Spatial and spectral resolution of the plasma Doppler reflectometry

An approach to numerical simulations of microwave scattering in Doppler reflectometry is developed that is based on calculations of the two-dimensional spatial weighting function in the Born approximation. The knowledge of the spatial weighting (or instrumental) function, which contains complete information on both forward and backward scattering processes, allows one to calculate the output signal of a quadrature diagnostic detector for any given distribution of the electron plasma density fluctuations. The weighting functions were computed for axisymmetric distributions of the background plasma density and for arbitrarily specified fields in the mouths of the emitting and receiving antennas. Simulations carried out for different model representations of the scattering fluctuations yielded quantitative estimates of both the spatial and wavenumber resolutions of Doppler reflectometry. The simulations showed that the resolution of the method proposed worsens with increasing curvature of the cut-off surface. Conditions are determined under which the resolution of the diagnostics in small-and medium-size tokamaks can be substantially improved by using converging microwave beams. The possibility of utilizing focused probing microwave beams in Doppler reflectometry on ITER-scale devices is discussed.     

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood.

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is a disorder of fatty acid catabolism, with autosomal recessive inheritance. The disease is characterized by episodic illness associated with potentially fatal hypoglycemia and has a relatively high frequency. A rapid and reliable method for the diagnosis of MCAD deficiency is highly desirable. Analysis of specific acylcarnitines was performed by isotope-dilution tandem mass spectrometry on plasma or whole blood samples from 62 patients with MCAD deficiency. Acylcarnitines were also analyzed in 42 unaffected relatives of patients with MCAD deficiency and in other groups of patients having elevated plasma C8 acylcarnitine, consisting of 32 receiving valproic acid, 9 receiving medium-chain triglyceride supplement, 4 having multiple acyl-coenzyme A dehydrogenase deficiency, and 8 others with various etiologies. Criteria for the unequivocal diagnosis of MCAD deficiency by acylcarnitine analysis are an elevated C8-acylcarnitine concentration (> 0.3 microM), a ratio of C8/C10 acylcarnitines of > 5, and lack of elevated species of chain length > C10. These criteria were not influenced by clinical state, carnitine treatment, or underlying genetic mutation, and no false-positive or false-negative results were obtained. The same criteria were also successfully applied to profiles from neonatal blood spots retrieved from the original Guthrie cards of eight patients. Diagnosis of MCAD deficiency can therefore be made reliably through the analysis of acylcarnitines in blood, including presymptomatic neonatal recognition. Tandem mass spectrometry is a convenient method for fast and accurate determination of all relevant acylcarnitine species.     

The International Joint Experiment ISTTOK

The 3rd International Joint Experiment has been carried out on ISTTOK following the last RUSFD (technical meeting on Research Using Small Fusion Devices) conference, held at Lisbon, in the scope of the IAEA Coordinated Research Project. This program has allowed a great knowledge interchange among the “small” fusion devices community and, in particular, in the development of common work-programs. This communication gives an overview of the impact of such activities. The JE have proved to be a very useful applied forum to share knowledge and to initiate young scientists in some fields of tokamak operation and diagnostics. Many of the ISTTOK 2008 relevant results were obtained under this scope.     

Small-angle scattering of an extraordinary wave near the upper hybrid resonance

The small-angle scattering of an extraordinary wave by plasma density fluctuations near the upper hybrid resonance is analyzed. It is shown that the efficiency of the small-angle scattering increases markedly as the upper hybrid resonance is approached. The power lost by the probing wave is calculated as a function of distance from the upper hybrid resonance, the parameters of the wavenumber spectrum of density fluctuations, and plasma parameters. The estimates obtained indicate that small-angle scattering, first, may have a strong impact on the experimental results obtained from the enhanced-scattering diagnostic and, second, may be the main cause of the broadening of the frequency spectrum of a signal recorded by this diagnostic technique.     

Incoherent Scattering of Electromagnetic Waves by Langmuir Fluctuations Trapped in a Plasma Density Well

Incoherent scattering of a probing wave by Langmuir fluctuations trapped and enhanced near a local minimum of the electron density (plasma density well) in plasma with a parabolic density profile is considered. Steady-state amplitudes of fluctuations are calculated for arbitrary velocity distribution functions of plasma particles with allowance for electron collisions. It is shown that quasi-periodic oscillations with two characteristic scales can be present in the spectrum of the plasma line. The smaller scale is due to the wellknown effect of discretization of the spectrum of Langmuir fluctuations in a plasma density well. The larger scale is associated with the generation of scattered waves in two spatial regions and subsequent interference of these waves at the exit from the density well. Oscillations with this scale are more stable under unsteady plasma conditions and can be more often observed in experiments. The results of this work can be used to experimentally determine the plasma parameters, such as the electron collision frequency and the size and lifetime of the plasma density well.     

Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex

The crystal structure of the human electron transferring flavoprotein (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF.MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD.ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.     

Estimates of the local parameters of plasma density fluctuations by reflectometry measurements

The question is considered of how to estimate the parameters of local plasma density fluctuations from reflectometry measurements made by probing the plasma with an extraordinary electromagnetic wave. In the geometrical-optics approximation, a formula is derived that relates the fluctuation amplitude of the phase of the reflected signal to the amplitude of local plasma density fluctuations and the range of its applicability is considered. The spectral sensitivity of reflectometry measurements in a reflection region of finite dimensions to poloidal perturbations with wavenumbers k _⊥ ? k ₀ is estimated by the phase-screen method, and the expressions obtained are compared with the results of numerical simulations. Based on the relationships derived, an algorithm is proposed for recovering the amplitude of the local plasma density fluctuations from the fluctuations in the reflected reflectometer signal. The results obtained are compared with the results of the full-wave simulations of the reflection of microwaves from a turbulent plasma. Finally, an example is given of how to recover the data on the amplitude of the local plasma density fluctuations in the T-10 tokamak plasma.     

Studies of fluctuations in the high-temperature plasma of modern stellarators by the microwave scattering technique

Microwave scattering diagnostics are described that allow direct measurements of the turbulent processes in the high-temperature plasma of magnetic confinement systems. The first physical results are presented from fluctuation measurements carried out in 2000–2001 in three stellarators: L-2M (Institute of General Physics, Moscow), LHD (National Institute of Fusion Science, Toki), and TJ-II (CIEMAT, Madrid). Plasma density fluctuations in the axial (heating) regions of the L-2M and LHD stellarators were measured from microwave scattering at the fundamental harmonic of the heating gyrotron radiation. In the TJ-II stellarator, a separate 2-mm microwave source was used to produce a probing beam; the measurements were performed at the middle of the plasma radius. Characteristic features of fluctuations, common for all three devices, are revealed by the methods of statistical and spectral analysis. These features are the wide frequency Fourier and wavelet spectra, autocorrelation functions with slowly decreasing tails, and non-Gaussian probability distributions of the magnitudes and the increments in the magnitude of fluctuations. Observations showed the high level of coherence between turbulent fluctuations in the central region and at the edge of the L-2M plasma. The drift-dissipative instability and the instability driven by trapped electrons are examined as possible sources of turbulence in a high-temperature plasma.     

MHD diagnostics in the T-11M tokamak

An MHD diagnostic system for investigating the dynamics of disruption and the preceding phase of the discharge in the T-11M tokamak is described. This system makes it possible to study the structure of magnetic fluctuations in the plasma column. The diagnostic system includes a set of magnetic pick-up loops (Mirnov coils) arranged in several poloidal cross sections of the tokamak, a data acquisition system that provides synchronous recording of Mirnov coil signals, a synchronization system for triggering the data acquisition system during a disruption, and a system for processing and representation of the experimental data on magnetic fluctuations in the plasma column. Examples of how the MHD diagnostic system operates in the T-11M tokamak are presented.     

Three RFLPs defining a haplotype associated with the common mutation in human medium-chain acyl-CoA dehydrogenase (MCAD) deficiency occur in Alu repeats.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common inborn error of fatty-acid oxidation and may cause sudden infant death. Previous studies revealed that (i) homozygosity for an A-to-G mutation at nucleotide 985 of the mRNA coding region (A985G) is an extremely common cause of MCAD deficiency and (ii) MCAD deficiency is strongly associated with a particular haplotype for RFLPs for BanII, PstI, and TaqI. TaqI allele 2 is always associated with the A985G mutation in human MCAD deficiency. In this study, we have delineated the molecular basis of the RFLPs for PstI, BamHI, and TaqI in the human MCAD gene. Our results prove that the three RFLPs are caused by point mutations in the 8 kb of DNA encompassing exons 8-10 of the human MCAD gene. The TaqI polymorphism is caused by a C-to-A substitution 392 bp upstream of the exon 8, and the PstI and BamHI polymorphisms are due to T-to-C and G-to-A substitutions, respectively, which are 727 and 931 bp downstream of exon 10 respectively. All three RFLPs lie within Alu repetitive sequences. Comparison of intronic sequences immediately following exon 10 from two normal individuals with different haplotypes showed that this region contains densely packed Alu repeats and is highly polymorphic. Our results are consistent both with a founder effect as the cause of the high prevalence of a single (A985G) mutation in MCAD deficiency and with its association with a particular haplotype for these intragenic RFLPs.     

Emission of low-frequency electromagnetic waves by a short laser pulse propagating in a plasma with density fluctuations

It is shown that a short laser pulse propagating in a plasma with electron density fluctuations can emit electromagnetic waves with frequencies much lower than the laser carrier frequency. Emissions with frequencies close to the plasma frequency and the doubled plasma frequency in a nonisothermal plasma, as well as emission generated in a turbulent plasma, are examined. The effects in question are related to the transformation of the laser pulse wakefield into electromagnetic radiation by electron density fluctuations. The phenomenon under study opens new possibilities for diagnostics of both plasma fields excited by laser pulses and electron density fluctuations in a plasma.     

Recovery of the characteristics of plasma turbulence from the radial correlation backscattering diagnostics

Signals of the backscattering radial correlation Doppler diagnostics of plasma density fluctuations in the presence of the cutoff of the probing wave are analyzed theoretically with allowance for the curvature of magnetic surfaces. The scattering of the probing electromagnetic wave is considered in the linear (Born) approximation with respect to the amplitude of fluctuations. Using the Wentzel?Kramers?Brillouin approach, analytical expressions for the scattered signal and the correlation function of two scattered signals corresponding to oblique probing at different frequencies are derived. A criterion is obtained for the tilt angle of the antenna pattern at which the two-point turbulence correlation function can be measured directly. A method is proposed to recover the spectrum of plasma density fluctuations from the data on the radial wavenumbers even if this criterion is violated.     

Binding of the human "electron transferring flavoprotein" (ETF) to the medium chain acyl-CoA dehydrogenase (MCAD) involves an arginine and histidine residue

The interaction between the "electron transferring flavoprotein" (ETF) and medium chain acyl-CoA dehydrogenase (MCAD) enables successful flavin to flavin electron transfer, crucial for the beta-oxidation of fatty acids. The exact biochemical determinants for ETF binding to MCAD are unknown. Here we show that binding of human ETF, to MCAD, was inhibited by 2,3-butanedione and diethylpyrocarbonate (DEPC) and reversed by incubation with free arginine and hydroxylamine respectively. Spectral analyses of native ETF vs modified ETF suggested that flavin binding was not affected and that the loss of ETF activity with MCAD involved modification of one ETF arginine residue and one ETF histidine residue respectively. MCAD and octanoyl-CoA protected ETF against inactivation by both 2,3-butanedione and DEPC indicating that the arginine and histidine residues are present in or around the MCAD binding site. Comparison of exposed arginine and histidine residues among different ETF species, however, indicates that arginine residues are highly conserved but that histidine residues are not. These results lead us to conclude that this single arginine residue is essential for the binding of ETF to MCAD, but that the single histidine residue, although involved, is not.     

Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: Data from a cohort study

ABSTRACT: BACKGROUND: Since the introduction of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency in population newborn bloodspot screening (NBS) programs, subjects have been identified with variant ACADM (gene encoding MCAD enzyme) genotypes that have never been identified in clinically ascertained patients. It could be hypothesised that residual MCAD enzyme activity can contribute in risk stratification of subjects with variant ACADM genotypes. METHODS: We performed a retrospective cohort study of all patients identified upon population NBS for MCAD deficiency in the Netherlands between 2007-2010. Clinical, molecular, and enzymatic data were integrated. RESULTS: Eighty-four patients from 76 families were identified. Twenty-two percent of the subjects had a variant ACADM genotype. In patients with classical ACADM genotypes, residual MCAD enzyme activity was significantly lower (median 0%, range 0-8%) when compared to subjects with variant ACADM genotypes (range 0-63%; 4 cases with 0%, remainder 20-63%). Patients with (fatal) neonatal presentations before diagnosis displayed residual MCAD enzyme activities <1%. After diagnosis and initiation of treatment, residual MCAD enzyme activities <10% were associated with an increased risk of hypoglycaemia and carnitine supplementation. The prevalence of MCAD deficiency upon screening was 1/8,750 (95% CI 1/7,210-1/11,130). CONCLUSIONS: Determination of residual MCAD enzyme activity improves our understanding of variant ACADM genotypes and may contribute to risk stratification. Subjects with variant ACADM genotypes and residual MCAD enzyme activities <10% should be considered to have the same risks as patients with classical ACADM genotypes. Parental instructions and an emergency regimen will remain principles of the treatment in any type of MCAD deficiency, as the effect of intercurrent illness on residual MCAD enzyme activity remains uncertain. There are, however, arguments in favour of abandoning the general advice to avoid prolonged fasting in subjects with variant ACADM genotypes and 10% residual MCAD enzyme activity.     

Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is one of the most common recessively inherited metabolic diseases in man. We have studied fibroblast cultures obtained from three patients with MCAD deficiency by sequencing the entire coding region of MCAD mRNA. A single A to G nucleotide replacement which resulted in lysine329-to-glutamic acid329 substitution of the MCAD protein was identified in all cultures. Furthermore, this point mutation was present in 91% (31 of 34) of mutant MCAD alleles, indicating that the majority of cases with MCAD deficiency are caused by this type of mutation.     

Binding of the Human “Electron Transferring Flavoprotein” (ETF) to the Medium Chain Acyl-CoA Dehydrogenase (MCAD) Involves an Arginine and Histidine Residue

The interaction between the “electron transferring flavoprotein” (ETF) and medium chain acyl-CoA dehydrogenase (MCAD) enables successful flavin to flavin electron transfer, crucial for the β-oxidation of fatty acids. The exact biochemical determinants for ETF binding to MCAD are unknown. Here we show that binding of human ETF, to MCAD, was inhibited by 2,3-butanedione and diethylpyrocarbonate (DEPC) and reversed by incubation with free arginine and hydroxylamine respectively. Spectral analyses of native ETF vs modified ETF suggested that flavin binding was not affected and that the loss of ETF activity with MCAD involved modification of one ETF arginine residue and one ETF histidine residue respectively. MCAD and octanoyl-CoA protected ETF against inactivation by both 2,3-butanedione and DEPC indicating that the arginine and histidine residues are present in or around the MCAD binding site. Comparison of exposed arginine and histidine residues among different ETF species, however, indicates that arginine residues are highly conserved but that histidine residues are not. These results lead us to conclude that this single arginine residue is essential for the binding of ETF to MCAD, but that the single histidine residue, although involved, is not.     

A rare disease-associated mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene changes a conserved arginine, previously shown to be functionally essential in short-chain acyl-CoA dehydrogenase (SCAD)

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a serious and potentially fatal inherited defect in the β-oxidation of fatty acids. Approximately 80% of patients with MCAD deficiency are homozygous for a single disease-causing mutation (G985). The remaining patients (except for a few cases worldwide) are compound heterozygous with G985 in one allele. By sequencing of cloned PCR-amplified MCAD cDNA from a G985 compound heterozygous patient, we identified a C-to-T transition at position 157 as the only change in the entire coding sequence of the non-G985 allele. The presence of the T157 mutation was verified in genomic DNA from the patient and her mother by a PCR-based assay. The mutation changes a conserved arginine at position 28 (R28C) of the mature MCAD protein. The effect of the T157 mutation on MCAD protein was investigated by expression of mutant MCAD cDNA in COS-7 cells. On the basis of knowledge about the three-dimensional structure of the MCAD protein, we suggest that the mutation destroys a salt bridge between arginine²⁸ and glutamate⁸⁶, thereby affecting the formation of enzymatically active protein. Twenty-two additional families with compound heterozygous patients were tested in the PCR-based assay. The T157 mutation was identified in one of these families, which had an MCAD-deficient child who died unexpectedly in infancy. Our results indicate that the mutation is rare. It is, however, noteworthy that a homologous mutation has previously been identified in the short-chain acyl-CoA dehydrogenase (SCAD) gene of a patient with SCAD deficiency, suggesting that the conserved arginine is crucial for formation of active enzyme in the straight-chain acyl-CoA dehydrogenases.     

Disease-causing Mutations in Exon 11 of the Medium-Chain Acyl-CoA Dehydrogenase Gene

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most commonly recognized defect of the mitochondrial β-oxidation in humans. It is a potentially fatal, autosomal recessive inherited defect. Most patients with MCAD deficiency are homozygous for a single disease-causing mutation (G985), causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD. Only seven non-G985 mutations, all of which are rare, have been reported. Because the G985 mutation and three of the non-G985 mutations are located in exon 11, it has been suggested that this exon may be a mutational hot spot. Here we describe the results from sequence analysis of exon 11 and part of the flanking introns from 36 compound heterozygous patients with MCAD deficiency. We have identified four previously unknown disease-causing mutations (M301T, S311R, R324X, and E359X) and two silent mutations in exon 11. Our results show that exon 11 is not especially mutation prone. We demonstrate that two of the identified disease-causing mutations can be detected by restriction enzyme digestion of the PCR product from the assay for the G985 mutation, a discovery that makes this assay even more useful than before. On the basis of expression of wild-type and mutant MCAD protein in COS-7 cells, we show that the identified mutations abolish MCAD enzyme activity and that they therefore must be disease causing. The M301T, S311R, and K304E mutations are located in helix H, which makes up part of the dimer-dimer interface of the MCAD tetramer. On the basis of the three-dimensional structure of MCAD and the results from the COS-7 expression experiments, we speculate that the primary effect of the M301T and S311R mutations is on correct folding/tetramer assembly, as it has previously been observed for the K304E mutation.     

Generalized scale invariance and log-Poisson statistics for turbulence in the scrape-off-layer plasma in the T-10 tokamak

Results are presented from experimental observations of the statistical properties of scrape-off-layer plasma turbulence in the T-10 tokamak. The experimentally observed fluctuations in the fluxes and plasma density are intermittent in nature and obey a non-Gaussian statistics. The generalized property of plasma turbulence is its scale invariance. The experimental scalings for the moments of the distribution function of the difference in the amplitudes of fluctuations in the fluxes and plasma density are described by the log-Poisson model of strong turbulence. The self-similarity properties of turbulence that are associated with the topology of dissipative structures are investigated.