Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic ...

Full waveform inversion (FWI) can generate high-resolution subsurface models, but often suffers from an objective function with local minima caused mainly by an absence of low frequencies in seismograms. These local minima cause cycle skipping when the initial model for FWI is far from the true model. To avoid cycle skipping, traveltime inversion is often used to compute initial models for FWI....

We provide a general notion of a Digital Derivative in 1−dimensional grids, which has real or integer-only versions. From any such masks, a family of masks called skipping masks are defined. We prove general results of multigrid convergence for skipping masks. We propose a few examples of digital derivative masks, including the now well-known binomial mask. The corresponding skipping masks auto...

The probability of skipping a word is influenced by its processing ease. For instance, a word that is predictable from the preceding context is skipped more often than an unpredictable word. A meta-analysis of studies examining this predictability effect reported effect sizes ranging from 0 to 13%, with an average of 8%. One study does not fit within this picture and reported 23% more skipping ...

BACKGROUND Antisense oligonucleotide-induced exon skipping is a promising approach for treatment of Duchenne muscular dystrophy (DMD). We have systemically administered an antisense phosphorodiamidate morpholino oligomer (PMO) targeting dystrophin exons 6 and 8 to a dog with canine X-linked muscular dystrophy in Japan (CXMD(J)) lacking exon 7 and achieved recovery of dystrophin in skeletal musc...

Deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) catabolism, has been linked to toxic side effects of 5-FU. The most prominent mutation of the DPD gene resulting in severe DPD deficiency is a G to A mutation in the GT 5'-splice recognition site of intron 14 (exon 14-skipping mutation). The corresponding mRNA lacks exon 14, and the enzymatic ...

Skipping of internal exons during removal of introns from pre-mRNA must be avoided for proper expression of most eukaryotic genes. Despite significant understanding of the mechanics of intron removal, mechanisms that ensure inclusion of internal exons in multi-intron pre-mRNAs remain mysterious. Using a natural two-intron yeast gene, we have identified distinct RNA-RNA complementarities within ...

Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing represso...