ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions.However, mutations in ERCC1 or XPF in humans or mice cause a more severe phenotype than absence of NER, prompting a search for novel repair activities of the nuclease. In Saccharomyces cerevisiae, orthologs of ERCC1-XPF (Rad10-Rad1) participate in the repair of double-strand breaks (DSBs). Rad10-Rad1 contributes to two error-prone DSB repair pathways: microhomology-mediated end joining (a Ku86-independent mechanism) and single-strand annealing. To determine if ERCC1-XPF participates in DSB repair in mammals, mutant cells and mice were screened for sensitivity to gamma irradiation. ERCC1-XPF-deficient fibroblasts were hypersensitive to gamma irradiation, and ␥H2AX foci, a marker of DSBs, persisted in irradiated mutant cells, consistent with a defect in DSB repair. Mutant mice were also hypersensitive to irradiation, establishing an essential role for ERCC1-XPF in protecting against DSBs in vivo. Mice defective in both ERCC1-XPF and Ku86 were not viable. However, Ercc1 ؊/؊ Ku86 ؊/؊ fibroblasts were hypersensitive to gamma irradiation compared to single mutants and accumulated significantly greater chromosomal aberrations. Finally, in vitro repair of DSBs with 3 overhangs led to large deletions in the absence of ERCC1-XPF. These data support the conclusion that, as in yeast, ERCC1-XPF facilitates DSB repair via an end-joining mechanism that is Ku86 independent.ERCC1-XPF is a highly conserved endonuclease identified for its essential role in nucleotide excision repair (NER) of helix-distorting DNA lesions, in particular, UV-induced damage (4, 74). Defects in NER cause xeroderma pigmentosum (XP), a rare disorder characterized by photosensitivity, a dramatically increased risk of skin cancer, and neurodegeneration in severe cases. In contrast, the only reported patient with a mutation in ERCC1 had severe congenital anomalies (cerebrooculo-facial-skeletal syndrome) (33). Patients with subtle mutations in XPF have a mild form of XP (46), consistent with only a partial defect in NER. However, a mutation in XPF that severely compromises protein levels causes dramatically accelerated aging (53). This observation implies additional functions for mammalian ERCC1-XPF distinct from NER. Consistent with that, ERCC1-and XPF-deficient mice have a much more severe phenotype than mice defective in NER. Xpa Ϫ/Ϫ mice with undetectable NER are indistinguishable from wildtype (WT) mice until challenged with carcinogens (12). In contrast, Ercc1Ϫ/Ϫ and Xpf Ϫ/Ϫ mice have a constellation of progeroid symptoms affecting the musculoskeletal, dermatologic, hepatobiliary, renal, and hematopoietic systems (48,53,79,84) and die of liver failure before sexual maturation (72).XPF contains the catalytic domain of the nuclease (18), whereas ERCC1 is required for DNA binding and stabilization of XPF (51, 80). The endonuclease is structure specific, incising double-stranded DNA 5Ј to a junction with single-stranded DNA. Thus, ERCC1-XPF can remove 3Ј...

Varying the neutral beam injection (NBI) mix reveals a clear pedestal-top rotation threshold for edge localized mode (ELM) suppression by resonant magnetic perturbations. Guided by expectations for the RMP penetration mechanism, the rotation threshold is found to correspond to a critical radius for the ExB rotation zero-crossing. No such critical radius is observed for the electron perpendicular rotation zero-crossing. Varying the amount and ratio of power in different NBI source geometries (termed the NBI mix) also reveals that the rotation threshold can be crossed at widely varying total injected NBI torques. Computing the local torque density at the edge, the rotation threshold is found to be crossed when the local edge NBI torque is negative in nearly all discharges. Reducing the upper triangularity from the ITERsimilar value of 0.3 to 0.1 significantly reduces the pedestal height and width. This in turn: 1) Increases the rotation threshold and yields a more outward critical ExB rotation zero-crossing location. 2) Decreases the density threshold, consistent with a comparable collisionality range at lower pedestal temperatures. 3) Increases the input torque requirement, due to observed lower confinement and smaller intrinsic torque. These findings represent an important step along the road to predicting ELM suppression access conditions in future tokamaks such as ITER, where the toroidal rotation is expected to be low and consequently the rotation zero-crossing far from the pedestal-top.

Divertor detachment offers a promising solution to the challenge of plasma-wall interactions for steady-state operation of fusion reactors. Here, we demonstrate the excellent compatibility of actively controlled full divertor detachment with a high-performance (βN ~ 3, H98 ~ 1.5) core plasma, using high-βp (poloidal beta, βp > 2) scenario characterized by a sustained core internal transport barrier (ITB) and a modest edge transport barrier (ETB) in DIII-D tokamak. The high-βp high-confinement scenario facilitates divertor detachment which, in turn, promotes the development of an even stronger ITB at large radius with a weaker ETB. This self-organized synergy between ITB and ETB, leads to a net gain in energy confinement, in contrast to the net confinement loss caused by divertor detachment in standard H-modes. These results show the potential of integrating excellent core plasma performance with an efficient divertor solution, an essential step towards steady-state operation of reactor-grade plasmas.

The Madison plasma dynamo experiment (MPDX) is a novel, versatile, basic plasma research device designed to investigate flow driven magnetohydrodynamic instabilities and other high-b phenomena with astrophysically relevant parameters. A 3 m diameter vacuum vessel is lined with 36 rings of alternately oriented 4000 G samarium cobalt magnets, which create an axisymmetric multicusp that contains $14 m 3 of nearly magnetic field free plasma that is well confined and highly ionized (>50%). At present, 8 lanthanum hexaboride (LaB 6 ) cathodes and 10 molybdenum anodes are inserted into the vessel and biased up to 500 V, drawing 40 A each cathode, ionizing a low pressure Ar or He fill gas and heating it. Up to 100 kW of electron cyclotron heating power is planned for additional electron heating. The LaB 6 cathodes are positioned in the magnetized edge to drive toroidal rotation through J Â B torques that propagate into the unmagnetized core plasma. Dynamo studies on MPDX require a high magnetic Reynolds number Rm > 1000, and an adjustable fluid Reynolds number 10 < Re < 1000, in the regime where the kinetic energy of the flow exceeds the magnetic energy (M 2 A ¼ ðv=v A Þ 2 > 1). Initial results from MPDX are presented along with a 0-dimensional power and particle balance model to predict the viscosity and resistivity to achieve dynamo action. V C 2014 AIP Publishing LLC.

Resonant magnetic perturbations (n  =  3 RMPs) are used to suppress large amplitude ELMs and mitigate naturally occurring ‘grassy’-ELMs in DIII-D plasmas relevant to the ITER steady-state mission. Fully non-inductive discharges in the ITER shape and pedestal collisionality (  ≈  0.05–0.15) are routinely achieved in DIII-D with RMP suppression of the Type-I ELMs. The residual grassy-ELMs deliver a low peak heat flux to the divertor as low as 1.2×  the inter-ELM heat flux in plasmas with sustained high H-factor (H98y2  ≈  1.2). The operating window for the RMP grassy-ELM regime is q95  =  5.3–7.1 and external torque in the range 9–0.7 Nm in the co-Ip direction, which is in the range required for a steady-state tokamak reactor. The RMP grassy-ELM regime is associated with a two-step pedestal, with strong flattening of the density around the zero crossing in the E  ×  B shear. The edge magnetic response of the plasma to the n  =  3 RMP is found to be  ≈2–3×  larger than for comparable ITER baseline plasmas (βN  ≈  1.8, q95  ≈  3.1). The amplification of the RMP is consistent with the weak magnetic perturbation level (δB/B  ≈  1  ×  10−4) required for effective Type-I ELM suppression. Cyclic variations in the pedestal pressure, width, and toroidal rotation are observed in these plasmas, correlated with cyclic variations in the strength and frequency of the grassy-ELMs. Extended MHD analysis and magnetic measurements indicate that these pedestal pulsations are driven by cyclic variations in the resonant field strength at the top of the pedestal. These pedestal pulsations reveal that the grassy-ELMs is correlated with the proximity of the pedestal to the low-n peeling-ballooning mode stability boundary. The use of low amplitude magnetic fields to access grassy-ELM conditions free of Type-I ELMs in high beta poloidal plasmas (βP  ≈  1.5–2.0) opens the possibility for the further optimization of the steady-state tokamak by use of edge resonant magnetic perturbations.