Investigating synthetic oligonucleotide targeting of miR31 in Duchenne muscular dystrophy

Exon-skipping via synthetic antisense oligonucleotides represents one of the most promising potential therapies for Duchenne muscular dystrophy (DMD), yet this approach is highly sequence-specific and thus each oligonucleotide is of benefit to only a subset of patients. The discovery that dystrophin mRNA is subject to translational suppression by the microRNA miR31, and that miR31 is elevated in the muscle of DMD patients, raises the possibility that the same oligonucleotide chemistries employed for exon skipping could be directed toward relieving this translational block. This approach would act synergistically with exon skipping where possible, but by targeting the 3’UTR it would further be of benefit to the many DMD patients who express low levels of in-frame transcript. We here present investigations into the feasibility of combining exon skipping with several different strategies for miR31-modulation, using both in vitro models and the mdx mouse (the classical animal model of DMD), and monitoring effects on dystrophin at the transcriptional and translational level. We show that despite promising results from our cell culture model, our in vivo data failed to demonstrate similarly reproducible enhancement of dystrophin translation, suggesting that miR31-modulation may not be practical under current oligonucleotide approaches. Possible explanations for this disappointing outcome are discussed, along with suggestions for future investigations

Experimental assessment of a computer program used in Space Shuttle orbiter entry heating analysis

A high temperature reusable surface insulation (HRSI) tile taken from the Space Shuttle orbiter was subjected to a nominal heating rate of 60 kW/sq m in the laboratory. The surface temperature response to this heating was measured and used as input to a computer program which computed the applied heating rate. The program is part of a software system that is used to infer convective heating rates to the orbiter thermal protection system during entry. The measured and computed heating rates are compared. Results confirm the applicability of this program to the determination of flight heat transfer rates from flight measured surface temperature data

Saturn orbiter mission study

A preliminary analysis of the important aspects of missions orbiting the planet Saturn is provided. Orbital missions to Saturn is given serious consideration for the 1980's, or after flybys by Pioneer 10/G and Mariner Jupiter-Saturn 1977. An attempt is made to characterize Saturn orbiters in detail so that comparisons with Jupiter missions can be made. The scientific objectives of Saturn exploration are grouped under four topics: (1) the atmosphere, (2) the magnetosphere, (3) the rings, and (4) the satellites

Wind-tunnel investigation of the aerodynamic pressures on the Apollo command module configuration

Wind tunnel study of aerodynamic pressures on Apollo command module configuratio

Ocean gravity and geoid determination

Gravity anomalies have been recovered in the North Atlantic and the Indian Ocean regions. Comparisons of 63 2 deg x 2 deg mean free air gravity anomalies recovered in the North Atlantic area and 24 5 deg x 5 deg mean free air gravity anomalies in the Indian Ocean area with surface gravimetric measurements have shown agreement to + or - 8 mgals for both solutions. Geoids derived from the altimeter solutions are consistent with altimetric sea surface height data to within the precision of the data, about + or - 2 meters

Inclusion of unsteady aerodynamics in longitudinal parameter estimation from flight data

A simple vortex system, used to model unsteady aerodynamic effects into the rigid body longitudinal equations of motion of an aircraft, is described. The equations are used in the development of a parameter extraction algorithm. Use of the two parameter-estimation modes, one including and the other omitting unsteady aerodynamic modeling, is discussed as a means of estimating some acceleration derivatives. Computer generated data and flight data, used to demonstrate the use of the parameter-extraction algorithm are studied