Self-emergence of robust solitons in a microcavity.

In many disciplines, states that emerge in open systems far from equilibrium are determined by a few global parameters1,2. These states can often mimic thermodynamic equilibrium, a classic example being the oscillation threshold of a laser3 that resembles a phase transition in condensed matter. However, many classes of states cannot form spontaneously in dissipative systems, and this is the case for cavity solitons2 that generally need to be induced by external perturbations, as in the case of optical memories4,5. In the past decade, these highly localized states have enabled important advancements in microresonator-based optical frequency combs6,7. However, the very advantages that make cavity solitons attractive for memories-their inability to form spontaneously from noise-have created fundamental challenges. As sources, microcombs require spontaneous and reliable initiation into a desired state that is intrinsically robust8-20. Here we show that the slow non-linearities of a free-running microresonator-filtered fibre laser21 can transform temporal cavity solitons into the system's dominant attractor. This phenomenon leads to reliable self-starting oscillation of microcavity solitons that are naturally robust to perturbations, recovering spontaneously even after complete disruption. These emerge repeatably and controllably into a large region of the global system parameter space in which specific states, highly stable over long timeframes, can be achieved.

11 TOPS photonic convolutional accelerator for optical neural networks.

Convolutional neural networks, inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to provide greatly reduced parametric complexity and to enhance the accuracy of prediction. They are of great interest for machine learning tasks such as computer vision, speech recognition, playing board games and medical diagnosis1-7. Optical neural networks offer the promise of dramatically accelerating computing speed using the broad optical bandwidths available. Here we demonstrate a universal optical vector convolutional accelerator operating at more than ten TOPS (trillions (1012) of operations per second, or tera-ops per second), generating convolutions of images with 250,000 pixels-sufficiently large for facial image recognition. We use the same hardware to sequentially form an optical convolutional neural network with ten output neurons, achieving successful recognition of handwritten digit images at 88 per cent accuracy. Our results are based on simultaneously interleaving temporal, wavelength and spatial dimensions enabled by an integrated microcomb source. This approach is scalable and trainable to much more complex networks for demanding applications such as autonomous vehicles and real-time video recognition.

Parametric interaction of laser cavity-solitons with an external CW pump.

We study the interaction of a laser cavity-soliton microcomb with an externally coupled, co-propagating tunable CW pump, observing parametric Kerr interactions which lead to the formation of both a cross-phase modulation and a four-wave mixing replica of the laser cavity-soliton. We compare and explain the dependence of the microcomb spectra from both the cavity-soliton and pump parameters, demonstrating the ability to adjust the microcomb externally without breaking or interfering with the soliton state. The parametric nature of the process agrees with numerical simulations. The parametric extended state maintains the typical robustness of laser-cavity solitons.

Dual-polarization RF channelizer based on microcombs.

We report a dual-polarization radio frequency (RF) channelizer based on microcombs. Two high-Q micro-ring resonators (MRRs) with slightly different free spectral ranges (FSRs) are used: one MRR is pumped to yield soliton crystal microcombs ("active"), and the other MRR is used as a "passive" periodic optical filter supporting dual-polarization operation to slice the RF spectrum. With the tailored mismatch between the FSRs of the active and passive MRRs, wideband RF spectra can be channelized into multiple segments featuring digital-compatible bandwidths via the Vernier effect. Due to the use of dual-polarization states, the number of channelized spectral segments, and thus the RF instantaneous bandwidth (with a certain spectral resolution), can be doubled. In our experiments, we used 20 microcomb lines with ∼ 49 GHz FSR to achieve 20 channels for each polarization, with high RF spectra slicing resolutions at 144 MHz (TE) and 163 MHz (TM), respectively; achieving an instantaneous RF operation bandwidth of 3.1 GHz (TE) and 2.2 GHz (TM). Our approach paves the path towards monolithically integrated photonic RF receivers (the key components - active and passive MRRs are all fabricated on the same platform) with reduced complexity, size, and unprecedented performance, which is important for wide RF applications with digital-compatible signal detection.

Evaluating In-home Assistive Technology for Dementia Caregivers.

OBJECTIVES: Dementia caregivers (CGs) are at heightened risk for developing problems with anxiety and depression. Much attention has been directed toward developing and deploying interventions designed to protect CG health, but few have been supported by rigorous empirical evidence. Technology-based interventions that are effective, scalable, and do not add greatly to the CG burden are of particular interest. METHODS: We conducted a nine-month randomized controlled trial in 63 homes evaluating People Power Caregiver (PPCg), a system of sensors in the home connected to cloud-based software that alerts CGs about worrisome deviations from normal patterns (e.g., falls, wandering). RESULTS: CGs in the active condition had significantly less anxiety than those in the control condition at the six-month assessment. Greater anxiety reduction in the active condition at the six-month assessment was associated with greater interaction with PPCg via SMS text messages. There were no differences in anxiety at the three-month or nine-month assessments or in depression at any assessment. CONCLUSIONS: PPCg shows promise for reducing anxiety associated with caring for a =person with dementia. CLINICAL IMPLICATIONS: Technology-based interventions can help reduce CG anxiety, a major adverse consequence of caregiving that may be difficult to treat due to other demands on caregiver time and energy.

Investigating the thermal robustness of soliton crystal microcombs.

Soliton crystals are a novel form of microcomb, with relatively high conversion efficiency, good thermal robustness, and simple initiation among the methods to generate them. Soliton crystals can be easily generated in microring resonators with an appropriate mode-crossing. However, fabrication defects can significantly affect the mode-crossing placement and strength in devices. To enable soliton crystal states to be harnessed for a broader range of microcomb applications, we need a better understanding of the link between mode-crossing properties and the desired soliton crystal properties. Here, we investigate how to generate the same soliton crystal state in two different microrings, how changes in microring temperature change the mode-crossing properties, and how mode-crossing properties affect the generation of our desired soliton crystal state. We find that temperature affects the mode-crossing position in these rings but without major changes in the mode-crossing strength. We find that our wanted state can be generated over a device temperature range of 25 ∘C, with different mode-crossing properties, and is insensitive to the precise mode-crossing position between resonances.

On-chip generation of high-dimensional entangled quantum states and their coherent control.

Optical quantum states based on entangled photons are essential for solving questions in fundamental physics and are at the heart of quantum information science. Specifically, the realization of high-dimensional states (D-level quantum systems, that is, qudits, with D > 2) and their control are necessary for fundamental investigations of quantum mechanics, for increasing the sensitivity of quantum imaging schemes, for improving the robustness and key rate of quantum communication protocols, for enabling a richer variety of quantum simulations, and for achieving more efficient and error-tolerant quantum computation. Integrated photonics has recently become a leading platform for the compact, cost-efficient, and stable generation and processing of non-classical optical states. However, so far, integrated entangled quantum sources have been limited to qubits (D = 2). Here we demonstrate on-chip generation of entangled qudit states, where the photons are created in a coherent superposition of multiple high-purity frequency modes. In particular, we confirm the realization of a quantum system with at least one hundred dimensions, formed by two entangled qudits with D = 10. Furthermore, using state-of-the-art, yet off-the-shelf telecommunications components, we introduce a coherent manipulation platform with which to control frequency-entangled states, capable of performing deterministic high-dimensional gate operations. We validate this platform by measuring Bell inequality violations and performing quantum state tomography. Our work enables the generation and processing of high-dimensional quantum states in a single spatial mode.

Thermo-Optic Response and Optical Bistablility of Integrated High-Index Doped Silica Ring Resonators.

The engineering of thermo-optic effects has found broad applications in integrated photonic devices, facilitating efficient light manipulation to achieve various functionalities. Here, we perform both an experimental characterization and a theoretical analysis of these effects in integrated microring resonators made from high-index doped silica, which have had many applications in integrated photonics and nonlinear optics. By fitting the experimental results with theory, we obtain fundamental parameters that characterize their thermo-optic performance, including the thermo-optic coefficient, the efficiency of the optically induced thermo-optic process, and the thermal conductivity. The characteristics of these parameters are compared to those of other materials commonly used for integrated photonic platforms, such as silicon, silicon nitride, and silica. These results offer a comprehensive insight into the thermo-optic properties of doped silica-based devices. Understanding these properties is essential for efficiently controlling and engineering them in many practical applications.

The impact of shoulder pathology on individuals with distal radius fracture.

BACKGROUND: Shoulder pathology can occur concurrently with a distal radius fracture (DRF) but few studies have examined this population. PURPOSE: The purpose of this study was to expand the understanding of the impact of shoulder pathology on individuals with DRF. STUDY DESIGN: Mixed Methods Design. METHODS: A total of 45 participants with a DRF were categorized into a DRF only (n = 29) and shoulder pathology concurrent with DRF (SPCDRF) (n = 16) groups. Quantitative data gathered included demographics, Quick Disabilities of the Arm, Shoulder, and Hand, Tampa Scale of Kinesiophobia-11, Visual Analog Scale, and Compensatory Mechanism Checklist. Qualitative interviews were performed with 7 participants in the SPCDRF group. Within group correlations were analyzed via the Spearman Rank. The Mann Whitney U test was used to compare the two groups. Qualitative analysis was performed to describe the experience of participants in the SPCDRF group. A mixed methods analysis compared quantitative and qualitative data. RESULTS: Sixteen participants (35.6%) in the sample presented with shoulder pathology; 6 participants (37.5%) presented at initial evaluation due to the fall; 10 participants (62.5%) developed shoulder pathology due to compensation or disuse. Average number of days to develop shoulder pathology after the DRF was 43 days. SPCDRF participants had significantly greater pain levels (p = .02) and more activity avoidance (p = .03) than the DRF only group. Four qualitative themes emerged: It's difficult to perform occupations and changes had to be made; There is fear and uncertainty; The impact of pain; Tried to be normal but could not Mixed methods analysis found that qualitative data further illuminated quantitative findings. CONCLUSIONS: Individuals with shoulder pathology concurrent with a DRF may present with higher pain levels and avoid activity more. In addition, they may describe fearfulness in using their injured upper extremity especially if they have high levels of pain. STUDY DESIGN: Mixed Methods Design.

flexiMAP: a regression-based method for discovering differential alternative polyadenylation events in standard RNA-seq data.

MOTIVATION: We present flexible Modeling of Alternative PolyAdenylation (flexiMAP), a new beta-regression-based method implemented in R, for discovering differential alternative polyadenylation events in standard RNA-seq data. RESULTS: We show, using both simulated and real data, that flexiMAP exhibits a good balance between specificity and sensitivity and compares favourably to existing methods, especially at low fold changes. In addition, the tests on simulated data reveal some hitherto unrecognized caveats of existing methods. Importantly, flexiMAP allows modeling of multiple known covariates that often confound the results of RNA-seq data analysis. AVAILABILITY AND IMPLEMENTATION: The flexiMAP R package is available at: https://github.com/kszkop/flexiMAP. Scripts and data to reproduce the analysis in this paper are available at: https://doi.org/10.5281/zenodo.3689788. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

High parametric efficiency in laser cavity-soliton microcombs.

Laser cavity-soliton microcombs are robust optical pulsed sources, usually implemented with a microresonator-filtered fibre laser. In such a configuration, a nonlinear microcavity converts the narrowband pulse resulting from bandwidth-limited amplification to a background-free broadband microcomb. Here, we theoretically and experimentally study the soliton conversion efficiency between the narrowband input pulse and the two outputs of a four-port integrated microcavity, namely the 'Drop' and 'Through' ports. We simultaneously measure on-chip, single-soliton conversion efficiencies of 45% and 25% for the two broadband comb outputs at the 'Drop' and 'Through' ports of a 48.9 GHz free-spectral range micro-ring resonator, obtaining a total conversion efficiency of 72%.

All-optical RF spectrum analyzer with a 5 THz bandwidth based on CMOS-compatible high-index doped silica waveguides.

We report an all-optical radio-frequency (RF) spectrum analyzer with a bandwidth greater than 5 THz, based on a 50 cm long spiral waveguide in a CMOS-compatible high-index doped silica platform. By carefully mapping out the dispersion profile of the waveguides for different thicknesses, we identify the optimal design to achieve near-zero dispersion in the C-band. To demonstrate the capability of the RF spectrum analyzer, we measure the optical output of a femtosecond fiber laser with an ultrafast optical RF spectrum in the terahertz regime.

Flexibility and intrinsic disorder are conserved features of hepatitis C virus E2 glycoprotein.

The glycoproteins of hepatitis C virus, E1E2, are unlike any other viral fusion machinery yet described, and are the current focus of immunogen design in HCV vaccine development; thus, making E1E2 both scientifically and medically important. We used pre-existing, but fragmentary, structures to model a complete ectodomain of the major glycoprotein E2 from three strains of HCV. We then performed molecular dynamic simulations to explore the conformational landscape of E2, revealing a number of important features. Despite high sequence divergence, and subtle differences in the models, E2 from different strains behave similarly, possessing a stable core flanked by highly flexible regions, some of which perform essential functions such as receptor binding. Comparison with sequence data suggest that this consistent behaviour is conferred by a network of conserved residues that act as hinge and anchor points throughout E2. The variable regions (HVR-1, HVR-2 and VR-3) exhibit particularly high flexibility, and bioinformatic analysis suggests that HVR-1 is a putative intrinsically disordered protein region. Dynamic cross-correlation analyses demonstrate intramolecular communication and suggest that specific regions, such as HVR-1, can exert influence throughout E2. To support our computational approach we performed small-angle X-ray scattering with purified E2 ectodomain; this data was consistent with our MD experiments, suggesting a compact globular core with peripheral flexible regions. This work captures the dynamic behaviour of E2 and has direct relevance to the interaction of HCV with cell-surface receptors and neutralising antibodies.

Plasmonic Resonant Nanoantennas Induce Changes in the Shape and the Intensity of Infrared Spectra of Phospholipids.

Surface enhanced infrared absorption spectroscopic studies (SEIRAS) as a technique to study biological molecules in extremely low concentrations is greatly evolving. In order to use the technique for identification of the structure and interactions of such biological molecules, it is necessary to identify the effects of the plasmonic electric-field enhancement on the spectral signature. In this study the spectral properties of 1,2-Dipalmitoyl-sn-glycero-3 phosphothioethanol (DPPTE) phospholipid immobilized on gold nanoantennas, specifically designed to enhance the vibrational fingerprints of lipid molecules were studied. An AFM study demonstrates an organization of the DPPTE phospholipid in bilayers on the nanoantenna structure. The spectral data were compared to SEIRAS active gold surfaces based on nanoparticles, plain gold and plain substrate (Si) for different temperatures. The shape of the infrared signals, the peak positions and their relative intensities were found to be sensitive to the type of surface and the presence of an enhancement. The strongest shifts in position and intensity were seen for the nanoantennas, and a smaller effect was seen for the DPPTE immobilized on gold nanoparticles. This information is crucial for interpretation of data obtained for biological molecules measured on such structures, for future application in nanodevices for biologically or medically relevant samples.

2D Layered Graphene Oxide Films Integrated with Micro-Ring Resonators for Enhanced Nonlinear Optics.

Layered 2D graphene oxide (GO) films are integrated with micro-ring resonators (MRRs) to experimentally demonstrate enhanced nonlinear optics. Both uniformly coated (1-5 layers) and patterned (10-50 layers) GO films are integrated on complementary-metal-oxide-semiconductor (CMOS)-compatible doped silica MRRs using a large-area, transfer-free, layer-by-layer GO coating method with precise control of the film thickness. The patterned devices further employ photolithography and lift-off processes to enable precise control of the film placement and coating length. Four-wave-mixing (FWM) measurements for different pump powers and resonant wavelengths show a significant improvement in efficiency of ≈7.6 dB for a uniformly coated device with 1 GO layer and ≈10.3 dB for a patterned device with 50 GO layers. The measurements agree well with theory, with the enhancement in FWM efficiency resulting from the high Kerr nonlinearity and low loss of the GO films combined with the strong light-matter interaction within the MRRs. The dependence of GO's third-order nonlinearity on layer number and pump power is also extracted from the FWM measurements, revealing interesting physical insights about the evolution of the GO films from 2D monolayers to quasi bulk-like behavior. These results confirm the high nonlinear optical performance of integrated photonic resonators incorporated with 2D layered GO films.

Mid-infrared supercontinuum generation in silicon-germanium all-normal dispersion waveguides.

We demonstrate coherent supercontinuum generation spanning over an octave from a silicon germanium-on-silicon waveguide using ∼200fs pulses at a wavelength of 4 µm. The waveguide is engineered to provide low all-normal dispersion in the TM polarization. We validate the coherence of the generated supercontinuum via simulations, with a high degree of coherence across the entire spectrum. Such a generated supercontinuum could lend itself to pulse compression down to 22 fs.

ABO Blood Group and Transfusions In the Intraoperative and Postoperative Period After LVAD Implantation.

OBJECTIVES: To assess whether blood group O patients undergoing left ventricular assist device (LVAD) insertion have higher perioperative transfusion requirements, postoperative chest tube output, and postoperative changes in hematocrit. DESIGN: Retrospective review of 116 LVAD patients from August 2015 to May 2018. SETTING: Single-institution, urban academic medical center. PARTICIPANTS: One hundred sixteen LVAD patients analyzed by blood group: group O (n = 49) versus non-O (n = 67). INTERVENTIONS: Transfusions in the combined intraoperative and postoperative period at 7 days and 90 days after LVAD implantation, chest tube output in the first 24 hours, and hematocrit change in the first 48 hours postoperatively. RESULTS: There was no difference between group O and non-O within the univariable analysis for both 7-day and 90-day transfusion rates. Adjusting for covariables, blood type O was not associated with packed red blood cells transfusion after accounting for multiple comparisons (odds ratio 1.33 [1.07-1.66], p = 0.01, where p < 0.005 was considered statistically significant as a Bonferroni correction was performed to control the familywise error rate). Additionally, there was no difference in chest tube output over the first 24 hours (1,129 v 1,057 mL, p = 0.47) or hematocrit change in the first 48 hours postoperatively (3.49 v 4.53%, p = 0.15). CONCLUSION: O blood group is not a significant predictor of transfusion requirements in the combined intraoperative and postoperative period up to 90 days after LVAD implantation.

Highly reconfigurable hybrid laser based on an integrated nonlinear waveguide.

The ability of laser systems to emit different adjustable temporal pulse profiles and patterns is desirable for a broad range of applications. While passive mode-locking techniques have been widely employed for the realization of ultrafast laser pulses with mainly Gaussian or hyperbolic secant temporal profiles, the generation of versatile pulse shapes in a controllable way and from a single laser system remains a challenge. Here we show that a nonlinear amplifying loop mirror (NALM) laser with a bandwidth-limiting filter (in a nearly dispersion-free arrangement) and a short integrated nonlinear waveguide enables the realization and distinct control of multiple mode-locked pulsing regimes (e.g., Gaussian pulses, square waves, fast sinusoidal-like oscillations) with repetition rates that are variable from the fundamental (7.63 MHz) through its 205th harmonic (1.56 GHz). These dynamics are described by a newly developed and compact theoretical model, which well agrees with our experimental results. It attributes the control of emission regimes to the change of the NALM response function that is achieved by the adjustable interplay between the NALM amplification and the nonlinearity. In contrast to previous square wave emissions, we experimentally observed that an Ikeda instability was responsible for square wave generation. The presented approach enables laser systems that can be universally applied to various applications, e.g., spectroscopy, ultrafast signal processing and generation of non-classical light states.

Factor VIII cross-matches to the human proteome reduce the predicted inhibitor risk in missense mutation hemophilia A.

Single missense mutations in the F8 gene encoding the coagulation protein factor VIII give rise predominantly to non-severe hemophilia A. Despite only a single amino acid sequence difference between the replacement, therapeutic factor VIII and the patient's endogenous factor VIII, therapeutic factor VIII may still be perceived as foreign by the recipient's immune system and trigger an immune response (inhibitor). Inhibitor formation is a life-long risk for patients with non-severe hemophilia A treated with therapeutic factor VIII, but remains difficult to predict. The aim of this study was to understand whether fortuitous, primary sequence cross-matches between therapeutic factor VIII and proteins in the human proteome are the reason why certain F8 mutations are not associated with inhibitor formation. We predicted which therapeutic factor VIII differences are potentially perceived as foreign by helper T cells - a necessary precursor to inhibitor development - and then scanned potentially immunogenic peptides against more than 100,000 proteins in the proteome. As there are hundreds of disease-causing F8 missense mutations and the human leukocyte antigen gene complex governing peptide presentation to helper T cells is highly polymorphic, these calculations pose a huge combinatorial challenge that we addressed computationally. We found that cross-matches between therapeutic factor VIII and the human proteome are commonplace and have a profound impact on the predicted risk of inhibitor development. Our results emphasize the importance of knowing both the F8 missense mutation and the human leukocyte antigen alleles of a patient with missense mutation hemophilia A if his underlying risk of inhibitor development is to be estimated.