Versatile Genome Engineering Techniques Advance Human Ocular Disease Researches in Zebrafish

Over recent decades, zebrafish has been established as a sophisticated vertebrate model for studying human ocular diseases due to its high fecundity, short generation time and genetic tractability. With the invention of morpholino (MO) technology, it became possible to study the genetic basis and relevant genes of ocular diseases in vivo. Many genes have been shown to be related to ocular diseases. However, the issue of specificity is the major concern in defining gene functions with MO technology. The emergence of the first- and second-generation genetic modification tools zinc-finger nucleases (ZFNs) and TAL effector nucleases (TALENs), respectively, eliminated the potential phenotypic risk induced by MOs. Nevertheless, the efficiency of these nucleases remained relatively low until the third technique, the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, was discovered. This review highlights the application of multiple genome engineering techniques, especially the CRISPR/Cas9 system, in the study of human ocular diseases in zebrafish

Discovery of four gravitational lensing systems by clusters in the SDSS DR6

We report the discovery of 4 strong gravitational lensing systems by visual inspections of the Sloan Digital Sky Survey images of galaxy clusters in Data Release 6 (SDSS DR6). Two of the four systems show Einstein rings while the others show tangential giant arcs. These arcs or rings have large angular separations (>8") from the bright central galaxies and show bluer color compared with the red cluster galaxies. In addition, we found 5 probable and 4 possible lenses by galaxy clusters.Comment: 6 pages, 3 figures. Added referenc

Engineered zero-dispersion microcombs using CMOS-ready photonics

Normal group velocity dispersion (GVD) microcombs offer high comb line power and high pumping efficiency compared to bright pulse microcombs. The recent demonstration of normal GVD microcombs using CMOS-foundry-produced microresonators is an important step towards scalable production. However, the chromatic dispersion of CMOS devices is large and impairs generation of broadband microcombs. Here, we report the development of a microresonator in which GVD is reduced due to a couple-ring resonator configuration. Operating in the turnkey self-injection-locking mode, the resonator is hybridly integrated with a semiconductor laser pump to produce high-power-efficiency combs spanning a bandwidth of 9.9 nm (1.22 THz) centered at 1560 nm, corresponding to 62 comb lines. Fast, linear optical sampling of the comb waveform is used to observe the rich set of near-zero GVD comb behaviors, including soliton molecules, switching waves (platicons) and their hybrids. Tuning of the 20 GHz repetition rate by electrical actuation enables servo locking to a microwave reference, which simultaneously stabilizes the comb repetition rate, offset frequency and temporal waveform. This hybridly integrated system could be used in coherent communications or for ultra-stable microwave signal generation by two-point optical frequency division.Comment: 8 pages, 4 figure

Integrated turnkey soliton microcombs operated at CMOS frequencies

We experimentally discovered and theoretically explain a novel turnkey regime for operation of soliton microcombs, wherein a new operating point enables the direct access of the soliton state by simple turn-on of the pump laser

Chip-Based Laser with 1 Hertz Integrated Linewidth

Lasers with hertz-level linewidths on timescales up to seconds are critical for precision metrology, timekeeping, and manipulation of quantum systems. Such frequency stability typically relies on bulk-optic lasers and reference cavities, where increased size is leveraged to improve noise performance, but with the trade-off of cost, hand assembly, and limited application environments. On the other hand, planar waveguide lasers and cavities exploit the benefits of CMOS scalability but are fundamentally limited from achieving hertz-level linewidths at longer times by stochastic noise and thermal sensitivity inherent to the waveguide medium. These physical limits have inhibited the development of compact laser systems with frequency noise required for portable optical clocks that have performance well beyond conventional microwave counterparts. In this work, we break this paradigm to demonstrate a compact, high-coherence laser system at 1548 nm with a 1 s integrated linewidth of 1.1 Hz and fractional frequency instability less than 10$^{-14}$ from 1 ms to 1 s. The frequency noise at 1 Hz offset is suppressed by 11 orders of magnitude from that of the free-running diode laser down to the cavity thermal noise limit near 1 Hz$^2$/Hz, decreasing to 10$^{-3}$ Hz$^2$/Hz at 4 kHz offset. This low noise performance leverages wafer-scale integrated lasers together with an 8 mL vacuum-gap cavity that employs micro-fabricated mirrors with sub-angstrom roughness to yield an optical $Q$ of 11.8 billion. Significantly, all the critical components are lithographically defined on planar substrates and hold the potential for parallel high-volume manufacturing. Consequently, this work provides an important advance towards compact lasers with hertz-level linewidths for applications such as portable optical clocks, low-noise RF photonic oscillators, and related communication and navigation systems

Integrated turnkey soliton microcombs operated at CMOS frequencies

While soliton microcombs offer the potential for integration of powerful frequency metrology and precision spectroscopy systems, their operation requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components. Moreover, CMOS-rate microcombs, required in nearly all comb systems, have resisted integration because of their power requirements. Here, a regime for turnkey operation of soliton microcombs co-integrated with a pump laser is demonstrated and theoretically explained. Significantly, a new operating point is shown to appear from which solitons are generated through binary turn-on and turn-off of the pump laser, thereby eliminating all photonic/electronic control circuitry. These features are combined with high-Q $Si_3N_4$ resonators to fully integrate into a butterfly package microcombs with CMOS frequencies as low as 15 GHz, offering compelling advantages for high-volume production.Comment: Boqiang Shen, Lin Chang, Junqiu Liu, Heming Wang and Qi-Fan Yang contributed equally to this wor

Photonic chip-based low noise microwave oscillator

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low noise microwave signals are generated by the down-conversion of ultra-stable optical references using a frequency comb. Such systems, however, are constructed with bulk or fiber optics and are difficult to further reduce in size and power consumption. Our work addresses this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division. Narrow linewidth self-injection locked integrated lasers are stabilized to a miniature Fabry-P\'{e}rot cavity, and the frequency gap between the lasers is divided with an efficient dark-soliton frequency comb. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc/Hz at 100 Hz offset frequency that decreases to -135 dBc/Hz at 10 kHz offset--values which are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems

Integrated turnkey soliton microcombs

Optical frequency combs have a wide range of applications in science and technology. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators. Such soliton microcombs have been applied to spectroscopy, the search for exoplanets, optical frequency synthesis, time keeping and other areas. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits—as is required in nearly all comb systems—have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor Si₃N₄ resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production