Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor ...implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing. GPR56 pursues this activity by associating with the tetraspanin CD81. We conclude that GPR56 inhibits natural cytotoxicity of human NK cells.
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•Hobit drives GPR56 expression in terminally differentiated NK cells•Upon cellular activation, NK cells downregulate GPR56 expression•GPR56 reduces NK-cell cytotoxicity and cytokine production•GPR56 represses effector functions by forming a complex with CD81
Activity of cytotoxic lymphocytes needs to be restricted at steady state. Chang et al. have established a role for an adhesion GPCR in the control of human NK cells. GPR56 is induced by Hobit, inhibits immediate effector functions by associating with the tetraspanin CD81, and declines upon cellular activation.
Gamma ray spectrometry measurements at high detector counting rates (on the order of 107 s−1 and higher) are relevant for high-temperature plasma diagnostics for existing tokamaks and during the ...development of gamma ray diagnostic systems for the ITER tokamak under construction. At high loads, to obtain spectra without distortion and with a small amount of dead time, it is necessary to use advanced scintillation detector signal processing methods, which can resolve superimposed pulses. Two algorithms that can be used for digital signal processing of scintillation gamma ray detectors with many piled-up pulses are considered in this article, the fitting and deconvolution methods. These algorithms are compared with both one another and two less sophisticated pulse-height analysis algorithms (maximum height and total sum under the peak) in applications that process model and measured signals. Baseline detection algorithms are also considered, which are necessary when processing signals from detectors. The algorithms are applied to LaBr3(Ce) detector signal processing. For the modeled signals, the best results in terms of the number of resolved events and energy resolution at counting rates up to 2 × 107 s−1 of the LaBr3(Ce) detector are demonstrated by the fitting method. In the real gamma ray measurements at a loading of 5.1 106 s−1, the deconvolution method demonstrated the best energy resolution.
Two neutron spectrometers based on a BC-501A liquid organic scintillator were calibrated. The calibration procedure included obtaining the spectrometers’ response functions to monoenergetic neutron ...emissions and estimating the detectors’ efficiency and is described in this paper. A 9Be(α, nγ)12C nuclear reaction was used as the neutron source. Simultaneous registration of neutrons and gamma quanta with 4.44 MeV energy enabled the extraction of monoenergetic neutrons corresponding to the first excited state of a 12C nucleus. This process is the basis of the neutron–gamma coincidence method, which was applied in the present experiments. The experiments were conducted using the cyclotron at Ioffe Institute, where α particles were accelerated to energies of 2.06, 5.35, 6.05, and 10.08 MeV. The angular dependence of the energy of produced neutrons provided a wide energy range of monoenergetic neutron emission at the same energy of the incident α particle. The response functions of the BC-501A spectrometers on the monoenergetic neutrons were obtained at energies of 1.9 to 10.4 MeV. The neutron registration efficiency of both detectors was estimated in the same energy range as the responses.
Neutron diagnostic system at the Globus-M2 tokamak Iliasova, M.V.; Shevelev, A.E.; Khilkevitch, E.M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2022, Volume:
1029
Journal Article
Peer reviewed
A neutron diagnostic system was developed at the Ioffe Institute as part of the Globus-M2 tokamak to optimize NBI heating conditions and evaluate heating efficiency. The system contains two compact ...neutron spectrometers based on the liquid organic scintillator BC-501A and two gas-discharge counters based on a 10B isotope. The BC-501A spectrometers were calibrated by measuring neutron emission produced in a 9Be(α,n)12C nuclear reaction on the cyclotron facility at the Ioffe Institute. In addition, in situ calibrations of the system, including the neutron spectrometers and the gas-discharge counters, was carried out using an Am–Be neutron source to provide accurate measurements of the total neutron yield from the plasma of the Globus-M2 tokamak. During the plasma experiments at the Globus-M2 tokamak, a deuterium beam was injected into the deuterium plasma that causes a yield of the DD-neutrons with ∼2.45 MeV energy. The neutron spectrometry diagnostic system was used to provide neutron measurements and detect the DD-neutrons in these experiments. The neutron yield and the DD-reaction rate during plasma discharges were evaluated. The energy distributions of neutrons emitted from plasma during discharges with neutron beam injection were reconstructed from the measured neutron spectra.
Studying the mechanism of Alfvén wave generation in plasma is important, since the interaction of these waves with energetic particles in tokamak-type reactors can increase the losses of energy and ...particles with the corresponding decrease in the efficiency of plasma heating and, under certain conditions, lead to the damage of structural elements of the system. Despite the previous detailed investigations of the excitation of Alfvén waves by superthermal particles in regimes with additional heating, the physics of Alfvén mode generation in discharges with ohmic heating of plasma is still not sufficiently studied. We have established that a significant factor inf luencing the development of Alfvén oscillations in ohmic discharge is the presence of runaway electrons. A physical mechanism explaining this relationship is proposed.
A gamma-ray spectrometer based on LaBr3(Ce) scintillator has been used for measurements of hard X-ray emission generated by runaway electrons in the FT-2 tokamak plasmas. Using of the fast LaBr3(Ce) ...has allowed extending count rate range of the spectrometer by a factor of 10. A developed digital processing algorithm of the detector signal recorded with a digitizer sampling rate of 250MHz has provided a pulse height analysis at count rates up to 107s−1. A spectrum deconvolution code DeGaSum has been applied for inferring the energy distribution of runaway electrons escaping from the plasma and interacting with materials of the FT-2 limiter in the vacuum chamber. The developed digital signal processing technique for LaBr3(Ce) spectrometer has allowed studying the evolution of runaways energy distribution in the FT-2 plasma discharges with time resolution of 1–5ms.
QS-21A is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy, given its exceedingly high level of potency and its favorable toxicity profile. ...Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing clinical trials involving QS-21A as a critical component for immune response augmentation in microgram doses. Herein is reported the first synthesis and structure verification of QS-21Aapi, applying novel glycosylation methodologies in the convergent modular construction of this rare and potent natural product immunostimulant.
A study of magnetically confined fast ions in tokamaks plays an important role in burning plasma research. To reach ignition and steady burning of a reactor plasma an adequate confinement of ...energetic ions produced by NBI heating, accelerated with ICRF and born in fusion reactions is essential to provide efficient heating of the bulk plasma. Thus, investigation of the fast ion behaviour is an immediate task for present-day large machines, such as JET, in order to understand the main mechanisms of slowing down, redistribution and losses, and to develop optimal plasma scenarios. Today's JET has an enhanced suite of fast ion diagnostics both of confined and lost ions that enable to significantly contribute to this important area of research. Fast ion populations of p, d, t, 3He and 4He, made with ICRF, NBI, and fusion reactions have been investigated in experiments on JET with sophisticated diagnostics in conventional and shear-reversed plasmas, exploring a wide range of effects. This paper will introduce to the JET fast-ion diagnostic techniques and will give an overview of recent observations. A synergy of the unique diagnostic set was utilised in JET, and studies of the response of fast ions to MHD modes (e.g. tornado modes, sawtooth crashes), fast 3He-ions behaviour in shear-reversed plasmas are impressive examples of that. Some results on fast ion losses in JET experiments with various levels of the toroidal field ripple will be demonstrated.
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