ALS-associated mutant SOD1<Superscript>G93A</Superscript> causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes

Background  

Amyotrophic lateral sclerosis (ALS) is an age-dependent neurodegenerative disease that causes motor neuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause for the familial form of this disease. Transgenic mice expressing mutant SOD1 develop age-dependent motor neuron degeneration, skeletal muscle weakness, paralysis and death similar to humans. The mechanism whereby mutant SOD1 induces motor neuron degeneration is not understood but widespread mitochondrial vacuolation has been observed during early phases of motor neuron degeneration. How this vacuolation develops is not clear, but could involve autophagic vacuolation, mitochondrial permeability transition (MPT) or uncharacterized mechanisms. To determine which of these possibilities are true, we examined the vacuolar patterns in detail in transgenic mice expressing mutant SOD1^G93A.     

First inelastic neutron scattering studies on thin free standing polymer films

Glass transition studies in free standing polymer films have revealed values of the transition temperature, T(g), which were substantially reduced below the bulk for sufficiently thin films. Here we report on the preparation of two stacks of free standing polystyrene films: 70 films with a thickness of h approximately 107 nm and 140 films with h approximately 55 nm with equivalent total sample thicknesses of approximately 7.5 microm. We have performed the first measurements on such samples using inelastic neutron scattering, and demonstrate that inelastic neutron scattering experiments, performed on the time-of-flight spectrometer IN6 and the backscattering spectrometer IN16 at the Institut Laue-Langevin, are feasible.     

First inelastic neutron scattering studies on thin free standing polymer films

Intermolecular coupling plays an important role in determining the dynamics and the mobility of polymeric and non-polymeric glass-formers. The breadth of the dispersion is an indicator of the intermolecular coupling strength. The coupling model relates intermolecular coupling through the breadth of the dispersion to the dynamics of bulk glass-formers. When a glass-former is confined in nanometer pores or in thin films and if there is absence of chemical and physical interactions with the wall, intermolecular coupling is reduced, resulting in an increase of mobility. The coupling model is used to account for such changes of relaxation time of 1) ortho-terphenyl and poly(dimethyl siloxane) confined in nanometer pores, 2) polymer thin film confined between two impenetrable walls from Monte Carlo simulation, and 3) polymer film confined by perfectly smooth and purely repulsive potential acting on the repeat units from molecular-dynamics simulation. The model continues to explain the opposite effects observed when there is an increase of intermolecular coupling due to the presence of chemical or physical interaction with the walls.Received: 1 January 2003, Published online: 8 October 2003PACS: 64.70.Pf Glass transitions - 68.60.Bs Mechanical and acoustical properties - 36.20.-r Macromolecules and polymer molecules     

The Sampling Theorem and Several Equivalent Results in Analysis

First we show that several fundamental results on functions from theBernstein spaces (such as Bernstein's inequality andthe reproducing formula) can be deduced from a weak form of the classicalsampling theorem. In §3 we discuss the mutual equivalence of thesampling theorem, the derivative sampling theorem and a harmonic functionsampling theorem. In §§4–6 we discuss connections between thesampling theorem and various important results in complex analysis andFourier analysis. Our considerations include Cauchy's integral formula,Poisson's summation formula, a Gaussian integral, certain properties ofweighted Hermite polynomials, Plancherel's theorem, the maximum modulusprinciple, and the Phragmén–Lindelöf principle.     

The precision of determinations of zinc content of food

Seven different types of foodstuff (containing 3-100 ppm Zn) were each analysed for zinc by colorimetry, polarography and atomic-absorption spectroscopy. All the techniques yielded similar values for the zinc content of a given sample, but atomic-absorption spectroscopy had a smaller average coefficient of variation.     

Quasielastic scattering of neutrons from freely jointed polymer chains in dilute solutions

Starting with Kirkwood's Fokker–Planck equation for the polymer configuration-space distribution function and using the Zwanzig–Mori projection operator technique we have calculated the scattering law S_(q,w) for a freely jointed model polymer chain in a dilute solution. When memory effects are neglected, the theory predicts a Lorentzian for S_(q,w) with a halfwidth Ω_(q), which we have determined as a function of the momentum transfer q for all values of q. The results are compared with recent neutron scattering experiments on deuterated polytetrahydrofuran and polystyrene in dilute solution in CS₂. It is found that the observed q dependence of Ω(q) is represented satisfactorily by the present theory with a bond length b of about 6.3 Å for polystyrene and 3.8 Å for polytetrahydrofuran, and a friction coefficient ζ = 4πη0b where η₀ is the viscosity of the solvent.     

dHvA measurements of long range strain effects due to lattice dislocations in copper

Lattice dislocations have been shown to produce a factor of 10³ greater dHvA scattering temperature than an estimate from resistivity. The magnitude of this discrepancy is explained by a first principles phase smearing calculation, and is due to the sensitivity of the quantum oscillations to small angle scattering by the long range strain field. Breaking the cubic symmetry by introducing a forest of edge dislocations allows a test of the sensitivity of previously equivalent neck orbits to the relative orientation with respect to the dislocation lines. Both magnitudes and anisotropy agree with the theory. It is shown how to separate these effects from mosaic structure effects also present in these deformed crystals. In a separate experiment, neutron irradiation was used to produce dislocation loops. Here, the dHvA scattering is observed to be of the same order as resistivity scattering, due to the cancellation of the long range dislocation strain field in the loop geometry.     

Summation bandwidths at threshold in normal and hearing-impaired listeners

The bandwidths for summation at threshold were measured for subjects with normal hearing and subjects with sensorineural hearing loss. Thresholds in quiet and in the presence of a masking noise were measured for complex stimuli consisting of 1 to 40 pure-tone components spaced 20 Hz apart. The single component condition consisted of a single pure tone at 1100 Hz; additional components were added below this frequency, in a replication of the G?ssler [Acustica 4, 408-414 (1954)] procedure. For the normal subjects, thresholds increased approximately 3 dB per doubling of bandwidth for signal bandwidths exceeding the critical bandwidth. This slope was less for the hearing-impaired subjects. Summation bandwidths, as estimated from two-line fits, were wider for the hearing-impaired than for the normal subjects. These findings provide evidence that hearing-impaired subjects integrate sound energy over a wider-than-normal frequency range for the detection of complex signals. A second experiment used stimuli similar to those of Spiegel [J. Acoust. Soc. Am. 66, 1356-1363 (1979)], and added components both above and below the frequency of the initial component. Using these stimuli, the slope of the threshold increase beyond the critical bandwidth was approximately 1.5 dB per doubling of bandwidth, thus replicating the Spiegel (1979) experiment. It is concluded that the differences between the G?ssler (1954) and Spiegel (1979) studies were due to the different frequency content of the stimuli used in each study. Based upon the present results, it would appear that the slope of threshold increase is dependent upon the direction of signal expansion, and the size of the critical bands into which the signal is expanded.     

Gender differences in vocal fold contact computed from electroglottographic signals: the influence of measurement criteria

EGGW is a phonatory parameter that can be derived from electroglottographic (EGG) signals and used to infer the relative degree of vocal fold contact. Vocal fold models predict that men will exhibit medial bulging of their vocal folds during phonation but women will not. These models lead us to expect gender differences in the magnitude of EGGW. Nevertheless, significant gender differences in EGGW for adults with normal voices have not been documented in previous studies when EGGW was computed from criterion lines placed at 25%-40% of the amplitude of the uninverted EGG wave form. We hypothesized that EGGW would better reflect gender differences in vocal fold adductory patterns if EGGW was computed from portions of the wave form that were associated with more vocal fold contact. EGGW was measured for seven men and seven women with normal voices. When EGGW was computed from segments of the wave form that were associated with relatively greater vocal fold contact (i.e., using criterion levels of > or = 55%), findings were consistent with the gender-specific adductory patterns that have been proposed from vocal fold models. Guidelines for appropriate placement of criterion lines when computing EGGW are discussed.