Progressive impairment of CaV1.1 function in the skeletal muscle of mice expressing a mutant type 1 Cu/Zn superoxide dismutase (G93A) linked to amyotrophic lateral sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that is typically fatal within 3–5 years of diagnosis. While motoneuron death is the defining characteristic of ALS, the events that underlie its pathology are not restricted to the nervous system. In this regard, ALS muscle atrophies and weakens significantly before presentation of neurological symptoms. Since the skeletal muscle L-type Ca2+ channel (CaV1.1) is a key regulator of both mass and force, we investigated whether CaV1.1 function is impaired in the muscle of two distinct mouse models carrying an ALS-linked mutation. Methods: We recorded L-type currents, charge movements, and myoplasmic Ca2+ transients from dissociated flexor digitorum brevis (FDB) fibers to assess CaV1.1 function in two mouse models expressing a type 1 Cu/Zn superoxide dismutase mutant (SOD1G93A). Results: In FDB fibers obtained from “symptomatic” global SOD1G93A mice, we observed a substantial reduction of SR Ca2+ release in response to depolarization relative to fibers harvested from age-matched control mice. L-type current and charge movement were both reduced by ~40 % in symptomatic SOD1G93A fibers when compared to control fibers. Ca2+ transients were not significantly reduced in similar experiments performed with FDB fibers obtained from “early-symptomatic” SOD1G93A mice, but L-type current and charge movement were decreased (~30 and ~20 %, respectively). Reductions in SR Ca2+ release (~35 %), L-type current (~20 %), and charge movement (~15 %) were also observed in fibers obtained from another model where SOD1G93A expression was restricted to skeletal muscle. Conclusions: We report reductions in EC coupling, L-type current density, and charge movement in FDB fibers obtained from symptomatic global SOD1G93A mice. Experiments performed with FDB fibers obtained from early-symptomatic SOD1G93A and skeletal muscle autonomous MLC/SOD1G93A mice support the idea that events occurring locally in the skeletal muscle contribute to the impairment of CaV1.1 function in ALS muscle independently of innervation status

Ensemble prediction for nowcasting with a convection-permitting model - II: forecast error statistics

A 24-member ensemble of 1-h high-resolution forecasts over the Southern United Kingdom is used to study short-range forecast error statistics. The initial conditions are found from perturbations from an ensemble transform Kalman filter. Forecasts from this system are assumed to lie within the bounds of forecast error of an operational forecast system. Although noisy, this system is capable of producing physically reasonable statistics which are analysed and compared to statistics implied from a variational assimilation system. The variances for temperature errors for instance show structures that reflect convective activity. Some variables, notably potential temperature and specific humidity perturbations, have autocorrelation functions that deviate from 3-D isotropy at the convective-scale (horizontal scales less than 10 km). Other variables, notably the velocity potential for horizontal divergence perturbations, maintain 3-D isotropy at all scales. Geostrophic and hydrostatic balances are studied by examining correlations between terms in the divergence and vertical momentum equations respectively. Both balances are found to decay as the horizontal scale decreases. It is estimated that geostrophic balance becomes less important at scales smaller than 75 km, and hydrostatic balance becomes less important at scales smaller than 35 km, although more work is required to validate these findings. The implications of these results for high-resolution data assimilation are discussed

Dynamical Drivers of the Local Wind Regime in a Himalayan Valley

Understanding the local valley wind regimes in the Hindu-Kush Karakoram Himalaya is vital for future predictions of the glacio-hydro-meteorological system. Here the Weather Research and Forecasting model is employed at a resolution of 1 km to investigate the forces driving the local valleywind regime in a river basin in the Nepalese Himalaya, during July 2013 and January 2014. Comparing withobservations shows that the model represents the diurnal cycle of the winds well, with strong daytime up-valley winds and weak nighttime winds in both months. A momentum budget analysis of the model output shows that in the summer run the physical drivers of the near-surface valley wind also have a clear diurnal cycle, and are dominated by the pressure gradient, advection, and turbulent vertical mixing,as well as a nonphysical numerical diffusion term. By contrast, the drivers in the winter run have a less consistent diurnal cycle. In both months, the pressure gradient, advection, numerical diffusion, and Coriolis terms dominate up to 5,000 m above the ground. The drivers are extremely variable over the valley, and also influenced by the presence of glaciers. When glaciers are removed from the model in the summer run, the wind continues further up the valley, indicating how the local valley winds might respond to future glacier shrinkage. The spatial variability of the drivers over both months is consistent with the complex topography in the basin, which must therefore be well represented in weather and regional climate models to generate accurate output

Solar Wind Sputtering of Lunar Soil Analogs: The Effect of Ionic Charge and Mass

In this contribution we report sput-tering measurements of anorthite, an analog material representative of the lunar highlands, by singly and multicharged ions representative of the solar wind. The ions investigated include protons, as well as singly and multicharged Ar ions (as proxies for the heavier solar wind constituents), in the charge state range +1 to +9, and had a fixed solar-wind-relevant impact velocity of approximately 310 km/s or 500 eV/ amu. The goal of the measurements was to determine the sputtering contribution of the heavy, multicharged minority solar wind constituents in comparison to that due to the dominant H+ fraction

Detection of fast radio transients with multiple stations: a case study using the Very Long Baseline Array

Recent investigations reveal an important new class of transient radio phenomena that occur on sub-millisecond timescales. Often transient surveys' data volumes are too large to archive exhaustively. Instead, an on-line automatic system must excise impulsive interference and detect candidate events in real-time. This work presents a case study using data from multiple geographically distributed stations to perform simultaneous interference excision and transient detection. We present several algorithms that incorporate dedispersed data from multiple sites, and report experiments with a commensal real-time transient detection system on the Very Long Baseline Array (VLBA). We test the system using observations of pulsar B0329+54. The multiple-station algorithms enhanced sensitivity for detection of individual pulses. These strategies could improve detection performance for a future generation of geographically distributed arrays such as the Australian Square Kilometre Array Pathfinder and the Square Kilometre Array.Comment: 12 pages, 14 figures. Accepted for Ap

A Sample of Very Young Field L Dwarfs and Implications for the Brown Dwarf "Lithium Test" at Early Ages

Using a large sample of optical spectra of late-type dwarfs, we identify a subset of late-M through L field dwarfs that, because of the presence of low-gravity features in their spectra, are believed to be unusually young. From a combined sample of 303 field L dwarfs, we find observationally that 7.6+/-1.6% are younger than 100 Myr. This percentage is in agreement with theoretical predictions once observing biases are taken into account. We find that these young L dwarfs tend to fall in the southern hemisphere (Dec < 0 deg) and may be previously unrecognized, low-mass members of nearby, young associations like Tucana-Horologium, TW Hydrae, beta Pictoris, and AB Doradus. We use a homogeneously observed sample of roughly one hundred and fifty 6300-10000 Angstrom spectra of L and T dwarfs taken with the Low-Resolution Imaging Spectrometer at the W. M. Keck Observatory to examine the strength of the 6708-A Li I line as a function of spectral type and further corroborate the trends noted by Kirkpatrick et al. (2000). We use our low-gravity spectra to investigate the strength of the Li I line as a function of age. The data weakly suggest that for early- to mid-L dwarfs the line strength reaches a maximum for a few 100 Myr, whereas for much older (few Gyr) and much younger (<100 Myr) L dwarfs the line is weaker or undetectable. We show that a weakening of lithium at lower gravities is predicted by model atmosphere calculations, an effect partially corroborated by existing observational data. Larger samples containing L dwarfs of well determined ages are needed to further test this empirically. If verified, this result would reinforce the caveat first cited in Kirkpatrick et al. (2006) that the lithium test should be used with caution when attempting to confirm the substellar nature of the youngest brown dwarfs.Comment: 73 pages with 22 figures; to appear in ApJ (Dec 20, 2008, v689n2 issue