In vivo genome editing via CRISPR/Cas9-mediated homology-independent targeted integration for Bietti crystalline corneoretinal dystrophy treatment.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive chorioretinal degenerative disease without approved therapeutic drugs. It is caused by mutations in CYP4V2 gene, and about 80% of BCD patients carry mutations in exon 7 to 11. Here, we apply CRISPR/Cas9 mediated homology-independent targeted integration (HITI)-based gene editing therapy in HEK293T cells, BCD patient derived iPSCs, and humanized Cyp4v3 mouse model (h-Cyp4v3mut/mut) using two rAAV2/8 vectors via sub-retinal administration. We find that sgRNA-guided Cas9 generates double-strand cleavage on intron 6 of the CYP4V2 gene, and the HITI donor inserts the carried sequence, part of intron 6, exon 7-11, and a stop codon into the DNA break, achieving precise integration, effective transcription and translation both in vitro and in vivo. HITI-based editing restores the viability of iPSC-RPE cells from BCD patient, improves the morphology, number and metabolism of RPE and photoreceptors in h-Cyp4v3mut/mut mice. These results suggest that HITI-based editing could be a promising therapeutic strategy for those BCD patients carrying mutations in exon 7 to 11, and one injection will achieve lifelong effectiveness.

Study on measurement of dispersive characteristics of higher order mode Lamb waves.

The dispersive characteristics of higher order mode Lamb waves (HOMLW) excited by interdigital transducers (IDT) are measured and analyzed, which are necessary for designing micro-sensor in ultrahigh frequency (UHF). A measurement system is set up, in which dispersive characteristics of HOMLW are obtained by the method of transform between frequency and time domains. The characteristics of amplitude-frequency and phase-frequency of Lamb wave are auto-measured by the system. By IFFT, the pulse response of the IDT device was obtained. Different modes were separated in time domain and dispersive curve of each mode is calculated by FFT. The best mode is chosen to design the micro-sensor in UHF. The phase velocity of HOMLW is greater than the surface wave (SAW) velocity and an oscillator in higher frequency can be made, so the absolute sensitivity of micro-sensor can be increased. In this paper, the dispersive characteristics of HOMLW excited by an IDT in a 127.86 degrees rotated Y-cut, X propagating lithium niobate plate is analyzed. An oscillator using a(13) mode is made, the phase velocity of which is measured about 19,652 m/s when h/lambda=0.94 (h=plate thickness, lambda=wavelength).

Active control of radiation from a piston set in a rigid sphere.

Active control of the sound radiated from a piston set in a rigid sphere with a set of control point sources around is considered in this paper, where the scattering sound field of the control sound from the rigid sphere has been taken into account to minimize the total radiated sound power. Analytic results of the sound power are obtained and numerical simulations show that it is possible to reduce the radiation from a small piston set in a rigid sphere similar to the size of a human head up to a certain frequency. It is found that the introduction of the scattering object makes significant differences from the active control without scattering objects. This being the case, the scattering object makes the active noise control easier. To increase the global reduction of sound-power output, the optimal number and locations of the control sources and the optimal number and locations of error sensors are discussed. Finally, experiments with one control source and one error sensor around a head simulator have been carried out to verify the simulation results.

Lattice form adaptive infinite impulse response filtering algorithm for active noise control.

In some situations of active noise control, infinite impulse response (IIR) filters are more suitable than finite impulse response (FIR) filters owing to the poles in the transfer function. A number of algorithms have been derived for applying IIR filters in active noise control; however, most of them use the direct form IIR filter structure, which faces the difficulties of checking stability and relatively slow convergence speed for noise composed of narrow-band components with large power disparity. To overcome these difficulties along with using the direct form IIR filters, a new adaptive algorithm is proposed in this paper, which uses and updates the lattice form adaptive IIR filter in an active noise control system. Full mathematical derivations of the proposed algorithm are presented, and the comparison between the proposed algorithm and the commonly used filtered-u LMS and filtered-v LMS algorithms shows the superiority of the proposed algorithm.