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

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

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen.

BACKGROUND: The influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain. OBJECTIVE: We sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance. METHODS: We performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age. RESULTS: One thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age). CONCLUSION: Early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies

Social media abuse, online harassment and social work (Ireland edition)

The @UCCsocialwork Online Social Work Practice (OSWP) series supports social workers, professionals, community organisations, and practice managers providing services through online platforms

Chip-based laser with 1-hertz integrated linewidth

Lasers with hertz linewidths at time scales of seconds are critical for metrology, timekeeping, and manipulation of quantum systems. Such frequency stability relies on bulk-optic lasers and reference cavities, where increased size is leveraged to reduce noise but with the trade-off of cost, hand assembly, and limited applications. Alternatively, planar waveguide-based lasers enjoy complementary metal-oxide semiconductor scalability yet are fundamentally limited from achieving hertz linewidths by stochastic noise and thermal sensitivity. In this work, we demonstrate a laser system with a 1-s linewidth of 1.1 Hz and fractional frequency instability below 10-14 to 1 s. This low-noise performance leverages integrated lasers together with an 8-ml vacuum-gap cavity using microfabricated mirrors. All critical components are lithographically defined on planar substrates, holding potential for high-volume manufacturing. Consequently, this work provides an important advance toward compact lasers with hertz linewidths for portable optical clocks, radio frequency photonic oscillators, and related communication and navigation systems

Modeling and mitigation of high-concentration antibody viscosity through structure-based computer-aided protein design.

For an antibody to be a successful therapeutic many competing factors require optimization, including binding affinity, biophysical characteristics, and immunogenicity risk. Additional constraints may arise from the need to formulate antibodies at high concentrations (>150 mg/ml) to enable subcutaneous dosing with reasonable volume (ideally <1.0 mL). Unfortunately, antibodies at high concentrations may exhibit high viscosities that place impractical constraints (such as multiple injections or large needle diameters) on delivery and impede efficient manufacturing. Here we describe the optimization of an anti-PDGF-BB antibody to reduce viscosity, enabling an increase in the formulated concentration from 80 mg/ml to greater than 160 mg/ml, while maintaining the binding affinity. We performed two rounds of structure guided rational design to optimize the surface electrostatic properties. Analysis of this set demonstrated that a net-positive charge change, and disruption of negative charge patches were associated with decreased viscosity, but the effect was greatly dependent on the local surface environment. Our work here provides a comprehensive study exploring a wide sampling of charge-changes in the Fv and CDR regions along with targeting multiple negative charge patches. In total, we generated viscosity measurements for 40 unique antibody variants with full sequence information which provides a significantly larger and more complete dataset than has previously been reported

Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation

Summary: Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose. GDF15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. Similarly, in GDF15 knockout mice, the LPS effect on appetite and survival was comparable with that observed in wild-type controls. Therefore, effective inhibition of circulating active GDF15 via an antibody or via gene knockout demonstrated that survival in the LPS acute inflammation model was independent of GDF15