Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits

Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5–mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Evolution des principes de la commutation assistée dans les onduleurs de tension. Présentation d'un onduleur haute fréquence à « commutations douces »

This paper deals with a study about an inverter whose structure use the « resonant switch » concept. After having reminded the different switching modes commonly used among the voltage inverters, we suggest a converter whose performances provide a high frequency rate pulse width modulation operation. The choice of a particular control mode allows to take advantage of the features. The tests results of a 4 kW inverter using insulated gate bipolar transistors display the real qualities of the structure, particulary about dynamic performances and efficiency.Cet article a pour objet l'étude d'un onduleur dont la structure est basée sur l'utilisation d'interrupteurs dit « résonnants ». Après avoir rappelé les différents modes de commutations utilisés au sein des onduleurs de tension et souligné les similitudes structurelles des différentes solutions, nous proposons un convertisseur dont les performances autorisent un fonctionnement en modulation de largeur d'impulsion à haute fréquence. Le choix d'un mode de commande particulier permet d'en exploiter totalement les caractéristiques. L'expérimentation d'un onduleur de 4 kW, utilisant des transistors à grille isolée (I.G.B.T.) met en évidence les qualités de l'ensemble, tant sur le plan des performances dynamiques que du rendement

β-D-glucan hydrolase activities in pure cell-wall-enriched fractions from <i>Valerianella olitoria</i> cells.

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Wall-bound 1,3-β-D-glucan : orthophosphate glucosyltransferase activity from <i>Acacia</i> cultured cells

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A wall-bound exo-1,3-β-D-glucanase from <i>Acacia</i> cultured cells

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Purification of cell-wall β-D-xylanases from <i>Acacia</i> suspended cells

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MLJ: A Julia package for composable machine learning

MLJ (Machine Learing in Julia) is an open source software package providing a common interface for interacting with machine learning models written in Julia and other languages. It provides tools and meta-algorithms for selecting, tuning, evaluating, composing and comparing those models, with a focus on flexible model composition. In this design overview we detail chief novelties of the framework, together with the clear benefits of Julia over the dominant multi-language alternatives.MLJ (Machine Learing in Julia) is an open source software package providing a common interface for interacting with machine learning models written in Julia and other languages. It provides tools and meta-algorithms for selecting, tuning, evaluating, composing and comparing those models, with a focus on flexible model composition. In this design overview we detail chief novelties of the framework, together with the clear benefits of Julia over the dominant multi-language alternatives.0.14.

Xyloglucan octasaccharide XXLGol derived from the seeds of Hymenaea courbaril acts as signaling molecules

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Xyloglucan octasaccharide XXLGol derived from the seeds of Hymenaea courbaril acts as signaling molecules

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