Visualization of Fast Ion Phase-Space Flow Driven by Alfvén Instabilities.

Fast ion phase-space flow, driven by Alfvén eigenmodes (AEs), is measured by an imaging neutral particle analyzer in the DIII-D tokamak. The flow firstly appears near the minimum safety factor at the injection energy of neutral beams, and then moves radially inward and outward by gaining and losing energy, respectively. The flow trajectories in phase space align well with the intersection lines of the constant magnetic moment surfaces and constant E-(ω/n)P_{ζ} surfaces, where E, P_{ζ} are the energy and canonical toroidal momentum of ions; ω and n are angular frequencies and toroidal mode numbers of AEs. It is found that the flow is so destructive that the thermalization of fast ions is no longer observed in regions of strong interaction. The measured phase-space flow is consistent with nonlinear hybrid kinetic-magnetohydrodynamics simulation. Calculations of the relatively narrow phase-space islands reveal that fast ions must transition between different flow trajectories to experience large-scale phase-space transport.

Observation of Critical-Gradient Behavior in Alfvén-Eigenmode-Induced Fast-Ion Transport.

Experiments in the DIII-D tokamak show that fast-ion transport suddenly becomes stiff above a critical threshold in the presence of many overlapping small-amplitude Alfvén eigenmodes (AEs). The threshold is phase-space dependent and occurs when particle orbits become stochastic due to resonances with AEs. Above threshold, equilibrium fast-ion density profiles are unchanged despite increased drive, and intermittent fast-ion losses are observed. Fast-ion Dα spectroscopy indicates radially localized transport of the copassing population at radii that correspond to the location of midcore AEs. The observation of stiff fast-ion transport suggests that reduced models can be used to effectively predict alpha profiles, beam ion profiles, and losses to aid in the design of optimized scenarios for future burning plasma devices.

Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.

The peroxisome biogenesis disorders (PBDs) are a group of lethal autosomal-recessive diseases caused by defects in peroxisomal matrix protein import, with the concomitant loss of multiple peroxisomal enzyme activities. Ten complementation groups (CGs) have been identified for the PBDs, with CG1 accounting for 51% of all PBD patients. We identified the human orthologue of yeast PEX1, a gene required for peroxisomal matrix protein import. Expression of human PEX1 restored peroxisomal protein import in fibroblasts from 30 CG1 patients, and PEX1 mutations were detected in multiple CG1 probands. A common PEX1 allele, G843D, is present in approximately half of CG1 patients and has a deleterious effect on PEX1 activity. Phenotypic analysis of PEX1-deficient cells revealed severe defects in peroxisomal matrix protein import and destabilization of PEX5, the receptor for the type-1 peroxisomal targetting signal, even though peroxisomes were present in these cells and capable of importing peroxisomal membrane proteins. These data demonstrate an important role for PEX1 in peroxisome biogenesis and suggest that mutations in this gene are the most common cause of the PBDs.

Charge exchange recombination spectroscopy measurements of DIII-D poloidal rotation with poloidal asymmetry in angular rotation.

Sixteen new tangential views for the charge exchange recombination (CER) spectroscopy diagnostic at DIII-D were installed in 2019 on the high-field side (HFS) of the tokamak with the main goal being the measurement of main-ion (deuterium) poloidal rotation. Eight of the new views are connected to spectrometers, which view the main-ion spectrum, adding main-ion measurements where there were previously none, and another eight new views increased the spatial resolution of existing impurity (carbon) measurements on the HFS. When combined with the existing low-field side measurements, measurements at two locations on flux surfaces out to a normalized minor radius of ≈0.6 are possible. The new tangential views have been used to measure the deuterium poloidal rotation directly for the first time using the Poloidal Asymmetry in Angular Rotation (PAAR) method. These new measurements enable further testing of the validity of neoclassical poloidal rotation predictions. Separate measurements of the radial electric field can be made for an impurity ion and the main-ion by combining the PAAR measurements with additional CER measurements of toroidal rotation, temperature, and density. These independent measurements of the radial electric field agree reasonably well.

The imaging fast ion D-alpha diagnostic (IFIDA) on DIII-D.

An Imaging Fast Ion D-alpha (IFIDA) diagnostic, characterized by a high optical spatial resolution of ≤2 mm for accurate validation of energetic particle (EP) transport models, has been developed on DIII-D. The diagnostic provides a 2D image in the radial-poloidal plane of the FIDA signal generated by EP emission after charge exchange with an injected neutral beam. A narrow passband filter integrates the FIDA signal in the spectral region of 650-652 nm (blue-shifted FIDA tail), which is mostly generated by co-passing EPs of energies E ≃ 40-80 keV. A beam modulation technique is employed to estimate the active component of the signal, which is then used to compute EP profiles and gradients with a higher accuracy than the standard spectroscopic FIDA diagnostic. The current diagnostic time resolution is ≃3 ms. In this work, the IFIDA diagnostic design is explained and data are compared with the spectroscopic FIDA diagnostic, which shares the same viewing geometry, to assess the improvements in EP profile reconstruction.

Diagnosis of fast ions produced by negative-ion neutral-beam injection with fast-ion deuterium-alpha spectroscopy.

Negative-ion neutral-beam injection (NNBI) is an important source of heating and current drive for next-step fusion devices where the injected energy can range from hundreds of keV to 1 MeV. Few diagnostics are suitable for phase-space resolved measurements of fast ions with energy in excess of 100 keV. A study to assess the feasibility of fast-ion deuterium-alpha (FIDA) spectroscopy to diagnose high-energy ions produced by NNBI is presented. Case studies with the Large Helical Device (LHD) and JT-60SA illustrate possible solutions for the measurement. The distribution function of fast ions produced by NNBI is calculated for both devices, and the FIDA spectrum is predicted by synthetic diagnostic simulation. Results with 180 keV NNBI in LHD show that, with a judicious choice of viewing geometry, the FIDA intensity is comparable to that obtained with the existing FIDA system. The measurement is more challenging with the 500 keV NNBI in JT-60SA. Simulations predict the FIDA intensity to be about 1% of the background bremsstrahlung, which is small compared to existing FIDA implementations with positive neutral-beam injection where signal levels are an order of magnitude larger. The sampling time required to extract the small FIDA signal is determined using a probabilistic approach. Results indicate that long averaging periods, from ones to tens of seconds, are needed to resolve the FIDA signal in JT-60SA. These long averaging times are suitable in long-pulse (∼100 s), steady-state devices like JT-60SA where an important measurement objective is the spatial profile of the slowing-down distribution of fast ions.

The peroxisome biogenesis factors pex4p, pex22p, pex1p, and pex6p act in the terminal steps of peroxisomal matrix protein import.

Peroxisomes are independent organelles found in virtually all eukaryotic cells. Genetic studies have identified more than 20 PEX genes that are required for peroxisome biogenesis. The role of most PEX gene products, peroxins, remains to be determined, but a variety of studies have established that Pex5p binds the type 1 peroxisomal targeting signal and is the import receptor for most newly synthesized peroxisomal matrix proteins. The steady-state abundance of Pex5p is unaffected in most pex mutants of the yeast Pichia pastoris but is severely reduced in pex4 and pex22 mutants and moderately reduced in pex1 and pex6 mutants. We used these subphenotypes to determine the epistatic relationships among several groups of pex mutants. Our results demonstrate that Pex4p acts after the peroxisome membrane synthesis factor Pex3p, the Pex5p docking factors Pex13p and Pex14p, the matrix protein import factors Pex8p, Pex10p, and Pex12p, and two other peroxins, Pex2p and Pex17p. Pex22p and the interacting AAA ATPases Pex1p and Pex6p were also found to act after Pex10p. Furthermore, Pex1p and Pex6p were found to act upstream of Pex4p and Pex22p. These results suggest that Pex1p, Pex4p, Pex6p, and Pex22p act late in peroxisomal matrix protein import, after matrix protein translocation. This hypothesis is supported by the phenotypes of the corresponding mutant strains. As has been shown previously for P. pastoris pex1, pex6, and pex22 mutant cells, we show here that pex4Delta mutant cells contain peroxisomal membrane protein-containing peroxisomes that import residual amounts of peroxisomal matrix proteins.

Red blood cell uptake of supplemental folate in patients on anticonvulsant drug therapy.

A group of epileptics (n = 18) and a control group (n = 10) of subjects aged 21-42 y were given 1-mg supplements of folate daily for 1 mo. Anticonvulsant therapy involved phenytoin alone or in combination with phenobarbital. Serum and red blood cell (RBC) folate levels were determined on days 1, 14, and 28. Mean serum and RBC folate levels were greater (p less than 0.05) for the control subjects compared with the epileptic subjects throughout the study. The percent increase in either serum or RBC folate was not different (p greater than 0.05) between the groups. The percent increase in serum folate when expressed as a percent of RBC folate was greater (p less than 0.05) for those epileptics who initially had deficient blood folate levels (serum folate less than 7 nmol/L; RBC folate less than 317 nmol/L) than those who did not. Deficient epileptics may have had an impaired RBC incorporation of circulating (serum) folate compared with nondeficient epileptics.

Gradient echo imaging of the lumbar spine.

Journal articles have presented pro and con views of gradient recalled echo (GRE) imaging of the lumbar spine, while it has been illustrated in textbooks that have advanced its diagnostic applicability. This paper reappraises GRE in light of evolving MRI technology. The conspicuity of anatomic structures on axial T1-weighted (T1W) spin-echo (SE) images were matched with T2 GRE images in 55 patients referred for evaluation of low back pain. Disc herniations were hyperintense on GRE images and readily separable from hypointense spondylophytes.

A community pediatric prevention partnership: linking schools, providers, and tertiary care services.

Integrated school health services traditionally have been provided through the local board of education or health department. However, increased competitiveness in the health care arena has challenged providers to find innovative models to deliver health services to school-aged children. This article describes a partnership among a hospital, a university, private providers, and a local school system and health department to provide school health services. Noteworthy aspects of the project include the organizational structure and funding of the program, implementation of a case management model, and a focus on documenting outcomes. This program has been successful in building local alliances to provide health care services to school children. Implications for other school systems struggling to fund health services for school-aged children are discussed.

Identification of a common PEX1 mutation in Zellweger syndrome.

The Zellweger spectrum of disease, encompassing Zellweger syndrome and the progressively milder phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease, is due to a failure to form functional peroxisomes. Cell fusion complementation studies demonstrated that these diseases are genetically heterogeneous, with two-thirds of all patients lying within a single complementation group, CG1. Molecular genetic and cell biology studies have shown that PEX1 is deficient in many CG1 patients. However, previous studies have focused on mildly affected patients and there is still no report of two mutant PEX1 alleles in any Zellweger syndrome patient. Furthermore, mutations in the PMP70 gene have also been identified in two Zellweger syndrome patients from CG1, raising the possibility that CG1 patients may represent a mixture of PEX1-deficient and PMP70-deficient individuals. To address the molecular basis of disease in Zellweger syndrome patients from CG1, we examined all 24 PEX1 exons in four patients, including both patients that have mutations in PMP70. PEX1 mutations were detected in all four patients, including a 1-bp insertion (c.2097insT) in exon 13 that was present in three of the four patients. Subsequent studies demonstrated that this mutation is present in one-half of all CG1 patients and correlates with the Zellweger syndrome phenotype. As this mutation leads to a loss of protein function its frequency makes it the most common cause of Zellweger syndrome, helping to explain the high percentage of patients that belong to CG1.

Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease.

Peroxisomal matrix protein import requires the action of two AAA ATPases, PEX1 and PEX6. Mutations in either the PEX1 or PEX6 gene are the most common cause of the lethal neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease and account for disease in 80% of all such patients. We report here that overexpression of PEX6 can suppress the phenotypes of certain PEX1-deficient cells, that overexpression of PEX1 can suppress the phenotypes of certain PEX6-deficient cells, and that these instances of suppression are allele-specific and require partial activity of the mutated gene. In addition to genetic evidence for interaction between PEX1 and PEX6, we find that the PEX1 and PEX6 proteins interact in the yeast two-hybrid assay and physically associate with one another in vitro. We previously identified a missense mutation in PEX1, G843D, which attenuates PEX1 function and is the most common cause of these diseases, present in one-third of all such patients. The G843D mutation attenuates the interaction between PEX1 and PEX6 in both the two-hybrid system and in vitro and appears to be suppressed by overexpression of PEX6. We conclude that PEX1 and PEX6 form a complex of central importance to peroxisome biogenesis and that mutations affecting this complex constitute the most common cause of the Zellweger syndrome spectrum of diseases.

Intrinsic cervical spinal cord deformation on MRI: "the distorted 'H' sign".

Extrinsic and intrinsic pathologic processes involving the spinal cord can affect its gross morphologic appearance. Contour-related abnormalities of the spinal cord can be determined by both noninvasive and invasive imaging techniques. Detailing internal dysmorphism of the spinal cord is more difficult to determine because the internal architecture of the cord is not usually visualized. Now magnetic resonance (MR) imaging can readily demonstrate the central "H" configuration of the normal spinal gray matter on axial T2* gradient-recall echo pulse sequences; thus, it should also be capable of demonstrating distortions of it. We initially reviewed 55 abnormal cervical spine 1.5-T MR imaging studies. Of 37 large lesions, 31 deformed the "H" whereas 18 small lesions did not. To compare potential differences in visualization of the "H" by MR scanners of different field strengths (1.5-0.5 T), a total of 125 additional patients were reviewed at different State University of New York (SUNY) sites. Visualization of the "H" varied from 51.4% at 1.5 T to 18.4% at 0.5 T. As resolution of the spinal cord increases on MR imaging, it becomes possible to more accurately map the altered cord "interior," which may have a detectable clinical (neurologic) counterpart.