First application of data assimilation-based control to fusion plasma.

Magnetic fusion plasmas, which are complex systems comprising numerous interacting elements, have large uncertainties. Therefore, future fusion reactors require prediction-based advanced control systems with an adaptive system model and control estimation robust to uncertainties in the model and observations. To address this challenge, we introduced a control approach based on data assimilation (DA), which describes the system model adaptation and control estimation based on the state probability distribution. The first implementation of a DA-based control system was achieved at the Large Helical Device to control the high temperature plasma. The experimental results indicate that the control system enhanced the predictive capability using real-time observations and adjusted the electron cyclotron heating power for a target temperature. The DA-based control system provides a flexible platform for advanced control in future fusion reactors.

Collective Thomson scattering diagnostic with in situ calibration system for velocity space analysis in large helical device.

A collective Thomson scattering (CTS) diagnostic with a ±3 GHz band around a 77 GHz gyrotron probe beam was developed to measure the velocity distribution of bulk and fast ions in high-temperature plasmas. We propose a new in situ calibration method for a CTS diagnostic system combined with a raytracing code. The method is applied in two situations for electron cyclotron emission in plasmas and in a CTS diagnostic with a modulated probe beam. Experimental results highlight the importance of refraction correction in probe and receive beams. The CTS spectrum is measured with the in situ calibrated CTS receiver and responds to fast ions originating from a tangential neutral beam with an energy of 170 keV and from a perpendicular beam with an energy of 60 keV, both in the large helical device. From a velocity space analysis model, the results elucidate the measured anisotropic CTS spectrum caused by fast ions. The calibration methods and analyses demonstrated here are essential for CTS, millimeter-wave diagnostics, and electron cyclotron heating required under fusion reactor conditions.

Correction: Induced pluripotent stem cell-derived monocytic cell lines from a NOMID patient serve as a screening platform for modulating NLRP3 inflammasome activity.

[This corrects the article DOI: 10.1371/journal.pone.0237030.].

Induced pluripotent stem cell-derived monocytic cell lines from a NOMID patient serve as a screening platform for modulating NLRP3 inflammasome activity.

Curative therapeutic options for a number of immunological disorders remain to be established, and approaches for identifying drug candidates are relatively limited. Furthermore, phenotypic screening methods using induced pluripotent stem cell (iPSC)-derived immune cells or hematopoietic cells need improvement. In the present study, using immortalized monocytic cell lines derived from iPSCs, we developed a high-throughput screening (HTS) system to detect compounds that inhibit IL-1ß secretion and NLRP3 inflammasome activation from activated macrophages. The iPSCs were generated from a patient with neonatal onset multisystem inflammatory disease (NOMID) as a model of a constitutively activated NLRP3 inflammasome. HTS of 4,825 compounds including FDA-approved drugs and compounds with known bioactivity identified 7 compounds as predominantly IL-1ß inhibitors. Since these compounds are known inflammasome inhibitors or derivatives of, these results prove the validity of our HTS system, which can be a versatile platform for identifying drug candidates for immunological disorders associated with monocytic lineage cells.

Identification of a High-Frequency Somatic NLRC4 Mutation as a Cause of Autoinflammation by Pluripotent Cell-Based Phenotype Dissection.

OBJECTIVE: To elucidate the genetic background of a patient with neonatal-onset multisystem inflammatory disease (NOMID) with no NLRP3 mutation. METHODS: A Japanese male child diagnosed as having NOMID was studied. The patient did not have any NLRP3 mutation, even as low-frequency mosaicism. We performed whole-exome sequencing on the patient and his parents. Induced pluripotent stem cells (iPSCs) were established from the patient's fibroblasts. The iPSCs were then differentiated into monocyte lineage to evaluate the cytokine profile. RESULTS: We established multiple iPSC clones from a patient with NOMID and incidentally found that the phenotypes of monocytes from iPSC clones were heterogeneous and could be grouped into disease and normal phenotypes. Because each iPSC clone was derived from a single somatic cell, we hypothesized that the patient had somatic mosaicism of an interleukin-1ß-related gene. Whole-exome sequencing of both representative iPSC clones and the patient's blood revealed a novel heterozygous NLRC4 mutation, p.T177A (c.529A>G), as a specific mutation in diseased iPSC clones. Knockout of the NLRC4 gene using the clustered regularly interspaced short palindromic repeat/Cas9 system in a mutant iPSC clone abrogated the pathogenic phenotype. CONCLUSION: Our findings indicate that the patient has somatic mosaicism of a novel NLRC4 mutation. To our knowledge, this is the first case showing that somatic mutation of NLRC4 causes autoinflammatory symptoms compatible with NOMID. The present study demonstrates the significance of prospective genetic screening combined with iPSC-based phenotype dissection for individualized diagnoses.