The Genetic Signature of Perineuronal Oligodendrocytes

Oligodendrocytes in the central nervous system can be categorized as precursors, myelin-forming, and non-myelinating perineuronal cells. The function of perineuronal oligodendrocytes is unknown; it was proposed that following injury, they may remyelinate denuded axons. We investigated these cells' potential. A combination of cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As cells that embrace neuronal somata, they integrate a repertoire of transcripts designed to create their own code for communicating with neurons. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for - we speculate - a demyelinating episode. We posit that the signature molecules, PDGFR-[alpha][beta] cytokine PDGF-CC, and transcription factor Pea3, used - among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of an elusive neural cell

A cloud-agnostic queuing system to support the implementation of deadline-based application execution policies

There are many scientific and commercial applications that require the execution of a large number of independent jobs resulting in significant overall execution time. Therefore, such applications typically require distributed computing infrastructures and science gateways to run efficiently and to be easily accessible for end-users. Optimising the execution of such applications in a cloud computing environment by keeping resource utilisation at minimum but still completing the experiment by a set deadline has paramount importance. As container-based technologies are becoming more widespread, support for job-queuing and auto-scaling in such environments is becoming important. Current container management technologies, such as Docker Swarm or Kubernetes, while provide auto-scaling based on resource consumption, do not support job queuing and deadline-based execution policies directly. This paper presents JQueuer, a cloud-agnostic queuing system that supports the scheduling of a large number of jobs in containerised cloud environments. The paper also demonstrates how JQueuer, when integrated with a cloud application-level orchestrator and auto-scaling framework, called MiCADO, can be used to implement deadline-based execution policies. This novel technical solution provides an important step towards the cost-optimisation of batch processing and job submission applications. In order to test and prove the effectiveness of the solution, the paper presents experimental results when executing an agent-based simulation application using the open source REPAST simulation framework

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

ARCAFF: Active Region Classification and Flare Forecasting

The Sun is an enigmatic star that produces the most powerful explosive events in our solar system – solar flares and coronal mass ejections. Studying these phenomena can provide a unique opportunity to develop a deeper understanding of fundamental processes on the Sun, and critically, to better forecast space weather. The Active Region Classification and Flare Forecasting (ARCAFF) project will develop a beyond state-of-the-art flare forecasting system utilising end-to-end deep learning (DL) models to significantly improve upon traditional flare forecasting capabilities. The large amount of available space-based solar observations are an ideal candidate for this type of analysis, given DL effectiveness in modelling complex relationships. DL has already been successfully developed and deployed in weather forecasting, financial services, and health care domains but has not been fully exploited in the solar physics domain. ARCAFF will increase the accuracy and timeliness of current operational flare forecast products and create new time series flare forecasts with uncertainties. The forecasts will be benchmarked against current systems using international community standards. The datasets and codes developed for ARCAFF will be made openly available to support further research efforts and encourage their re-use. This presentation will provide a short overview of the project and present early results from the two ARCAFF topics, Active Region classifications using magnetogram cutouts Active Region detection and classification using full disk magnetograms

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population