a preliminary study finalised to the re-design of a 10-meter long fiberglass wind turbine blade, based on One Shot Blade® manufacturing technology are introduced. Indeed, the wing turbine blade, designed according to the above-mentioned regulations, has been modified in order to meet damage tolerance requirements with the aim to reduce the weight satisfying, at the same time, the strength, durability and stiffness requirements. Advanced non-linear structural Finite Elements based analyses have been performed to verify the capability of the structure to tolerate the damage under service loading conditions, by considering damage onset and evolution. Finally, comparisons between the proposed damage tolerant One Shot Blade® and the previous designs fully compliant to regulations are reported and discussed.

Este trabalho tem por objetivo principal socializar, via relato de experiência, os reflexos sociais de uma ação de Educação Ambiental desenvolvida em uma escola estadual do município de São Carlos. A ação descrita trata de uma linha de estudo de Metodologias Ativas, com a implementação de uma horta escolar aplicada com 23 alunos do 5º ano do Ensino Fundamental, com realização no período de março a junho de 2019. A partir das atividades desenvolvidas pode-se observar o engajamento dos alunos no projeto, assim como a assimilação de conceitos de agricultura e compostagem. O desenvolvimento da horta rendeu experiências positivas no que concerne à inserção de atividades de proteção e manejo ambiental na comunidade escolar, sendo recomendada a difusão da iniciativa, por gestores e pesquisadores, no ambiente escolar. Dessa forma desenvolvimento de Metodologias Ativas utilizando aulas práticas, como a utilização de horta escolar podem representar um valioso recurso pedagógico para o fomento da Educação Ambiental em instituições formais de ensino

Atmospheric fluxes of dissolved organic matter (DOM) were studied for the first time at the Island of Lampedusa, a remote site in the Central Mediterranean Sea (Med Sea), close to the Sahara desert, between 19 March 2015 and 1 April 2017. The main goals of this work are: to quantify total atmospheric deposition of DOM in this area and to evaluate the impact of dust deposition on DOM dynamics in the surface waters of the Mediterranean Sea. Our data show high variability in DOM deposition rates without a clear seasonality and allow to estimate a dissolved organic carbon (DOC) input from the atmosphere of 120.7 mmol DOC m−2 yr−1. Over the entire time-series, the average dissolved organic phosphorous (DOP) and dissolved organic nitrogen (DON) contributions to the total dissolved pools were 40 % and 26 %, respectively. The data on atmospheric elemental ratios also show that each deposition event is characterized by a specific elemental ratio, suggesting a high variability in DOM composition and the presence of multiple sources. This study indicates that the organic substances transported by Saharan dust at Lampedusa site mainly have natural origin, especially from sea spray and that Saharan dust can be an important carrier of organic substances, even if the load of DOC associated with dust is highly variable. Our estimates suggest that atmospheric input has an impact to the Med Sea larger than to the global ocean and that DOC fluxes from the atmosphere to the Med Sea can be up to 6-fold larger than river input. Longer time series, combined with a modelling effort, are therefore mandatory in order to investigate the response of DOM dynamics in the Med Sea to the change in aerosol deposition pattern due to the effect of climate change.

DNA amplification reactions are often used for nucleic acid analysis on lab-on-chip devices. In view of point of care testing e.g. for pathogen detection in emergency stations, such an analysis must be fast and simple to be performed. As an alternative to fluorescence based measurements the method presented here is based on detecting the change in the rheological properties of the assay. For the first time, on chip DNA amplification with real time viscometric detection is shown, with first results already being available after less than 20 min. The change of the sample's viscosity during the polymerization employing the rolling circle amplification (RCA) is detected using a micromachined vibrating cantilever. The RCA was chosen, as it is isothermal and produces very long strands resulting in a high change of the fluid's rheological properties. As the reaction proceeds, an increase of the cantilever's damping and required excitation power to keep its amplitude constant is observed in real-time. Evaluating the slope of these two parameters e.g. 27 min after starting the reaction, samples where polymerization takes place and samples without reaction can perfectly be distinguished. The described approach works without explicit functionalization of the sensor surface or labeling of reaction components.

The James Webb Space Telescope (JWST) presents the opportunity to transform our understanding of planets and the origins of life by revealing the atmospheric compositions, structures, and dynamics of transiting exoplanets in unprecedented detail. However, the high-precision, time-series observations required for such investigations have unique technical challenges, and prior experience with other facilities indicates that there will be a steep learning curve when JWST becomes operational. In this paper we describe the science objectives and detailed plans of the Transiting Exoplanet Community Early Release Science (ERS) Program, which is a recently approved program for JWST observations early in Cycle 1. The goal of this project, for which the obtained data will have no exclusive access period, is to accelerate the acquisition and diffusion of technical expertise for transiting exoplanet observations with JWST, while also providing a compelling set of representative datasets that will enable immediate scientific breakthroughs. The Transiting Exoplanet Community ERS Program will exercise the time-series modes of all four JWST instruments that have been identified as the consensus highest priorities, observe the full suite of transiting planet characterization geometries (transits, eclipses, and phase curves), and target planets with host stars that span an illustrative range of brightnesses. The observations in this program were defined through an inclusive and transparent process that had participation from JWST instrument experts and international leaders in transiting exoplanet studies. Community engagement in the project will be centered on a two-phase Data Challenge that culminates with the delivery of planetary spectra, time-series instrument performance reports, and open-source data analysis toolkits in time to inform the agenda for Cycle 2 of the JWST mission.

Detailed atmospheric and aerosol properties, and radiation measurements were carried out in summer 2013 during the Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region (ADRIMED) campaign in the framework of the Chemistry-Aerosol Mediterranean Experiment (ChArMEx) experiment. This study focusses on the characterization of infrared (IR) optical properties and direct radiative effects of mineral dust, based on three vertical profiles of atmospheric and aerosol properties and IR broadband and narrowband radiation from airborne measurements, made in conjunction with radiosonde and ground-based observations at Lampedusa, in the central Mediterranean. Satellite IR spectra from IASI are also included in the analysis. The atmospheric and aerosol properties are used as input to a radiative transfer model, and various IR radiation parameters (upward and downward irradiance, nadir and zenith brightness temperature at different altitudes) are calculated and compared with observations. The model calculations are made for different sets of dust size distribution and refractive indices, derived from observations and from the literature. The main results of the analysis are that the IR dust radiative forcing is non negligible, and strongly depends on size distribution (SD) and refractive index (RI). When calculations are made using the in situ measured size distribution, it is possible to identify the refractive index that produces the best match with observed IR irradiances and brightness temperatures (BTs). The most appropriate refractive indices correspond to those determined from independent measurements of mineral dust aerosols from the source regions (Tunisia, Algeria, Morocco) of dust transported over Lampedusa, suggesting that differences in the source properties should be taken into account. With the in situ size distribution and the most appropriate refractive index the estimated dust IR radiative forcing efficiency is +23.7 W m-2 at the surface, -7.9 W m-2 within the atmosphere, and +15.8 W m-2 at the top of the atmosphere. The use of column integrated dust SD from AERONET may also produce a good agreement with measured irradiances and BTs, but with significantly different values of the RI. This implies large differences, up to a factor of 2.5 at surface, in the estimated dust radiative forcing, and in the IR heating rate. This study shows that spectrally resolved measurements of brightness temperatures are important to better constrain the dust IR optical properties, and to obtain a reliable estimate of its radiative effects. Efforts should be directed at obtaining an improved description of the dust size distribution, its vertical distribution, and at including regionally-resolved optical properties.

El agua subterránea es la única fuente de abastecimiento para la población y soporte esencial de las diversas actividades que se desarrollan en el sudeste de la provincia de Buenos Aires; constituye, además, un insumo esencial en los servicios ecológicos de los ecosistemas. El objetivo del trabajo fue generar una priorización de subcuencas hidrológicas para la gestión de los recursos hídricos subterráneos a través de un modelo multicriterio que pueda ser utilizado como herramienta de prevención y planificación del mismo. A partir del análisis de la red de drenajes en la zona mediante el modelo Soil and Water Assessment Tool (SWAT) se delimitaron siete subcuencas de interés. Dichas subcuencas se tomaron como alternativas del modelo de decisión Simple Multi-Attribute Rating Technique (SMART) utilizando el software Criterium Decision Plus (CDP). Se definieron tres criterios de decisión: ubicación de las potenciales fuentes puntuales de contaminación; ubicación de los pozos públicos de extracción de agua para consumo humano y; profundidad del agua subterránea. Los resultados obtenidos destacan dos de las subcuencas estudiadas como las de mayor prioridad, las cuales presentan numerosas fuentes puntuales de potencial contaminación y pozos de extracción de agua para consumo humano. Eje temático: Legislación del Agua, Planificación y Economía de agua

Background MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). Methods MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P1 receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. Results FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220+ B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. Conclusions The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE. Electronic supplementary material The online version of this article (doi:10.1186/s12974-017-0924-4) contains supplementary material, which is available to authorized users.

Tumor-derived vesicles (TDV) have been recently implicated in immunosuppression by transporting specific proteins, including Fas ligand (FasL) and TRAIL, to immune cells. We hypothesized that TDVs carrying miRNAs with immunological function could interfere with the translational machinery of immune cells and lead to TDV-mediated immunosuppression in cancer. We show that TDVs from human tumor cells indeed contain multiple miRNA species with known roles in lymphocyte development and function: hsa-miR-146a, miR-29a, and miR-21. Quantification by RT-PCR shows that the amount of miR-21 within TDVs isolated from the breast cancer cell line HCC1806 is at physiologically relevant levels. Additionally, we show that these miRNAs carried by TDVs copurify with argonaute proteins. This observation corroborates the idea that the machinery of microvesicle secretion and that of RNA interference are interconnected.