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3D non-linear magnetohydrodynamics simulations of a double tearing mode with the JOREK code are presented in the context of trying to better understand the benign termination of runaway electron beams observed in some experiments. It is shown that the non-linear behaviour qualitatively depends on the resistivity η via its effect on how fast secondary, non-linearly destabilized, tearing modes grow relative to the primary mode. Within a certain range of η, a violent and global relaxation is observed, consistent with the 'Kadomtsev-predicted' reconnection region extending from almost the very centre up to the edge of the plasma.

We present two-dimensional global simulations of mitigated and vertically unstable disruptions in ITER in the presence of runaway electrons (REs). An elongated plasma in free-boundary equilibrium is subjected to an artificial thermal quench (TQ) and current profile flattening, followed by one or more massive material injections and a RE avalanche. Scenarios of major disruptions as well as upward and downward vertical displacement events are considered. Results provide important insights into the effects of RE formation, post TQ current profile, injection quantities and timings, and impurity flushout on the overall evolution of disruption and the plasma vertical motion thereof. Interplay between the various effects offers scope for potentially beneficial RE mitigation scenarios.

We review parametric decay instabilities (PDIs) expected in connection with electron cyclotron resonance heating (ECRH) of magnetically confined fusion plasmas, with a specific focus on conditions relevant for the ITER tokamak. PDIs involving upper hybrid (UH) waves are likely to occur in O-mode ECRH scenarios at ITER if electron density profiles allowing trapping of UH waves near the ECRH frequency are present. Such PDIs may occur near the plasma center in ITER full-field scenarios heated by 170 GHz O-mode ECRH and on the high-field side of half-field ITER plasmas heated by 110 GHz or 104 GHz O-mode ECRH. Additionally, 110 GHz O-mode ECRH of half-field ITER scenarios may have low ECRH absorption, due to the electron cyclotron resonance being located on the high-field side of the main plasma. This potentially allows PDIs driven by a significant amount of ECRH radiation reaching the UH resonance in X-mode to occur, as X-mode radiation can be generated by reflection of unabsorbed O-mode radiation from the high-field side wall. The occurrence of PDIs during ECRH may damage microwave diagnostics, such as the electron cyclotron emission and low-field side reflectometer systems at ITER, as well as complicate the calculation of heating and current drive characteristics. However, if PDIs are induced in a controlled manner, they may provide novel diagnostic tools and allow the generation of a moderate fast ion population in plasmas heated only by ECRH.

A promising method for the control of Edge Localized Modes (ELMs) in H-Mode tokamak plasmas is the application of Resonant Magnetic Perturbations (RMPs), where small helical field perturbations are introduced into the plasma via a set of external coils. While RMPs are used for suppression of ELMs in many present-day tokamaks, the mechanisms that lead to RMP-ELM control are still subject of debate. Here, we use the non-linear MHD code JOREK to investigate the penetration of the magnetic perturbation fields into ASDEX Upgrade (AUG) plasmas. We present an extension of the coupled JOREK-STARWALL code, that replaces the commonly used fixed boundary treatment with a free boundary treatment. Instead of prescribing the magnetic field at the boundary according to the vacuum field using Dirichlet boundary conditions, natural boundary conditions are applied, so that the magnetic field and plasma current density are evolving freely at the boundary. This allows a fully self-consistent development of the plasma response and the magnetic perturbation in the whole computational domain. The direct comparison of both approaches demonstrates that the artificial suppression of the plasma response with the fixed boundary treatment reduces the excitation of marginally stable modes. An overall larger perturbation is observed using the free boundary approach. The presented simulations are performed in realistic geometry with fully realistic plasma parameters and plasma flows based on reconstructions of experimental AUG equilibria. While the use of realistic plasma parameters makes the simulations particularly challenging, it also allows for quantitative comparisons to the experiment. When the RMP induced corrugation of the boundary is compared to electron density measurements from the lithium beam emission spectroscopy, only the free boundary approach shows excellent agreement with the experiment.

Background: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6–18 months on therapy. Objectives: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution. Methods: We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. Results: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these patients, 78.9% were BAb-positive after 3 months. BAb titers ≥ 1:2400 predicted NAb evolution with a sensitivity of 74.7% and a specificity of 98.5%. Cross-sectionally, MxA levels were significantly diminished in the BAb/NAb-positive samples; similarly, CXCL-10 and sTRAIL concentrations in BAb/NAb-positive and BAb-positive/NAb-negative samples, respectively, were also diminished compared to BAb/NAb-negative samples. Conclusions: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.

Background: The reasons for recurrent adenotonsillitis are poorly understood. Methods: The in situ composition of microbiota of nasal (5 children, 25 adults) and of hypertrophied adenoid and tonsillar tissue (50 children, 20 adults) was investigated using a broad range of fluorescent oligonucleotide probes targeted to bacterial rRNA. None of the patients had clinical signs of infection at the time of surgery. Results: Multiple foci of ongoing purulent infections were found within hypertrophied adenoid and tonsillar tissue in 83% of patients, including islands and lawns of bacteria adherent to the epithelium, with concomitant marked inflammatory response, fissures filled with bacteria and pus, and diffuse infiltration of the tonsils by bacteria, microabscesses, and macrophages containing phagocytosed microorganisms. Haemophilusinfluenzae mainly diffusely infiltrated the tissue, Streptococcus and Bacteroides were typically found in fissures, and Fusobacteria,Pseudomonas and Burkholderia were exclusively located within adherent bacterial layers and infiltrates. The microbiota were always polymicrobial. Conclusions: Purulent processes persist during asymptomatic periods of adenotonsillitis. Most bacteria involved in this process are covered by a thick inflammatory infiltrate, are deeply invading, or are located within macrophages. The distribution of the bacteria within tonsils may be responsible for the failure of antibiotic treatment.

The dynamics of large scale plasma instabilities can be strongly influenced by the mutual interaction with currents flowing in conducting vessel structures. Especially eddy currents caused by time-varying magnetic perturbations and halo currents flowing directly from the plasma into the walls are important. The relevance of a resistive wall model is directly evident for Resistive Wall Modes (RWMs) or Vertical Displacement Events (VDEs). However, also the linear and non-linear properties of most other large-scale instabilities may be influenced significantly by the interaction with currents in conducting structures near the plasma. The understanding of halo currents arising during disruptions and VDEs, which are a serious concern for ITER as they may lead to strong asymmetric forces on vessel structures, could also benefit strongly from these non-linear modeling capabilities. Modeling the plasma dynamics and its interaction with wall currents requires solving the magneto-hydrodynamic (MHD) equations in realistic toroidal X-point geometry consistently coupled with a model for the vacuum region and the resistive conducting structures. With this in mind, the non-linear finite element MHD code JOREK [1, 2] has been coupled [3] with the resistive wall code STARWALL [4], which allows us to include the effects of eddy currents in 3D conducting structures in non-linear MHD simulations. This article summarizes the capabilities of the coupled JOREK-STARWALL system and presents benchmark results as well as first applications to non-linear simulations of RWMs, VDEs, disruptions triggered by massive gas injection, and Quiescent H-Mode. As an outlook, the perspectives for extending the model to halo currents are described.

Background Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioactivity in NAB-positive patients with MS. Methods NAB-positive patients with MS were treated with 8 MIU IFNβ-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee. Results Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12–3234) and RNA (2186, range 114–7525) area under the curve levels for the four measurements at each IFNβ injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0–2709) for MxA protein after 8 MIU i.v. and 254 (0–1200) after s.c., and 1763 (25–7188) for MxA RNA after 8 MIU i.v., and 557 (5–2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNβ-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed. Discussion The results indicate that i.v. administration of IFNβ can restore bioavailability of IFNβ in patients with NABs.

In tokamaks, a leading platform for fusion energy, periodic filamentary plasma eruptions known as edge-localized modes occur in plasmas with high-energy confinement and steep pressure profiles at the plasma edge. These edge-localized modes could damage the tokamak wall but can be suppressed using small three-dimensional magnetic perturbations. Here we demonstrate that these magnetic perturbations can change the magnetic topology just inside the steep gradient region of the plasma edge. We identify signatures of a magnetic island, and their observation is linked to the suppression of edge-localized modes. We compare high-resolution measurements of perturbed magnetic surfaces with predictions from ideal magnetohydrodynamic theory where the magnetic topology is preserved. Although ideal magnetohydrodynamics adequately describes the measurements in plasmas exhibiting edge-localized modes, it proves insufficient for plasmas where these modes are suppressed. Nonlinear resistive magnetohydrodynamic modelling supports this observation. Our study experimentally confirms the predicted role of magnetic islands in inhibiting the occurrence of edge-localized modes. This will be beneficial for physics-based predictions in future fusion devices to control these modes. The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.

Tumourigenesis caused by the Bcr/Abl oncoprotein is a multi‐step process proceeding from initial to tumour‐maintaining events and finally results in a complex tumour‐supporting network. A key to successful cancer therapy is the identification of critical functional nodes in an oncogenic network required for disease maintenance. So far, the transcription factors Stat3 and Stat5a/b have been implicated in bcr/abl ‐induced initial transformation. However, to qualify as a potential drug target, a signalling pathway must be required for the maintenance of the leukaemic state. Data on the roles of Stat3 or Stat5a/b in leukaemia maintenance are elusive. Here, we show that both, Stat3 and Stat5 are necessary for initial transformation. However, Stat5‐ but not Stat3‐deletion induces G 0 /G 1 cell cycle arrest and apoptosis of imatinib‐sensitive and imatinib‐resistant stable leukaemic cells in vitro . Accordingly, Stat5‐abrogation led to effective elimination of myeloid and lymphoid leukaemia maintenance in vivo . Hence, we identified Stat5 as a vulnerable point in the oncogenic network downstream of Bcr/Abl representing a case of non‐oncogene addiction (NOA).