The Fusion Nuclear Science Facility (FNSF) is examined here as part of a two step program from ITER to commercial power plants. This first step is considered mandatory to establish the materials and ...component database in the real fusion in-service environment before proceeding to larger electricity producing facilities. The FNSF can be shown to make tremendous advances beyond ITER, toward a power plant, particularly in plasma duration and fusion nuclear environment. A moderate FNSF is studied in detail, which does not generate net electricity, but does reach the power plant blanket operating temperatures. The full poloidal Dual Coolant Lead Lithium (DCLL) blanket is chosen, with alternates being the Helium Cooled Lead Lithium (HCLL) and Helium Cooled Ceramic Breeder/Pebble Bed (HCCB/PB). Several power plant relevant choices are made in order to follow the philosophy of targeted technologies. Any fusion core component must be qualified by fusion relevant neutron testing and highly integrated non-nuclear testing before it can be installed on the FNSF in order to avoid the high probability of constant failures in a plasma-vacuum system. A range of missions for the FNSF, or any fusion nuclear facility on the path toward fusion power plants, are established and characterized by several metrics. A conservative physics strategy is pursued to accommodate the transition to ultra-long plasma pulses, and parameters are chosen to represent the power plant regime to the extent possible. An operating space is identified, and from this, one point is chosen for further detailed analysis, with R=4.8m, a=1.2m, IP=7.9 MA, BT=7.5T, βN<2.7, n/nGr=0.9, fBS=0.52, q95=6.0, H98 ∼1.0, and Q=4.0. The operating space is shown to be robust to parameter variations. A program is established for the FNSF to show how the missions for the facility are met, with a He/H, a DD and 5 DT phases. The facility requires ∼25years to complete its DT operation, including 7.8 years of neutron production, and the remaining spent on inspections and maintenance. The DD phase is critical to establish the ultra-long plasma pulse lengths. The blanket testing strategy is examined, and shows that many sectors have penetrations for heating and current drive (H/CD), diagnostics, or Test Blanket Modules (TBMs). The hot cell is a critical facility element in order for the FNSF to perform its function of developing the in-service material and component database. The pre-FNSF R&D is laid out in terms of priority topics, with the FNSF phases driving the time-lines for R&D completion. A series of detailed technical assessments of the FNSF operating point are reported in this issue, showing the credibility of such a step, and more detailed emphasis on R&D items to pursue. These include nuclear analysis, thermo-mechanics and thermal-hydraulics, liquid metal thermal hydraulics, transient thermo-mechanics, tritium analysis, maintenance assessment, magnet specification and analysis, materials assessments, core and scrape-off layer (SOL)/divertor plasma examinations.
Surface wave dynamics of vertical falling films under monochromatic-frequency flowrate-forcing perturbations is computed by the direct simulation of Navier–Stokes equations using the Volume of Fluid ...(VOF) method to track free surfaces and the Continuum Surface Force (CSF) model to account for dynamic boundary conditions at free surfaces. The numerical VOF–CSF model is completely formulated, and more attention is given to understanding instabilities of thin films. At low frequency and high flowrate, the small inlet disturbance develops into large solitary waves preceded by small capillary bow waves. The circulation flow compatible with the solitary wave size is observed in the solitary peak. On the other hand, at high frequency and low
Re, small-amplitude waves in nearly sinusoidal shape without fore-running capillary waves are formed on the surface. The quasi-periodic waveforms are found to occur at the nearly sinusoidal wave regime. The slight increase in wave-amplitude and wavelength, and decrease in residual thickness as waves evolves downstream are observed for both solitary waves and sinusoidal types. The variation of velocity and pressure along a wave are strong at the wave trough and capillary wave region, due to the large surface curvature there. The pressure variation perpendicular to the wall is negligible and only a small variation is observed at the solitary wave trough and capillary region.
Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the ...study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy.
To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo.
The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS.
Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303).
Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment.
The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval CI, 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P =.72).
Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits.
The pathway to the successful development of an attractive power plant implies a successful strategy in developing a number of key fusion systems forming part of the power plant. Here, an example ...strategy and pathway in developing a blanket system based on the lead–lithium alloy breeder is described as an illustration. A historical perspective of the development of the various lead–lithium based blankets is summarized and a thorough description of the key issues driving the blanket concept assessment is provided. A comprehensive assessment of the helium-cooled lead–lithium (HCLL) and dual-coolant lead–lithium (DCLL) blanket concepts is presented in the context of this development pathway and in helping guide the choice of the initial concept to be tested in ITER as part of an overall progressive development strategy.
Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 ...controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10
) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders
, epilepsy and severe neurodevelopmental disorders
, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk
, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.
The mechanical force of blood flow is a fundamental determinant of vascular homeostasis. This frictional stimulation of cells, fluid shear stress (FSS), is increasingly recognised as being essential ...to placental development and function. Here, we focus on the role of FSS in regulating fetoplacental circulatory flow, both in normal pregnancy and that affected by fetal growth restriction (FGR).
The fetus is reliant on placental perfusion to meet its circulatory and metabolic demands. Failure of normal vascular adaptation and the mechanisms enabling responsive interaction between fetoplacental and maternal circulations can result in FGR. FSS generates vasodilatation at least partly through the release of endothelial nitric oxide, a process thought to be vital for adequate blood flow. Where FGR is caused by placental dysfunction, placental vascular anatomy is altered, alongside endothelial dysfunction and hypoxia, each impacting upon the complex balance of FSS forces.
Identifying specific mechanical sensors and the mechanisms governing how FSS force is converted into biochemical signals is a fast-paced area of research. Here, we raise awareness of Piezo1 proteins, recently discovered to be FSS-sensitive in fetoplacental endothelium, and with emerging roles in NO generation, vascular tone and angiogenesis. We discuss the emerging concept that activating mechanosensors such as Piezo1 ultimately results in the orchestrated processes of placental vascular adaptation. Piecing together the mechanisms governing endothelial responses to FSS in placental insufficiency is an important step towards developing new treatments for FGR.
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The dual-coolant lead-lithium, or DCLL, blanket concept is of strong interest in the US fusion technology program. In the DCLL blanket, the flow channel insert (FCI) is a critical component. FCIs ...must have low electrical and thermal conductivity and be compatible with lead–lithium eutectic alloy (Pb–17Li) at elevated temperatures. FCIs must retain structural integrity and desirable properties even under irradiation and large temperature gradients during operation. FCIs must not fail in such a way that Pb–17Li enters the FCI and changes its electrical or thermal conductivity significantly. Another important issue for the DCLL is the development of a suitable tritium extraction from the Pb–17Li to achieve low tritium partial pressure, thus facilitating decisive tritium control. In this paper, the state of DCLL development in the US is presented including recent design modifications and results from recent R&D efforts. Such R&D includes the progress on development and property quantification of SiC/SiC composites and SiC foams as candidate FCI materials; Pb–17Li material capability and infiltration studies; simulations of MHD Pb–17Li flow characteristics and of resultant temperature distributions; and the analysis of FCI stress states based on these thermal loads. In addition, tritium extraction from Pb–17Li based on a vacuum permeator concept is shown to have the potential to achieve the desired tritium control. A discussion of DCLL optimization and unresolved DCLL issues and future R&D needs is also presented.
Liquid metal plasma facing components (PFCs) have been identified as an alternative material for fusion plasma experiments. The use of a liquid conductor where significant magnetic fields are present ...is considered risky, with the possibility of macroscopic fluid motion and possible ejection into the plasma core. Analysis is carried out on thermoelectric magnetohydrodynamic (TEMHD) forces caused by temperature-gradients in the liquid-container system itself in addition to scrape-off-layer currents interacting with the PFC from a diverted plasma. Capillary effects at the liquid-container interface will be examined which govern droplet ejection criteria. Stability of the interface is determined using linear stability methods.
In addition to application to liquid metal PFCs, thin film liquid metal effects have application to current and future devices where off-normal events may liquefy portions of the first wall and other plasma facing components.
In this paper, an approach to simulating magnetohydrodynamic (MHD) flows based on the lattice Boltzmann method (LBM) is presented. The dynamics of the flow are simulated using a so-called multiple ...relaxation time (MRT) lattice Boltzmann equation (LBE), in which a source term is included for the Lorentz force. The evolution of the magnetic induction is represented by introducing a vector distribution function and then solving an appropriate lattice kinetic equation for this function. The solution of both distribution functions are obtained through a simple, explicit, and computationally efficient stream-and-collide procedure. The use of the MRT collision term enhances the numerical stability over that of a single relaxation time approach. To apply the methodology to solving practical problems, a new extrapolation-based method for imposing magnetic boundary conditions is introduced and a technique for simulating steady-state flows with low magnetic Prandtl number is developed. In order to resolve thin layers near the walls arising in the presence of high magnetic fields, a non-uniform gridding strategy is introduced through an interpolated-streaming step applied to both distribution functions. These advances are particularly important for applications in fusion engineering where liquid metal flows with low magnetic Prandtl numbers and high Hartmann numbers are introduced. A number of MHD benchmark problems, under various physical and geometrical conditions are presented, including 3-D MHD lid driven cavity flow, high Hartmann number flows and turbulent MHD flows, with good agreement with prior data. Due to the local nature of the method, the LBM also demonstrated excellent performance on parallel machines, with almost linear scaling up to 128 processors for a MHD flow problem.
Several high-priority near-term potential research activities to address fusion nuclear science challenges are summarized. General recommendations include: (1) Research should be preferentially ...focused on the most technologically advanced options (i.e., options that have been developed at least through the single-effects concept exploration stage, technology readiness levels >3), (2) Significant near-term progress can be achieved by modifying existing facilities and/or moderate investment in new medium-scale facilities, and (3) Computational modeling for fusion nuclear sciences is generally not yet sufficiently robust to enable truly predictive results to be obtained, but large reductions in risk, cost and schedule can be achieved by careful integration of experiment and modeling.
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