Progress in the area of MHD stability and disruptions, since the publication of the 1999 ITER Physics Basis document Nucl. Fusion 39 2137-2664, is reviewed. Recent theoretical and experimental research has made important advances in both understanding and control of MHD stability in tokamak plasmas. Sawteeth are anticipated in the ITER baseline ELMy H-mode scenario, but the tools exist to avoid or control them through localized current drive or fast ion generation. Active control of other MHD instabilities will most likely be also required in ITER. Extrapolation from existing experiments indicates that stabilization of neoclassical tearing modes by highly localized feedback-controlled current drive should be possible in ITER. Resistive wall modes are a key issue for S128 Chapter 3: MHD stability, operational limits and disruptions advanced scenarios, but again, existing experiments indicate that these modes can be stabilized by a combination of plasma rotation and direct feedback control with non-axisymmetric coils. Reduction of error fields is a requirement for avoiding non-rotating magnetic island formation and for maintaining plasma rotation to help stabilize resistive wall modes. Recent experiments have shown the feasibility of reducing error fields to an acceptable level by means of non-axisymmetric coils, possibly controlled by feedback. The MHD stability limits associated with advanced scenarios are becoming well understood theoretically, and can be extended by tailoring of the pressure and current density profiles as well as by other techniques mentioned here. There have been significant advances also in the control of disruptions, most notably by injection of massive quantities of gas, leading to reduced halo current fractions and a larger fraction of the total thermal and magnetic energy dissipated by radiation. These advances in disruption control are supported by the development of means to predict impending disruption, most notably using neural networks. In addition to these advances in means to control or ameliorate the consequences of MHD instabilities, there has been significant progress in improving physics understanding and modelling. This progress has been in areas including the mechanisms governing NTM growth and seeding, in understanding the damping controlling RWM stability and in modelling RWM feedback schemes. For disruptions there has been continued progress on the instability mechanisms that underlie various classes of disruption, on the detailed modelling of halo currents and forces and in refining predictions of quench rates and disruption power loads. Overall the studies reviewed in this chapter demonstrate that MHD instabilities can be controlled, avoided or ameliorated to the extent that they should not compromise ITER operation, though they will necessarily impose a range of constraints.

The ‘Progress in the ITER Physics Basis’ (PIPB) document is an update of the ‘ITER Physics Basis’ (IPB), which was published in 1999 [1]. The IPB provided methodologies for projecting the performance of burning plasmas, developed largely through coordinated experimental, modelling and theoretical activities carried out on today's large tokamaks (ITER Physics R&D). In the IPB, projections for ITER (1998 Design) were also presented. The IPB also pointed out some outstanding issues. These issues have been addressed by the Participant Teams of ITER (the European Union, Japan, Russia and the USA), for which International Tokamak Physics Activities (ITPA) provided a forum of scientists, focusing on open issues pointed out in the IPB. The new methodologies of projection and control are applied to ITER, which was redesigned under revised technical objectives. These analyses suggest that the achievement of Q > 10 in the inductive operation is feasible. Further, improved confinement and beta observed with low shear (= high βp = ‘hybrid’) operation scenarios, if achieved in ITER, could provide attractive scenarios with high Q (> 10), long pulse (>1000 s) operation with beta

Analysis of Type I ELMs from ongoing experiments shows that ELM energy losses are correlated with the density and temperature of the pedestal plasma before the ELM crash. The Type I ELM plasma energy loss normalized to the pedestal energy is found to correlate across experiments with the collisionality of the pedestal plasma (ν * ped ), decreasing with increasing ν * ped . Other parameters affect the ELM size, such as the edge magnetic shear, etc, which influence the plasma volume affected by the ELMs. ELM particle losses are influenced by this ELM affected volume and are weakly dependent on other pedestal plasma parameters. In JET and DIII-D, under some conditions, ELMs can be observed ('minimum' Type I ELMs with energy losses acceptable for ITER), that do not affect the plasma temperature. The duration of the divertor ELM power pulse is correlated with the typical ion transport time from the pedestal to the divertor target (τ Front || = 2πRq 95 /c s,ped ) and not with the duration of the ELMassociated MHD activity. Similarly, the timescale of ELM particle fluxes is also determined by τ Front ||. The extrapolation of the present experimental results to ITER is summarized.

A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Because the signaling molecules RAS and ERK1/2 (extracellular signal-regulated kinases 1 and 2) are activated by an LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBPβ (CCAAT/Enhancerbinding protein-β) is a critical downstream mediator of ERK1/2 activation. Thus, ERK1/2 and C/ EBPβ constitute an in vivo LH-regulated signaling pathway that controls ovulation-and luteinization-related events.In the mammalian ovary, the female germ cells (oocytes) reside within the ovarian follicles and are surrounded by somatic cell-derived granulosa cells (GCs) and cumulus cells that have endocrine functions and control oocyte maturation. Female reproductive success depends on the growth of ovarian follicles and differentiation of GCs as well as oocyte maturation and ovulation (1,2). Although LH plays a critical role in the initiation of ovulation and in the terminal differentiation of GCs to luteal cells that compose the corpora lutea (CLs) and produce progesterone, the precise molecular targets in these processes remain ill-defined. Cyclic adenosine 3´,5´-monophosphate (cAMP) is a well-known mediator of LH action, but LH also induces expression of the epidermal growth factor

The molecular bridges that link the LH surge with functional changes in cumulus cells that possess few LH receptors are being unraveled. Herein we document that epidermal growth factor (EGF)-like factors amphiregulin (Areg), epiregulin (Ereg), and betacellulin (Btc) are induced in cumulus oocyte complexes (COCs) by autocrine and paracrine mechanisms that involve the actions of prostaglandins (PGs) and progesterone receptor (PGR). Areg and Ereg mRNA and protein levels were reduced significantly in COCs and ovaries collected from prostaglandin synthase 2 (Ptgs2) null mice and Pgr null (PRKO) mice at 4 h and 8 h after human chorionic gonadotropin, respectively. In cultured COCs, FSH/forskolin induced Areg mRNA within 0.5 h that peaked at 4 h, a process blocked by inhibitors of p38MAPK (SB203580), MAPK kinase (MEK) 1 (PD98059), and PTGS2 (NS398) but not protein kinase A (PKA) (KT5720). Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF receptor tyrosine kinase inhibitor AG1478 (AG), PD98059, and NS398. PGE2 reversed the inhibitory effects of AG on AREG-induced expression of Areg but not Ptgs2, placing Ptgs2 downstream of EGF-R signaling. Phorbol 12-myristate 13-acetate (PMA) and adenovirally expressed PGRA synergistically induced Areg mRNA in granulosa cells. In COCs, AREG not only induced genes that impact matrix formation but also genes involved in steroidogenesis (StAR, Cyp11a1) and immune cell-like functions (Pdcd1, Runx1, Cd52). Collectively, FSH-mediated induction of Areg mRNA via p38MAPK precedes AREG induction of Ptgs2 mRNA via ERK1/2. PGs acting via PTGER2 in cumulus cells provide a secondary, autocrine pathway to regulate expression of Areg in COCs showing critical functional links between G protein-coupled receptor and growth factor receptor pathways in ovulating follicles.