Experimentally validated continuous-time repetitive control of non-minimum phase plants with a prescribed degree of stability

This paper considers the application of continuous-time repetitive control to non-minimum phase plants in a continuous-time model predictive control setting. In particular, it is shown how some critical performance problems associated with repetitive control of such plants can be avoided by use of predictive control with a prescribed degree of stability. The results developed are first illustrated by simulation studies and then through experimental tests on a non-minimum phase electro-mechanical system

Wavelength-independent coupler from fiber to an on-chip cavity, demonstrated over an 850nm span

A robust wide band (850 nm) fiber coupler to a whispering-gallery cavity with ultra-high quality factor is experimentally demonstrated. The device trades off ideality for broad-band, efficient input coupling. Output coupling efficiency can remain high enough for practical applications wherein pumping and power extraction must occur over very broad wavelength spans

Mice with endogenous TDP‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis

TDP-43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in vivo. Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects. TDP-43 gain-of-function effects in these mice reveal a novel category of splicing events controlled by TDP-43, referred to as "skiptic" exons, in which skipping of constitutive exons causes changes in gene expression. In vivo, this gain-of-function mutation in endogenous Tardbp causes an adult-onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain-of-function and skiptic exons in ALS patient-derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP-43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages. Keywords: ALS; cryptic exon; skiptic exon; splicing; TDP-4