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The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments. Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning. We established a methodology for the measurement of individual kinin peptides in order to study the function of the kallikrein-kinin system. The levels of kinin peptides in tissues were higher than in blood, confirming the primary tissue localization of the kallikrein-kinin system. Moreover, the separate measurement of bradykinin and kallidin peptides in man demonstrated the differential regulation of the plasma and tissue kallikrein-kinin systems, respectively. Kinin peptide levels were increased in the heart of rats with myocardial infarction, in tissues of diabetic and spontaneously hypertensive rats, and in urine of patients with interstitial cystitis, suggesting a role for kinin peptides in the pathogenesis of these conditions. By contrast, blood levels of kallidin, but not bradykinin, peptides were suppressed in patients with severe cardiac failure, suggesting that the activity of the tissue kallikrein-kinin system may be suppressed in this condition. Both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors increased bradykinin peptide levels. ACE and NEP inhibitors had different effects on kinin peptide levels in blood, urine, and tissues, which may be accounted for by the differential contributions of ACE and NEP to kinin peptide metabolism in the multiple compartments in which kinin peptide generation occurs. Measurement of the levels of individual kinin peptides has given important information about the operation of the kallikrein-kinin system and its role in physiology and disease states.

Developments presented at the 27th IAEA Fusion Energy Conference in several areas of experimental magnetic confinement fusion research relating to confinement physics, plasma stability, plasma performance and control are reviewed. First results were reported from significant new stellarator and tokamak facilities and wide-ranging studies of issues such as disruption mitigation, control of edge localized modes (ELMs), the influence of hydrogenic isotope on heat and particle transport, optimization of ELMy H-modes and advanced H-modes and the application of advanced control techniques have been performed in support of the preparations for ITER operation. [ABSTRACT FROM AUTHOR]

In the four-stage approach of the new ITER Research Plan, the first pre-fusion power operation (PFPO) phase will only have limited power available from external heating and current drive (H&CD) systems: 20–30 MW provided by the electron cyclotron resonance heating (ECRH) system. Accessing the H-mode confinement regime at such low auxiliary power requires operating at low magnetic field, plasma current and density, i.e. 1.8 T and 5 MA for a density between 40% and 50% of the Greenwald density. H-mode plasmas at 5 MA/1.8 T will also be investigated in the second PFPO phase when ITER will have its full complement of H&CD capabilities installed, i.e. 20–30 MW of ECRH, 20 MW of ion cyclotron resonance heating and 33 MW of neutral beam injection. This paper describes the operational constraints and the H&CD capabilities for such scenarios in hydrogen and helium plasmas, to assess their viability and the issues it will be possible to address with them. The modelling results show that 5 MA/1.8 T scenarios are viable and will allow the exploration of the H-mode physics and control issues foreseen in the ITER Research Programme in the PFPO phases. [ABSTRACT FROM AUTHOR]

The hybrid operating mode observed in several tokamaks is characterized by further enhancement over the high plasma confinement (H-mode) associated with reduced magneto-hydro-dynamic (MHD) instabilities linked to a stationary flat safety factor () profile in the core region. The proposed ITER hybrid operation is currently aiming at operating for a long burn duration (>1000 s) with a moderate fusion power multiplication factor, , of at least 5. This paper presents candidate ITER hybrid operation scenarios developed using a free-boundary transport modelling code, CORSICA, taking all relevant physics and engineering constraints into account. The ITER hybrid operation scenarios have been developed by tailoring the 15 MA baseline ITER inductive H-mode scenario. Accessible operation conditions for ITER hybrid operation and achievable range of plasma parameters have been investigated considering uncertainties on the plasma confinement and transport. ITER operation capability for avoiding the poloidal field coil current, field and force limits has been examined by applying different current ramp rates, flat-top plasma currents and densities, and pre-magnetization of the poloidal field coils. Various combinations of heating and current drive (H&CD) schemes have been applied to study several physics issues, such as the plasma current density profile tailoring, enhancement of the plasma energy confinement and fusion power generation. A parameterized edge pedestal model based on EPED1 added to the CORSICA code has been applied to hybrid operation scenarios. Finally, fully self-consistent free-boundary transport simulations have been performed to provide information on the poloidal field coil voltage demands and to study the controllability with the ITER controllers. [ABSTRACT FROM AUTHOR]