718 research outputs found

    Rotation and Neoclassical Ripple Transport in ITER

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    Neoclassical transport in the presence of non-axisymmetric magnetic fields causes a toroidal torque known as neoclassical toroidal viscosity (NTV). The toroidal symmetry of ITER will be broken by the finite number of toroidal field coils and by test blanket modules (TBMs). The addition of ferritic inserts (FIs) will decrease the magnitude of the toroidal field ripple. 3D magnetic equilibria with toroidal field ripple and ferromagnetic structures are calculated for an ITER steady-state scenario using the Variational Moments Equilibrium Code (VMEC). Neoclassical transport quantities in the presence of these error fields are calculated using the Stellarator Fokker-Planck Iterative Neoclassical Conservative Solver (SFINCS). These calculations fully account for ErE_r, flux surface shaping, multiple species, magnitude of ripple, and collisionality rather than applying approximate analytic NTV formulae. As NTV is a complicated nonlinear function of ErE_r, we study its behavior over a plausible range of ErE_r. We estimate the toroidal flow, and hence ErE_r, using a semi-analytic turbulent intrinsic rotation model and NUBEAM calculations of neutral beam torque. The NTV from the ∣n∣=18\rvert n \rvert = 18 ripple dominates that from lower nn perturbations of the TBMs. With the inclusion of FIs, the magnitude of NTV torque is reduced by about 75% near the edge. We present comparisons of several models of tangential magnetic drifts, finding appreciable differences only for superbanana-plateau transport at small ErE_r. We find the scaling of calculated NTV torque with ripple magnitude to indicate that ripple-trapping may be a significant mechanism for NTV in ITER. The computed NTV torque without ferritic components is comparable in magnitude to the NBI and intrinsic turbulent torques and will likely damp rotation, but the NTV torque is significantly reduced by the planned ferritic inserts

    Nonlinear dynamics and transport driven by energetic particle instabilities using a gyro-Landau closure model

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    Energetic particle (EP) destabilized Alfvén eigenmode (AE) instabilities are simulated for a DIII-D experimental case with a pulsed neutral beam using a gyro-Landau moments model which introduces EP phase-mixing effects through closure relations. This provides a computationally efficient reduced model which is applied here in the nonlinear regime over timescales that would be difficult to address with more complete models. The long timescale nonlinear evolution and related collective transport losses are examined including the effects of zonal flow/current generation, nonlinear energy cascades, and EP profile flattening. The model predicts frequencies and mode structures that are consistent with experimental observations. These calculations address issues that have not been considered in previous modelling: The EP critical gradient profile evolution in the presence of zonal flows/currents, and the dynamical nature of the saturated state. A strong level of intermittency is present in the predicted instability-driven transport; this is connected to the zonal flow growth and decay cycles and nonlinear energy transfers. Simulation of intermittent AE-enhanced EP transport will be an important issue for the protection of plasma facing components in the next generation of fusion devices.This material is based upon work supported by the US Department of Energy, Office of Science using the DIII-D National Fusion Facility, a DOE Office of Science user facility, under Awards DE-AC05-00OR22725, DE-FC02-04ER54698, and the US DOE SciDAC ISEP Center. Support is also acknowledged from project 2019-T1/AMB-13648 founded by the Comunidad de Madrid and Comunidad de Madrid (Spain)—multiannual agreement with UC3M Excelencia para el Profesorado Universitario EPUC3M14 Fifth regional research plan 2016-2020. This research used resources of the National Energy Research Scientific Computing Center (NERSC), a US Department of Energy Office of Science User Facility located at Lawrence Berkeley National Laboratory, operated under Contract No. DE-AC02- 05CH11231. We would like to thank Matt Beidler of Oak Ridge National Laboratory for helpful suggestions on this manuscript

    CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer

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    Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit the access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA tumor microenvironment promote concomitant chemotherapy delivery and increased antineoplastic response in murine models of PDA. Prior studies could not determine whether chemotherapy delivery or microenvironment modulation per se were the dominant features in treatment response, and such information could guide the optimal translation of these preclinical findings to patients. To distinguish between these possibilities, we used a chemical inhibitor of cytidine deaminase to stabilize and thereby artificially elevate gemcitabine levels in murine PDA tumors without disrupting the tumor microenvironment. Additionally, we used the FG-3019 monoclonal antibody (mAb) that is directed against the pleiotropic matricellular signaling protein connective tissue growth factor (CTGF/CCN2). Inhibition of cytidine deaminase raised the levels of activated gemcitabine within PDA tumors without stimulating neoplastic cell killing or decreasing the growth of tumors, whereas FG-3019 increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. The response to FG-3019 correlated with the decreased expression of a previously described promoter of PDA chemotherapy resistance, the X-linked inhibitor of apoptosis protein. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models, and by extension in PDA patients

    The monoenergetic approximation in stellarator neoclassical calculations

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    In the standard "monoenergetic" approach to numerical calculation of stellarator neoclassical transport, to expedite computation, ad-hoc changes are made to the kinetic equation so speed enters only as a parameter. Here we examine the validity of this approach by considering the effective particle trajectories in a model magnetic field. We find monoenergetic codes systematically under-predict the true trapped particle fraction, with the error in the trapped ion fraction being of order unity when the electric field is large, suggesting some results of these codes may be unreliable in this regime. This inaccuracy is independent of any errors introduced by approximation of the collision operator.Comment: 8 pages, 2 figures, submitted to Plasma Phys. Controlled Fusio

    Analysis of Alfven eigenmodes destabilization by energetic particles in TJ-II using a Landau-closure model

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    Alfven Eigenmodes (AE) can be destabilized by energetic particles in neutral beam injection (NBI) heated plasmas through inverse Landau damping and couplings with gap modes in the shear Alfven continua. We describe the linear evolution of the poloidal flux and the toroidal component of the vorticity in a full 3D system using the reduced MHD equations, density and parallel velocity moments for the energetic particles as well as the geodesic acoustic wave dynamics. A closure relation adds the Landau damping and resonant destabilization effects in the model. We apply the model to study the Alfven modes stability in TJ-II, performing a parametric analysis in a range of realistic values of energetic particle beta (beta(f)), ratios of thermal/Alfven velocities (V-th/V-A0), energetic particle density profiles and toroidal modes (n) including toroidal and helical couplings. The study predicts a large helical coupling between different toroidal modes and the destabilization of helical Alfven eigenmodes (HAE) with frequencies similar to the AE activity measured in TJ-II, between 50-400 kHz. The analysis has also revealed the destabilization of GAE (global Alfven eigenmodes), TAE (toroidal Alfven eigenmodes) and EPM (energetic particle modes). For the modes considered here, optimized TJ-II operations require a t profile in the range of [0.845, 0.979] to stabilize AEs in the inner and middle plasma. AEs in the plasma periphery cannot be fully stabilized, although for a configuration with t = [0.945, 1.079], only n = 7, 11, 15 AE are unstable with a growth rate 4 times smaller compared to the standard t = [1.54, 1.68] case and a frequency of 100 kHz. We reproduce the frequency sweeping evolution of the AE frequency observed in TJ-II as the t profile is varied. The AE frequency sweeping is caused by consecutive changes of the instability dominant modes between different helical families.This material based on work is supported both by the U.S. Department of Energy, Office of Science, under Contract DE-AC05-00OR22725 with UT-Battelle, LLC. This research was sponsored in part by the Ministerio of Economia y Competitividad of Spain under project no. ENE2015-68265-P. We also want to acknowledge Alexander Melnikov and the TJ-II group at CIEMAT for providing us the initial VMEC equilibria and useful discussions regarding the experimental phenomena

    Decision-to-incision times and maternal and infant outcomes.

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    Journal ArticleOBJECTIVE: To measure decision-to-incision intervals and related maternal and neonatal outcomes in a cohort of women undergoing emergency cesarean deliveries at multiple university-based hospitals comprising the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. METHODS: All women undergoing a primary cesarean delivery at a Network center during a 2-year time span were prospectively ascertained. Emergency procedures were defined as those performed for umbilical cord prolapse, placental abruption, placenta previa with hemorrhage, nonreassuring fetal heart rate pattern, or uterine rupture. Detailed information regarding maternal and neonatal outcomes, including the interval from the decision time to perform cesarean delivery to the actual skin incision, was collected. RESULTS: Of the 11,481 primary cesarean deliveries, 2,808 were performed for an emergency indication. Of these, 1,814 (65%) began within 30 minutes of the decision to operate. Maternal complication rates, including endometritis, wound infection, and operative injury, were not related to the decision-to-incision interval. Measures of newborn compromise including umbilical artery pH less than 7 and intubation in the delivery room were significantly greater when the cesarean delivery was commenced within 30 minutes, likely attesting to the need for expedited delivery. Of the infants with indications for an emergency cesarean delivery who were delivered more than 30 minutes after the decision to operate, 95% did not experience a measure of newborn compromise. CONCLUSION: Approximately one third of primary cesarean deliveries performed for emergency indications are commenced more than 30 minutes after the decision to operate, and the majority were for nonreassuring heart rate tracings. In these cases, adverse neonatal outcomes were not increased. LEVEL OF EVIDENCE: II-2

    Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

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    Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

    Alcohol exposure during late gestation: Multiple developmental outcomes in sheep

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    Alcohol consumption during pregnancy remains common in many countries. Exposure to even low amounts of alcohol (i.e. ethanol) in pregnancy can lead to the heterogeneous fetal alcohol spectrum disorders (FASD), while heavy alcohol consumption can result in the fetal alcohol syndrome (FAS). FAS is characterized by cerebral dysfunction, growth restriction and craniofacial malformations. However, the effects of lower doses of alcohol during pregnancy, such as those that lead to FASD, are less well understood. In this article, we discuss the findings of recent studies performed in our laboratories on the effects of fetal alcohol exposure using sheep, in which we investigated the effects of late gestational alcohol exposure on the developing brain, arteries, kidneys, heart and lungs. Our studies indicate that alcohol exposure in late gestation can (1) affect cerebral white matter development and increase the risk of hemorrhage in the fetal brain, (2) cause left ventricular hypertrophy with evidence of altered cardiomyocyte maturation, (3) lead to a decrease in nephron number in the kidney, (4) cause altered arterial wall stiffness and endothelial and smooth muscle function and (5) result in altered surfactant protein mRNA expression, surfactant phospholipid composition and pro-inflammatory cytokine mRNA expression in the lung. These findings suggest that fetal alcohol exposure in late gestation can affect multiple organs, potentially increasing the risk of disease and organ dysfunction in later life
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