Frequency combs induced by phase turbulence.

Wave instability-the process that gives rise to turbulence in hydrodynamics1-represents the mechanism by which a small disturbance in a wave grows in amplitude owing to nonlinear interactions. In photonics, wave instabilities result in modulated light waveforms that can become periodic in the presence of coherent locking mechanisms. These periodic optical waveforms are known as optical frequency combs2-4. In ring microresonator combs5,6, an injected monochromatic wave becomes destabilized by the interplay between the resonator dispersion and the Kerr nonlinearity of the constituent crystal. By contrast, in ring lasers instabilities are considered to occur only under extreme pumping conditions7,8. Here we show that, despite this notion, semiconductor ring lasers with ultrafast gain recovery9,10 can enter frequency comb regimes at low pumping levels owing to phase turbulence11-an instability known to occur in hydrodynamics, superconductors and Bose-Einstein condensates. This instability arises from the phase-amplitude coupling of the laser field provided by linewidth enhancement12, which produces the needed interplay of dispersive and nonlinear effects. We formulate the instability condition in the framework of the Ginzburg-Landau formalism11. The localized structures that we observe share several properties with dissipative Kerr solitons, providing a first step towards connecting semiconductor ring lasers and microresonator frequency combs13.

Optical properties of metasurfaces infiltrated with liquid crystals.

Optical metasurfaces allow the ability to precisely manipulate the wavefront of light, creating many interesting and exotic optical phenomena. However, they generally lack dynamic control over their optical properties and are limited to passive optical elements. In this work, we report the nontrivial infiltration of nanostructured metalenses with three respective nematic liquid crystals of different refractive index and birefringence. The optical properties of the metalens are evaluated after liquid-crystal infiltration to quantify its effect on the intended optical design. We observe a significant modification of the metalens focus after infiltration for each liquid crystal. These optical changes result from modification of local refractive index surrounding the metalens structure after infiltration. We report qualitative agreement of the optical experiments with finite-difference time-domain solver (FDTD) simulation results. By harnessing the tunability inherent in the orientation dependent refractive index of the infiltrated liquid crystal, the metalens system considered here has the potential to enable dynamic reconfigurability in metasurfaces.

Single stage biventricular repair of hypoplastic right ventricle with straddling tricuspid valve.

We present the case of a five-year-old child with an inlet ventricular septal defect, subpulmonic stenosis, hypoplastic right ventricle, and straddling tricuspid valve who received a successful one-stage biventricular repair with right ventricular rehabilitation, right ventricular outflow tract augmentation, papillary muscle transposition, ventricular septal defect closure, and fenestrated atrial septation. This report outlines the surgical decision making and operative technique.

T cell-inflamed gene expression profile and PD-L1 expression and pembrolizumab efficacy in advanced esophageal cancer.

Aim: Investigate the relationship between response to pembrolizumab and expression of the 18-gene T cell-inflamed gene expression profile (TcellinfGEP) or PD-L1 combined positive score (CPS) in esophageal cancer. Materials & methods: This analysis included heavily pretreated patients with advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma who received pembrolizumab in the single-arm, phase II study KEYNOTE-180. PD-L1 CPS was evaluated with PD-L1 IHC 22C3 pharmDx. Results: In patients with squamous cell carcinoma, trends toward enrichment for responders were observed for patients with PD-L1 CPS ≥10 tumors. In patients with adenocarcinoma, a trend was observed for TcellinfGEP but not for PD-L1. Conclusion: TcellinfGEP and PD-L1 CPS may enrich for responders to pembrolizumab in patients with esophageal cancer. Clinical trial registration: NCT02559687 (ClinicalTrials.gov).

First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811.

Treatment options for patients with HER2-positive advanced gastric cancer are limited, and the prognosis for these patients is poor. Pembrolizumab has demonstrated promising antitumor activity in patients with advanced gastric or gastroesophageal junction adenocarcinoma as monotherapy, in combination with chemotherapy and in combination with trastuzumab. Combining pembrolizumab with trastuzumab and chemotherapy may therefore provide a benefit for patients with advanced HER2-positive gastric cancer. Here we aimed to describe the design of and rationale for the randomized, double-blind, placebo-controlled Phase III KEYNOTE-811 study, which will evaluate the efficacy and safety of pembrolizumab or placebo in combination with trastuzumab and chemotherapy as first-line treatment for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. Clinical trial registration: NCT03615326 (ClinicalTrials.gov).

Broadband Achromatic Metasurface-Refractive Optics.

Existing methods of correcting for chromatic aberrations in optical systems are limited to two approaches: varying the material dispersion in refractive lenses or incorporating grating dispersion via diffractive optical elements. Recently, single-layer broadband achromatic metasurface lenses have been demonstrated but are limited to diameters on the order of 100 µm due to the large required group delays. Here, we circumvent this limitation and design a metacorrector by combining a tunable phase and artificial dispersion to correct spherical and chromatic aberrations in a large spherical plano-convex lens. The tunability results from a variation in light confinement in sub-wavelength waveguides by locally tailoring the effective refractive index. The effectiveness of this approach is further validated by designing a metacorrector, which greatly increases the bandwidth of a state-of-the-art immersion objective (composed of 14 lenses and 7 types of glasses) from violet to near-infrared wavelengths. This concept of hybrid metasurface-refractive optics combines the advantages of both technologies in terms of size, scalability, complexity, and functionality.

Single-Layer Metasurface with Controllable Multiwavelength Functions.

In this paper, we report dispersion-engineered metasurfaces with distinct functionalities controlled by wavelength. Unlike previous approaches based on spatial multiplexing or vertical stacking of metasurfaces, we utilize a single phase profile with wavelength dependence encoded in the phase shifters' dispersion. We designed and fabricated a multiwavelength achromatic metalens (MAM) with achromatic focusing for blue (B), green (G), yellow (Y), and red (R) light and two wavelength-controlled beam generators (WCBG): one focuses light with orbital angular momentum (OAM) states ( l = 0,1,2) corresponding to three primary colors; the other produces ordinary focal spots ( l = 0) for red and green light, while generating a vortex beam ( l = 1) in the blue. A full color (RGB) hologram is also demonstrated in simulation. Our approach opens a path to applications ranging from near-eye displays and holography to compact multiwavelength beam generation.

Optical coherence tomography guided carotid artery stent procedure: technique and potential applications.

OBJECTIVES: To (1) present a guide on how to perform optical coherence tomography (OCT) in carotid artery stenting (CAS), to (2) highlight several instructive cases illustrating OCT-guidance as an interventional strategy, and to (3) present the largest case-series of OCT-guided CAS performed in North America, demonstrating its feasibility as an imaging modality in this setting. BACKGROUND: OCT is an intravascular imaging method that captures images with an axial resolution 10 times higher than intravascular ultrasound. OCT has proven to be a useful modality in coronary angiography and may have similar applications in evaluating carotid atherosclerotic disease. METHODS: We compared our experience in CAS utilizing OCT (40 patients) versus that of CAS without OCT guidance (52 patients). RESULTS: No strokes or deaths occurred in either group postprocedurally or at 12 months. Fluoroscopy time was reduced in the OCT arm (14 ± 1 vs. 16 ± 1 min). Postprocedural creatinine levels were identical (1 ± 0 mg/dl, P = 0.96). Procedure time (96 ± 8 vs. 80 ± 3 min, P = 0.06) and contrast use (94 ± 4 vs. 83 ± 4 ml, P = 0.05) was slightly elevated in the OCT arm. CONCLUSIONS: We established a standardized protocol to consistently obtain OCT images that helped guide interventional decision-making during CAS. OCT imaging in the carotids requires a higher contrast load and prolongs procedure time. However, it can be performed without significant increases in fluoroscopy time or negatively affecting renal function. There were no negative safety signals in this pilot study.

Immersion Meta-Lenses at Visible Wavelengths for Nanoscale Imaging.

Immersion objectives can focus light into a spot smaller than what is achievable in free space, thereby enhancing the spatial resolution for various applications such as microscopy, spectroscopy, and lithography. Despite the availability of advanced lens polishing techniques, hand-polishing is still required to manufacture the front lens of a high-end immersion objective, which poses major constraints for lens design. This limits the shape of the front lens to spherical. Therefore, several other lenses need to be cascaded to correct for spherical aberration, resulting in significant challenges for miniaturization and adding design complexity for different immersion liquids. Here, by using metasurfaces, we demonstrate liquid immersion meta-lenses free of spherical aberration at various design wavelengths in the visible spectrum. We report water and oil immersion meta-lenses of various numerical apertures (NA) up to 1.1 and show that their measured focal spot sizes are diffraction-limited with Strehl ratios of approximately 0.9 at 532 nm. By integrating the oil immersion meta-lens (NA = 1.1) into a commercial scanning confocal microscope, we achieve an imaging spatial resolution of approximately 200 nm. These meta-lenses can be easily adapted to focus light through multilayers of different refractive indices and mass-produced using modern industrial manufacturing or nanoimprint techniques, leading to cost-effective high-end optics.

Spin-to-orbital angular momentum conversion in dielectric metasurfaces: erratum.

We would like to clarify our paper [Opt. Express25, 377 (2017)] abstract sentence "These beams carry orbital angular momentum proportional to the number of intertwined helices constituting the wavefront."

Spin-to-orbital angular momentum conversion in dielectric metasurfaces.

Vortex beams are characterized by a helical wavefront and a phase singularity point on the propagation axis that results in a doughnut-like intensity profile. These beams carry orbital angular momentum proportional to the number of intertwined helices constituting the wavefront. Vortex beams have many applications in optics, such as optical trapping, quantum optics and microscopy. Although beams with such characteristics can be generated holographically, spin-to-orbital angular momentum conversion has attracted considerable interest as a tool to create vortex beams. In this process, the geometrical phase is exploited to create helical beams whose handedness is determined by the circular polarization (left/right) of the incident light, that is by its spin. Here we demonstrate high-efficiency Spin-to-Orbital angular momentum-Converters (SOCs) at visible wavelengths based on dielectric metasurfaces. With these SOCs we generate vortex beams with high and fractional topological charge and show for the first time the simultaneous generation of collinear helical beams with different and arbitrary orbital angular momentum. This versatile method of creating vortex beams, which circumvents the limitations of liquid crystal SOCs and adds new functionalities, should significantly expand the applications of these beams.

Freestanding dielectric nanohole array metasurface for mid-infrared wavelength applications.

We designed and simulated freestanding dielectric optical metasurfaces based on arrays of etched nanoholes in a silicon membrane. We showed 2π phase control and high forward transmission at mid-infrared (mid-IR) wavelengths around 4.2 µm by tuning the dimensions of the holes. We also identified the mechanisms responsible for high forward scattering efficiency and showed that these conditions are connected with the well-known Kerker conditions already proposed for isolated scatterers. A beam deflector was designed and optimized through sequential particle swarm and gradient descent optimization to maximize transmission efficiency and reduce unwanted grating orders. Such freestanding silicon nanohole array metasurfaces are promising for the realization of silicon-based mid-IR optical elements.

Band structure and dispersion engineering of strongly coupled plasmon-phonon-polaritons in graphene-integrated structures.

We theoretically investigate the polaritonic band structure and dispersion properties of graphene using transfer matrix methods, with strongly coupled graphene plasmons (GPs) and molecular infrared vibrations as a representative example. Two common geometrical configurations are considered: graphene coupled subwavelength dielectric grating (GSWDG) and graphene nanoribbons (GNR). By exploiting the dispersion and the band structure, we show the possibility of tailoring desired polaritonic behavior in each of the two configurations. We compare the strength of coupling occurring in both structures and find that the interaction is stronger in GNR than that of GSWDG structure as a result of the stronger field confinement of the edge modes. The band structure and dispersion analysis not only sheds light on the physics of the hybridized polariton formation but also offers insight into tailoring the optical response of graphene light-matter interactions for numerous applications, such as biomolecular sensing and detection.

Piezoelectric tuning of narrowband perfect plasmonic absorbers via an optomechanic cavity.

Optical antennas enable the control of light-matter interaction on the nanometer scale. Efficient on-chip electrical switching of plasmonic resonances is a crucial step toward the integration of optical antennas into practical optoelectronic circuits. We propose and numerically investigate the on-chip low-voltage linear electrical tuning of a narrowband optical antenna perfect absorber via a piezoelectric optomechanic cavity. Near unity absorption is realized by an array of gold nanostrip antennas separated from a membrane-based deformable backreflector by a small gap. A narrow linewidth of 33 nm at 2.58 µm is realized through the coupling between the plasmonic mode and photonic mode in the cavity-enhanced antenna structure. An aluminum nitride piezoelectric layer enabled efficient actuation of the backreflector and therefore changed the gap size, allowing for the tuning of the spectral absorption. The peak wavelength can be shifted linearly by 250 nm with 10 V of tuning voltage, and the tuning range is not limited by the pull-in effect. The polarization dependence of the nanostrip antenna coupled with the optomechanic cavity allows the use of our device as a voltage tunable polarization control device.

Wavelength tunable microdisk cavity light source with a chemically enhanced MoS2 emitter.

In this work, we report an integrated narrowband light source based on thin MoS2 emissive material coupled to the high quality factor whispering gallery modes of a microdisk cavity with a spatial notch that enables easy out-coupling of emission while it yields high spatial coherence and a Gaussian intensity distribution. The active light emitting material consists of chemically enhanced bilayer MoS2 flakes with a thin atomic layer deposited SiO2 protective coating that yields 20-times brighter chemically enhanced photoluminescence compared to as-exfoliated monolayers on the microdisk. Quality factors ≈ 1000 are observed as well as a high degree of spatial coherence. We also experimentally achieve effective index tuning of cavity coupled emission over a full free spectral range. The thermal response of this system is also studied. This work provides new insights for nanophotonic light sources with atomically thin active media.

Postnatal xenogeneic B-cell tolerance in swine following in utero intraportal antigen exposure.

BACKGROUND: The objective of this study was to investigate the humoral immune response to xenogeneic antigens administered during the fetal state utilizing a baboon-to-pig model. METHODS: Nine fetuses from an alpha-1,3-galactosyltransferase gene knockout (GalT-KO) MGH-miniature swine sow underwent transuterine ultrasound-guided intraportal injection of T-cell depleted baboon bone marrow (B-BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct B-BM intraportal injection were used as controls. RESULTS: Postnatal humoral tolerance was induced in the long-term surviving piglets as demonstrated by the absence of any antibody response to baboon donor cells. In addition, a second intraportal B-BM administration at 2.5 months post-birth led to no antibody formation despite re-exposure to xenogeneic antigens. This B-cell unresponsiveness was abrogated only when the animal was exposed subcutaneously to third-party xenogeneic and allogeneic antigens, suggesting that the previously achieved humoral non-responsiveness was donor specific. In comparison, the two juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG levels following intraportal injection. CONCLUSIONS: In summary, xenogeneic B-cell tolerance was induced through in utero intraportal exposure to donor cells and this tolerance persisted following postnatal rechallenge with donor B-BM, but was lost on exposure to third-party antigen, possibly as a result of cross-reactive antibody formation.

Optoelectromechanical multimodal biosensor with graphene active region.

A general, overarching theme in nanotechnology is the integration of multiple disparate fields to realize novel or expanded functionalities. Here, we present a graphene enabled, integrated optoelectromechanical device and demonstrate its utility for biomolecular sensing. We experimentally achieve an ultrawide linear dynamic sensing range of 5 orders of magnitude of protein concentration, an improvement over state-of-the-art single mode nanosensors by approximately 2-3 orders of magnitude, while retaining a subpicomolar lowest detection limit. Moreover, the ability to monitor and characterize adsorption events in the full optoelectromechanical space allows for the extraction of key intrinsic parameters of adsorbates and has the potential to extend the capabilities of nanosensors beyond the traditional binary-valued test for a single type of molecule. This could have significant implications for molecular detection applications at variable concentrations, such as early disease detection in biomedical diagnostics.

Guided mode resonance enabled ultra-compact Germanium photodetector for 1.55 µm detection.

We propose a novel technique of enhancing the photodetection capabilities of ultrathin Ge films for normally incident light at 1.55 µm through the guided mode resonance (GMR) phenomenon. Specifically, by suitably patterning the surface of a Ge thin film, it is possible to excite guided modes which are subsequently coupled to free space radiative modes, resulting in spectral resonances that possess locally enhanced near fields with a large spatial extent. Absorption is found to be enhanced by over an order of magnitude over a pristine Ge film of equal thickness. Furthermore, attenuation of incident light for such a structure occurs over very few grating periods, resulting in significantly enhanced theoretical 3 dB bandwidth-efficiency products of ~58 GHz. The nature of the enhancement mechanism also produces spectrally narrow resonances (FWHM ~30 nm) that are polarization sensitive and exhibit excellent angular tolerance. Finally, the proposed device architecture is fully compatible with existing Si infrastructure and current CMOS fabrication processes.

Increased transfusion-free survival following auxiliary pig liver xenotransplantation.

BACKGROUND: Pig to baboon liver xenotransplantation typically results in severe thrombocytopenia and coagulation disturbances, culminating in death from hemorrhage within 9 days, in spite of continuous transfusions. We studied the contribution of anticoagulant production and clotting pathway deficiencies to fatal bleeding in baboon recipients of porcine livers. METHODS: By transplanting liver xenografts from α1,3-galactosyltransferase gene-knockout (GalT-KO) miniature swine donors into baboons as auxiliary organs, leaving the native liver in place, we provided the full spectrum of primate clotting factors and allowed in vivo mixing of porcine and primate coagulation systems. RESULTS: Recipients of auxiliary liver xenografts develop severe thrombocytopenia, comparable to recipients of conventional orthotopic liver xenografts and consistent with hepatic xenograft sequestration. However, baboons with both pig and native livers do not exhibit clinical signs of bleeding and maintain stable blood counts without transfusion for up to 8 consecutive days post-transplantation. Instead, recipients of auxiliary liver xenografts undergo graft failure or die of sepsis, associated with thrombotic microangiopathy in the xenograft, but not the native liver. CONCLUSION: Our data indicate that massive hemorrhage in the setting of liver xenotransplantation might be avoided by supplementation with primate clotting components. However, coagulation competent hepatic xenograft recipients may be predisposed to graft loss related to small vessel thrombosis and ischemic necrosis.

scATAnno: Automated Cell Type Annotation for single-cell ATAC Sequencing Data.

Recent advances in single-cell epigenomic techniques have created a growing demand for scATAC-seq analysis. One key analysis task is to determine cell type identity based on the epigenetic data. We introduce scATAnno, a python package designed to automatically annotate scATAC-seq data using large-scale scATAC-seq reference atlases. This workflow generates the reference atlases from publicly available datasets enabling accurate cell type annotation by integrating query data with reference atlases, without the use of scRNA-seq data. To enhance annotation accuracy, we have incorporated KNN-based and weighted distance-based uncertainty scores to effectively detect cell populations within the query data that are distinct from all cell types in the reference data. We compare and benchmark scATAnno against 7 other published approaches for cell annotation and show superior performance in multiple data sets and metrics. We showcase the utility of scATAnno across multiple datasets, including peripheral blood mononuclear cell (PBMC), Triple Negative Breast Cancer (TNBC), and basal cell carcinoma (BCC), and demonstrate that scATAnno accurately annotates cell types across conditions. Overall, scATAnno is a useful tool for scATAC-seq reference building and cell type annotation in scATAC-seq data and can aid in the interpretation of new scATAC-seq datasets in complex biological systems.