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A repeat expansion mutation in the C9orf72 gene is the leading known genetic cause of FTD and ALS. The C9orf72-ALS/FTD field has been plagued by a lack of reliable tools to monitor this genomic locus and its RNA and protein products. We have validated assays that quantify C9orf72 pathobiology at the DNA, RNA and protein levels using knock-out human iPSC lines as controls. Here we show that single-molecule sequencing can accurately measure the repeat expansion and faithfully report on changes to the C9orf72 locus in what has been a traditionally hard to sequence genomic region. This is of particular value to sizing and phasing the repeat expansion and determining changes to the gene locus after gene editing. We developed ddPCR assays to quantify two major C9orf72 transcript variants, which we validated by selective excision of their distinct transcriptional start sites. Using validated knock-out human iPSC lines, we validated 4 commercially available antibodies (of 9 tested) that were specific for C9orf72 protein quantification by Western blot, but none were specific for immunocytochemistry. We tested 15 combinations of antibodies against dipeptide repeat proteins (DPRs) across 66 concentrations using MSD immunoassay, and found two (against poly-GA and poly-GP) that yielded a 1.5-fold or greater signal increase in patient iPSC-motor neurons compared to knock-out control, and validated them in human postmortem and transgenic mouse brain tissue. Our validated DNA, RNA and protein assays are applicable to discovery research as well as clinical trials.

In conventional hexagonal InGaAlN multiple-quantum-well (MQW) (h-) light-emitting diodes (LEDs), carrier leakage from QWs is the main source of internal quantum efficiency (IQE) degradation without contributing to the LED efficiency droop. Our analysis based on the newly developed Open Boundary Quantum LED Simulator indicates that radiative recombination is hampered by the poor electron–hole wavefunction overlap induced by strong internal polarization for which QW carriers mostly recombine via Auger scattering rather than by radiative processes. By contrast, in non-polar h-LEDs, the IQE peak doubles its value compared to conventional h-LEDs while quenching the efficiency droop by 70% at current density of 100 A/cm2. Those effects are further enhanced in cubic InGaAlN MQW (c-) LEDs for which the IQE peak increases by an additional 30%, and the efficiency droop is further reduced by 80% compared to non-polar h-LEDs, thanks to the larger optical transition matrix element and the strong electron–hole wavefunction overlap in c-LEDs. Overall, a c-LED with a low efficiency droop of 3% at 100 A/cm2 is anticipated, paving a clear pathway toward ultimate solid-state lighting. [ABSTRACT FROM AUTHOR]

Superfluid 3He is a paradigm for odd-parity Cooper pairing, ranging from neutron stars to uranium-based superconducting compounds. Recently it has been shown that 3He, imbibed in anisotropic silica aerogel with either positive or negative strain, preferentially selects either the chiral A-phase or the time-reversal-symmetric B-phase. This control over basic order parameter symmetry provides a useful model for understanding imperfect unconventional superconductors. For both phases, the orbital quantization axis is fixed by the direction of strain. Unexpectedly, at a specific temperature Tx, the orbital axis flops by 90∘, but in reverse order for A and B-phases. Aided by diffusion limited cluster aggregation simulations of anisotropic aerogel and small angle X-ray measurements, we are able to classify these aerogels as either "planar" and "nematic" concluding that the orbital-flop is caused by competition between short and long range structures in these aerogels. When imbibed in an anisotropic silica aerogel, superfluid 3He undergoes a temperature-driven "orbital flop" transition, where the orbital quantization axis rotates by 90 degrees. Here, by simulating planar and nematic aerogel, M. D. Nguyen et al. show that the orbital flop transition is driven by the distinct large- and small-scale structures of the aerogel. [ABSTRACT FROM AUTHOR]