Mid-infrared spectroscopy with a broadly tunable thin-film lithium niobate optical parametric oscillator

Mid-infrared spectroscopy, an important and widespread technique for sensing molecules, has encountered barriers stemming from sources either limited in tuning range or excessively bulky for practical field use. We present a compact, efficient, and broadly tunable optical parametric oscillator (OPO) device surmounting these challenges. Leveraging a dispersion-engineered singly-resonant OPO implemented in thin-film lithium niobate-on-sapphire, we achieve broad and controlled tuning over an octave, from 1.5 to 3.3 microns by combining laser and temperature tuning. The device generates > 25 mW of mid-infrared light at 3.2 microns, offering a power conversion efficiency of 15% (45% quantum efficiency). We demonstrate the tuning and performance of the device by successfully measuring the spectra of methane and ammonia, verifying our approach's relevance for gas sensing. Our device signifies an important advance in nonlinear photonics miniaturization and brings practical field applications of high-speed and broadband mid-infrared spectroscopy closer to reality.Comment: 19 pages, 11 figure

Integrated Quantum Optical Phase Sensor

The quantum noise of light fundamentally limits optical phase sensors. A semiclassical picture attributes this noise to the random arrival time of photons from a coherent light source such as a laser. An engineered source of squeezed states suppresses this noise and allows sensitivity beyond the standard quantum limit (SQL) for phase detection. Advanced gravitational wave detectors like LIGO have already incorporated such sources, and nascent efforts in realizing quantum biological measurements have provided glimpses into new capabilities emerging in quantum measurement. We need ways to engineer and use quantum light within deployable quantum sensors that operate outside the confines of a lab environment. Here we present a photonic integrated circuit fabricated in thin-film lithium niobate that provides a path to meet these requirements. We use the second-order nonlinearity to produce a squeezed state at the same frequency as the pump light and realize circuit control and sensing with electro-optics. Using a 26.2 milliwatts of optical power, we measure (2.7 $\pm$ 0.2 )$\%$ squeezing and apply it to increase the signal-to-noise ratio of phase measurement. We anticipate that on-chip photonic systems like this, which operate with low power and integrate all of the needed functionality on a single die, will open new opportunities for quantum optical sensing.Comment: 14 pages, 3+3 figure

Integrated frequency-modulated optical parametric oscillator

Optical frequency combs have revolutionized precision measurement, time-keeping, and molecular spectroscopy. A substantial effort has developed around "microcombs": integrating comb-generating technologies into compact, reliable photonic platforms. Current approaches for generating these microcombs involve either the electro-optic (EO) or Kerr mechanisms. Despite rapid progress, maintaining high efficiency and wide bandwidth remains challenging. Here, we introduce a new class of microcomb -- an integrated optical frequency comb generator that combines electro-optics and parametric amplification to yield a frequency-modulated optical parametric oscillator (FM-OPO). In stark contrast to EO and Kerr combs, the FM-OPO microcomb does not form pulses but maintains operational simplicity and highly efficient pump power utilization with an output resembling a frequency-modulated laser. We outline the working principles of FM-OPO and demonstrate them by fabricating the complete optical system in thin-film lithium niobate (LNOI). We measure pump to comb internal conversion efficiency exceeding 93% (34% out-coupled) over a nearly flat-top spectral distribution spanning approximately 1,000 modes (approximately 6 THz). Compared to an EO comb, the cavity dispersion rather than loss determines the FM-OPO bandwidth, enabling broadband combs with a smaller RF modulation power. The FM-OPO microcomb, with its robust operational dynamics, high efficiency, and large bandwidth, contributes a new approach to the field of microcombs and promises to herald an era of miniaturized precision measurement, and spectroscopy tools to accelerate advancements in metrology, spectroscopy, telecommunications, sensing, and computing.Comment: 8 pages, 4 figures main text; another 19 pages and 9 figures in methods and supplementar

Single-Mode Squeezed Light Generation and Tomography with an Integrated Optical Parametric Oscillator

Quantum optical technologies promise advances in sensing, computing, and communication. A key resource is squeezed light, where quantum noise is redistributed between optical quadratures. We introduce a monolithic, chip-scale platform that exploits the $\chi^{(2)}$ nonlinearity of a thin-film lithium niobate (TFLN) resonator device to efficiently generate squeezed states of light. Our system integrates all essential components -- except for the laser and two detectors -- on a single chip with an area of one square centimeter, significantly reducing the size, operational complexity, and power consumption associated with conventional setups. Our work addresses challenges that have limited previous integrated nonlinear photonic implementations that rely on either $\chi^{(3)}$ nonlinear resonators or on integrated waveguide $\chi^{(2)}$ parametric amplifiers. Using the balanced homodyne measurement subsystem that we implemented on the same chip, we measure a squeezing of 0.55 dB and an anti-squeezing of 1.55 dB. We use 20 mW of input power to generate the parametric oscillator pump field by employing second harmonic generation on the same chip. Our work represents a substantial step toward compact and efficient quantum optical systems posed to leverage the rapid advances in integrated nonlinear and quantum photonics.Comment: 21 pages; 4 figures in main body, 8 supplementary figure

Efficient Photonic Integration of Diamond Color Centers and Thin-Film Lithium Niobate

On-chip photonic quantum circuits with integrated quantum memories have the potential to radically progress hardware for quantum information processing. In particular, negatively charged group-IV color centers in diamond are promising candidates for quantum memories, as they combine long storage times with excellent optical emission properties and an optically-addressable spin state. However, as a material, diamond lacks many functionalities needed to realize scalable quantum systems. Thin-film lithium niobate (TFLN), in contrast, offers a number of useful photonic nonlinearities, including the electro-optic effect, piezoelectricity, and capabilities for periodically-poled quasi-phase matching. Here, we present highly efficient heterogeneous integration of diamond nanobeams containing negatively charged silicon-vacancy (SiV) centers with TFLN waveguides. We observe greater than 90\% transmission efficiency between the diamond nanobeam and TFLN waveguide on average across multiple measurements. By comparing saturation signal levels between confocal and integrated collection, we determine a $10$-fold increase in photon counts channeled into TFLN waveguides versus that into out-of-plane collection channels. Our results constitute a key step for creating scalable integrated quantum photonic circuits that leverage the advantages of both diamond and TFLN materials

p21-Activated Kinases Are Required for Transformation in a Cell-Based Model of Neurofibromatosis Type 2

NF2 is an autosomal dominant disease characterized by development of bilateral vestibular schwannomas and other benign tumors in central nervous system. Loss of the NF2 gene product, Merlin, leads to aberrant Schwann cell proliferation, motility, and survival, but the mechanisms by which this tumor suppressor functions remain unclear. One well-defined target of Merlin is the group I family of p21-activated kinases, which are allosterically inhibited by Merlin and which, when activated, stimulate cell cycle progression, motility, and increased survival. Here, we examine the effect of Pak inhibition on cells with diminished Merlin function.Using a specific peptide inhibitor of group I Paks, we show that loss of Pak activity restores normal cell movement in cells lacking Merlin function. In addition, xenografts of such cells form fewer and smaller tumors than do cells without Pak inhibition. However, in tumors, loss of Pak activity does not reduce Erk or Akt activity, two signaling proteins that are thought to mediate Pak function in growth factor pathways.These results suggest that Pak functions in novel signaling pathways in NF2, and may serve as a useful therapeutic target in this disease

Evidence for Positive Selection on a Number of MicroRNA Regulatory Interactions during Recent Human Evolution

MicroRNA (miRNA)–mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

10.1371/journal.pone.0053830PLoS ONE81