Ultralow phase noise microwave generation with an Er:fiber-based optical frequency divider

We present an optical frequency divider based on a 200 MHz repetition rate Er:fiber mode-locked laser that, when locked to a stable optical frequency reference, generates microwave signals with absolute phase noise that is equal to or better than cryogenic microwave oscillators. At 1 Hz offset from a 10 GHz carrier, the phase noise is below -100 dBc/Hz, limited by the optical reference. For offset frequencies > 10 kHz, the phase noise is shot noise limited at -145 dBc/Hz. An analysis of the contribution of the residual noise from the Er:fiber optical frequency divider is also presented.Comment: 4 pages, 3 figure

Electronic initiation and optimization of nonlinear polarization evolution mode-locking in a fiber laser

We describe a system for automated modelocking and optimization of a fiber laser oscillator employing nonlinear polarization evolution. Using four liquid crystal variable retarders, we fully control the fiber launch and output polarization states, enabling compensation for mechanical and environmental perturbations to the fiber cavity. We demonstrate mapping of the modelocking regions for an ANDi fiber oscillator and demonstrate that local and global optimization algorithms can be used to maintain the laser in the same operating state. This technique enables robust operation of nonlinear polarization evolution modelocked fiber lasers, rivaling the stability of PM fiber lasers while maintaining the advantages of the NPE modelocking mechanism

The association between implementation strategy use and the uptake of hepatitis C treatment in a national sample

Abstract Background Hepatitis C virus (HCV) is a common and highly morbid illness. New medications that have much higher cure rates have become the new evidence-based practice in the field. Understanding the implementation of these new medications nationally provides an opportunity to advance the understanding of the role of implementation strategies in clinical outcomes on a large scale. The Expert Recommendations for Implementing Change (ERIC) study defined discrete implementation strategies and clustered these strategies into groups. The present evaluation assessed the use of these strategies and clusters in the context of HCV treatment across the US Department of Veterans Affairs (VA), Veterans Health Administration, the largest provider of HCV care nationally. Methods A 73-item survey was developed and sent to all VA sites treating HCV via electronic survey, to assess whether or not a site used each ERIC-defined implementation strategy related to employing the new HCV medication in 2014. VA national data regarding the number of Veterans starting on the new HCV medications at each site were collected. The associations between treatment starts and number and type of implementation strategies were assessed. Results A total of 80 (62%) sites responded. Respondents endorsed an average of 25 ± 14 strategies. The number of treatment starts was positively correlated with the total number of strategies endorsed (r = 0.43, p < 0.001). Quartile of treatment starts was significantly associated with the number of strategies endorsed (p < 0.01), with the top quartile endorsing a median of 33 strategies, compared to 15 strategies in the lowest quartile. There were significant differences in the types of strategies endorsed by sites in the highest and lowest quartiles of treatment starts. Four of the 10 top strategies for sites in the top quartile had significant correlations with treatment starts compared to only 1 of the 10 top strategies in the bottom quartile sites. Overall, only 3 of the top 15 most frequently used strategies were associated with treatment. Conclusions These results suggest that sites that used a greater number of implementation strategies were able to deliver more evidence-based treatment in HCV. The current assessment also demonstrates the feasibility of electronic self-reporting to evaluate ERIC strategies on a large scale. These results provide initial evidence for the clinical relevance of the ERIC strategies in a real-world implementation setting on a large scale. This is an initial step in identifying which strategies are associated with the uptake of evidence-based practices in nationwide healthcare systems

Frequency-stabilization to 6x10^-16 via spectral-hole burning

We demonstrate two-stage laser stabilization based on a combination of Fabry- Perot and spectral-hole burning techniques. The laser is first pre-stabilized by the Fabry-Perot cavity to a fractional-frequency stability of sigma_y(tau) < 10^-13. A pattern of spectral holes written in the absorption spectrum of Eu3+:Y2SiO5 serves to further stabilize the laser to sigma_y(tau) = 6x10^-16 for 2 s < tau < 8 s. Measurements characterizing the frequency sensitivity of Eu3+:Y2SiO5 spectral holes to environmental perturbations suggest that they can be more frequency stable than Fabry-Perot cavities

Pseudomonas aeruginosa PilY1 Binds Integrin in an RGD- and Calcium-Dependent Manner

PilY1 is a type IV pilus (tfp)-associated protein from the opportunistic pathogen Pseudomonas aeruginosa that shares functional similarity with related proteins in infectious Neisseria and Kingella species. Previous data have shown that PilY1 acts as a calcium-dependent pilus biogenesis factor necessary for twitching motility with a specific calcium binding site located at amino acids 850–859 in the 1,163 residue protein. In addition to motility, PilY1 is also thought to play an important role in the adhesion of P. aeruginosa tfp to host epithelial cells. Here, we show that PilY1 contains an integrin binding arginine-glycine-aspartic acid (RGD) motif located at residues 619–621 in the PilY1 from the PAK strain of P. aeruginosa; this motif is conserved in the PilY1s from the other P. aeruginosa strains of known sequence. We demonstrate that purified PilY1 binds integrin in vitro in an RGD-dependent manner. Furthermore, we identify a second calcium binding site (amino acids 600–608) located ten residues upstream of the RGD. Eliminating calcium binding from this site using a D608A mutation abolished integrin binding; in contrast, a calcium binding mimic (D608K) preserved integrin binding. Finally, we show that the previously established PilY1 calcium binding site at 851–859 also impacts the protein's association with integrin. Taken together, these data indicate that PilY1 binds to integrin in an RGD- and calcium-dependent manner in vitro. As such, P. aeruginosa may employ these interactions to mediate host epithelial cell binding in vivo

Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease.

RATIONALE: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. OBJECTIVE: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. METHODS AND RESULTS: We sequenced the exons of the CETP gene in 58 469 participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; P<1.0×10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; P=5.1×10-3). CONCLUSIONS: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD

Machine learning uncovers the most robust self-report predictors of relationship quality across 43 longitudinal couples studies

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner’s ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person’s own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships

Association of Rare and Common Variation in the Lipoprotein Lipase Gene With Coronary Artery Disease.

IMPORTANCE: The activity of lipoprotein lipase (LPL) is the rate-determining step in clearing triglyceride-rich lipoproteins from the circulation. Mutations that damage the LPL gene (LPL) lead to lifelong deficiency in enzymatic activity and can provide insight into the relationship of LPL to human disease. OBJECTIVE: To determine whether rare and/or common variants in LPL are associated with early-onset coronary artery disease (CAD). DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional study, LPL was sequenced in 10 CAD case-control cohorts of the multinational Myocardial Infarction Genetics Consortium and a nested CAD case-control cohort of the Geisinger Health System DiscovEHR cohort between 2010 and 2015. Common variants were genotyped in up to 305 699 individuals of the Global Lipids Genetics Consortium and up to 120 600 individuals of the CARDIoGRAM Exome Consortium between 2012 and 2014. Study-specific estimates were pooled via meta-analysis. EXPOSURES: Rare damaging mutations in LPL included loss-of-function variants and missense variants annotated as pathogenic in a human genetics database or predicted to be damaging by computer prediction algorithms trained to identify mutations that impair protein function. Common variants in the LPL gene region included those independently associated with circulating triglyceride levels. MAIN OUTCOMES AND MEASURES: Circulating lipid levels and CAD. RESULTS: Among 46 891 individuals with LPL gene sequencing data available, the mean (SD) age was 50 (12.6) years and 51% were female. A total of 188 participants (0.40%; 95% CI, 0.35%-0.46%) carried a damaging mutation in LPL, including 105 of 32 646 control participants (0.32%) and 83 of 14 245 participants with early-onset CAD (0.58%). Compared with 46 703 noncarriers, the 188 heterozygous carriers of an LPL damaging mutation displayed higher plasma triglyceride levels (19.6 mg/dL; 95% CI, 4.6-34.6 mg/dL) and higher odds of CAD (odds ratio = 1.84; 95% CI, 1.35-2.51; P < .001). An analysis of 6 common LPL variants resulted in an odds ratio for CAD of 1.51 (95% CI, 1.39-1.64; P = 1.1 × 10-22) per 1-SD increase in triglycerides. CONCLUSIONS AND RELEVANCE: The presence of rare damaging mutations in LPL was significantly associated with higher triglyceride levels and presence of coronary artery disease. However, further research is needed to assess whether there are causal mechanisms by which heterozygous lipoprotein lipase deficiency could lead to coronary artery disease