Zonal mean and tidal dynamics from space: An empirical examination of aliasing and sampling issues

Interpretations of space-based measurements of atmospheric parameters in the mesosphere and thermosphere are complicated by large local-time variations at these altitudes. For this reason, satellite orbits are often preferred which precess through all local times one or more times per season. However, the local-time structure of the atmosphere is inherently non-stationary, which can lead to sampling and aliasing difficulties when attempting to deconvolve the measurements into zonal mean and tidal components. In the present study, hourly radar measurements of mesopause-region winds are used to form a mock data base which can be used to gain insight into implications of the aforementioned problems; the use of actual measurements introduces a realistic element of geophysical temporal variability. Assuming zonal symmetry (i.e., migrating tides superimposed on a zonal mean circulation), the radar measurements are sampled from the satellite perspective for orbital inclinations of 57° and 70°, and compared to the ground or true perspective. These comparisons provide realistic estimates of the errors to be expected when attempting to derive mean and tidal components from space-based measurements. For both diurnal and semidiurnal components, and the quoted satellite inclinations, acceptable errors (3–4m/srms) are obtained for data covering 24h local time (i.e., ascending plus descending nodes); the corresponding errors for single-node data (12h local-time coverage) are of order 8–11m/s, and therefore may not represent reliable estimates of the actual tidal components. There exist certain caveats in connection with the latter conclusion which are discussed

Global distribution and interannual variations of mesospheric and lower thermospheric neutral wind diurnal tide: 1. Migrating tide

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95689/1/jgra18975.pd

RPGR-associated retinal degeneration in human X-linked RP and a murine model

PURPOSE. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model. METHODS. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5–72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset. RESULTS. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. CONCLUSIONS. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy

Restoration of mutant bestrophin-1 expression, localisation and function in a polarised epithelial cell model

Autosomal recessive bestrophinopathy (ARB) is a retinopathy caused by mutations in the bestrophin-1 protein, which is thought to function as a Ca2+-gated Cl− channel in the basolateral surface of the retinal pigment epithelium (RPE). Using a stably transfected polarised epithelial cell model, we show that four ARB mutant bestrophin-1 proteins were mislocalised and subjected to proteasomal degradation. In contrast to the wild-type bestrophin-1, each of the four mutant proteins also failed to conduct Cl− ions in transiently transfected cells as determined by whole-cell patch clamp. We demonstrate that a combination of two clinically approved drugs, bortezomib and 4-phenylbutyrate (4PBA), successfully restored the expression and localisation of all four ARB mutant bestrophin-1 proteins. Importantly, the Cl− conductance function of each of the mutant bestrophin-1 proteins was fully restored to that of wild-type bestrophin-1 by treatment of cells with 4PBA alone. The functional rescue achieved with 4PBA is significant because it suggests that this drug, which is already approved for long-term use in infants and adults, might represent a promising therapy for the treatment of ARB and other bestrophinopathies resulting from missense mutations in BEST1

TIMED Doppler Interferometer: Overview and recent results

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94617/1/jgra18230.pd

Monthly mean climatology of the prevailing winds and tides in the Artic mesosphere/lower thermosphere

The Arctic MLT wind regime parameters measured at the ground-based network of MF and meteor radar stations (Andenes 69° N, Tromsø 70° N, Esrange 68° N, Dixon 73.5° N, Poker Flat 65° N and Resolute Bay 75° N) are discussed and compared with those observed in the mid-latitudes. The network of the ground-based MF and meteor radars for measuring winds in the Arctic upper mesosphere and lower thermosphere provides an excellent opportunity for study of the main global dynamical structures in this height region and their dependence from longitude. Preliminary estimates of the differences between the measured winds and tides from the different radar types, situated 125-273km apart (Tromsø, Andenes and Esrange), are provided. Despite some differences arising from using different types of radars it is possible to study the dynamical wind structures. It is revealed that most of the observed dynamical structures are persistent from year to year, thus permitting the analysis of the Arctic MLT dynamics in a climatological sense. The seasonal behaviour of the zonally averaged wind parameters is, to some extent, similar to that observed at the moderate latitudes. However, the strength of the winds (except the prevailing meridional wind and the diurnal tide amplitudes) in the Arctic MLT region is, in general, less than that detected at the moderate latitudes, decreasing toward the pole. There are also some features in the vertical structure and seasonal variations of the Arctic MLT winds which are different from the expectations of the well-known empirical wind models CIRA-86 and HWM-93. The tidal phases show a very definite longitudinal dependence that permits the determination of the corresponding zonal wave numbers. It is shown that the migrating tides play an important role in the dynamics of the Arctic MLT region. However, there are clear indications with the presence in some months of non-migrating tidal modes of significant appreciable amplitude

Delineation of Cohen Syndrome Following a Large-Scale Genotype-Phenotype Screen

Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The pleiotropic phenotype, combined with insufficient clinical data, often leads to an erroneous diagnosis and has led to confusion in the literature. Here, we report the results of a comprehensive genotype-phenotype study on the largest cohort of patients with Cohen syndrome assembled to date. We found 22 different COH1 mutations, of which 19 are novel, in probands identified by our diagnostic criteria. In addition, we identified another three novel mutations in patients with incomplete clinical data. By contrast, no COH1 mutations were found in patients with a provisional diagnosis of Cohen syndrome who did not fulfill the diagnostic criteria (“Cohen-like” syndrome). This study provides a molecular confirmation of the clinical phenotype associated with Cohen syndrome and provides a basis for laboratory screening that will be valuable in its diagnosis