Nonlinear Quantum Behavior of Ultrashort-Pulse Optical Parametric Oscillators

The quantum features of ultrashort-pulse optical parametric oscillators (OPOs) are theoretically investigated in the nonlinear regime near and above threshold. Starting from basic premises of input-output theory, we derive a general quantum model for pulsed OPOs subject to χ(2) interactions between a multimode signal cavity and a non-resonant broadband pump field, elucidating time scale conditions required for such pulsed OPOs to admit an input-output description. By employing a supermode decomposition of the nonlinear Lindblad operators governing pump-signal interactions, we perform multimode quantum simulations in the regime of strong nonlinearity and study effects such as pump depletion and corrections to the squeezing spectrum of the linearized model. We observe non-Gaussian states with Wigner function negativity and show that multimode interactions with the pump can act as decoherence channels

Nonlinear Quantum Behavior of Ultrashort-Pulse Optical Parametric Oscillators

The quantum features of ultrashort-pulse optical parametric oscillators (OPOs) are theoretically investigated in the nonlinear regime near and above threshold. Starting from basic premises of input-output theory, we derive a general quantum model for pulsed OPOs subject to χ(2) interactions between a multimode signal cavity and a non-resonant broadband pump field, elucidating time scale conditions required for such pulsed OPOs to admit an input-output description. By employing a supermode decomposition of the nonlinear Lindblad operators governing pump-signal interactions, we perform multimode quantum simulations in the regime of strong nonlinearity and study effects such as pump depletion and corrections to the squeezing spectrum of the linearized model. We observe non-Gaussian states with Wigner function negativity and show that multimode interactions with the pump can act as decoherence channels

Impact of Diabetes on Work Cessation: Data from the GAZEL cohort study

International audienceOBJECTIVE: To measure the impact of diabetes on work cessation, i.e., on the risks of work disability, early retirement, and death while in the labor force. RESEARCH DESIGN AND METHODS: We used data from the GAZEL prospective cohort of 20,625 employees of the French national gas and electricity company "EDF-GDF." We identified 506 employees with diabetes and randomly selected 2,530 nondiabetic employed control subjects matched for major sociodemographic and occupational characteristics. Using a multistate Cox model, we estimated hazard ratios (HRs) comparing the risks of transition from employment to disability, retirement, and death over time between participants with versus without diabetes. RESULTS: Employment rate decreased more rapidly in participants with diabetes (51.9 and 10.1% at 55 and 60 years, respectively) compared with nondiabetic participants (66.5 and 13.4%, respectively). Participants with diabetes had significantly increased risks of transition from employment to disability (HR 1.7 [95% CI 1.0-2.9]), retirement (HR 1.6 [1.5-1.8]), and death (HR 7.3 [3.6-14.6]) compared with participants without diabetes. Between 35 and 60 years, each participant with diabetes lost an estimated mean time of 1.1 year in the workforce (95% CI 0.99-1.14) compared with a nondiabetic participant. CONCLUSIONS: Our results provide evidence for a profound negative impact of diabetes on workforce participation in France. Social and economic consequences are major for patients, employers, and society-a burden that is likely to increase as diabetes becomes more and more common in the working-aged population

Glucocorticoid Compounds Modify Smoothened Localization and Hedgehog Pathway Activity

The Hedgehog signaling pathway is linked to a variety of diseases, notably a range of cancers. The first generation of drug screens identified Smoothened (Smo), a membrane protein essential for signaling, as an attractive drug target. Smo localizes to the primary cilium upon pathway activation, and this transition is critical for the response to Hedgehog ligands. In a high content screen directly monitoring Smo distribution in Hedgehog-responsive cells, we identified different glucocorticoids as specific modulators of Smo ciliary accumulation. One class promoted Smo accumulation, conferring cellular hypersensitivity to Hedgehog stimulation. In contrast, a second class inhibited Smo ciliary localization and signaling activity by both wild-type Smo, and mutant forms of Smo, SmoM2, and SmoD473H, that are refractory to previously identified Smo antagonists. These findings point to the potential for developing glucocorticoid-based pharmacological modulation of Smo signaling to treat mutated drug-resistant forms of Smo, an emerging problem in long-term cancer therapy. They also raise a concern about potential crosstalk of glucocorticoid drugs in the Hedgehog pathway, if therapeutic administration exceeds levels associated with on-target transcriptional mechanisms of glucocorticoid action.Chemistry and Chemical BiologyMolecular and Cellular BiologyStem Cell and Regenerative Biolog

Identity-by-descent filtering as a tool for the identification of disease alleles in exome sequence data from distant relatives

Large-scale, deep resequencing may be the next logical step in the genetic investigation of common complex diseases. Because each individual is likely to carry many thousands of variants, the identification of causal alleles requires an efficient strategy to reduce the number of candidate variants. Under many genetic models, causal alleles can be expected to reside within identity-by-descent (IBD) regions shared by affected relatives. In distant relatives, IBD regions constitute a small portion of the genome and can thus greatly reduce the search space for causal alleles. However, the effectiveness of this strategy is unknown. We test the simulated mini-exome data set in extended pedigrees provided by Genetic Analysis Workshop 17. At the fourth- and fifth-degree level of relatedness, case-case pairs shared between 1% and 9% of the genome identical by descent. As expected, no genes were shared identical by descent by all case subjects, but 43 genes were shared by many case subjects across at least 50 replicates. We filtered variants in these genes based on population frequency, function, informativeness, and evidence of association using the family-based association test. This analysis highlighted five genes previously implicated in triglyceride, lipid, and cholesterol metabolism. Comparison with the list of true risk alleles revealed that strict IBD filtering followed by association testing of the rarest alleles was the most sensitive strategy. IBD filtering may be a useful strategy for narrowing down the list of candidate variants in exome data, but the optimal degree of relatedness of affected pairs will depend on the genetic architecture of the disease under study

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior