Octave Spanning Frequency Comb on a Chip

Optical frequency combs have revolutionized the field of frequency metrology within the last decade and have become enabling tools for atomic clocks, gas sensing and astrophysical spectrometer calibration. The rapidly increasing number of applications has heightened interest in more compact comb generators. Optical microresonator based comb generators bear promise in this regard. Critical to their future use as 'frequency markers', is however the absolute frequency stabilization of the optical comb spectrum. A powerful technique for this stabilization is self-referencing, which requires a spectrum that spans a full octave, i.e. a factor of two in frequency. In the case of mode locked lasers, overcoming the limited bandwidth has become possible only with the advent of photonic crystal fibres for supercontinuum generation. Here, we report for the first time the generation of an octave-spanning frequency comb directly from a toroidal microresonator on a silicon chip. The comb spectrum covers the wavelength range from 990 nm to 2170 nm and is retrieved from a continuous wave laser interacting with the modes of an ultra high Q microresonator, without relying on external broadening. Full tunability of the generated frequency comb over a bandwidth exceeding an entire free spectral range is demonstrated. This allows positioning of a frequency comb mode to any desired frequency within the comb bandwidth. The ability to derive octave spanning spectra from microresonator comb generators represents a key step towards achieving a radio-frequency to optical link on a chip, which could unify the fields of metrology with micro- and nano-photonics and enable entirely new devices that bring frequency metrology into a chip scale setting for compact applications such as space based optical clocks

A para-differential renormalization technique for nonlinear dispersive equations

For \alpha \in (1,2) we prove that the initial-value problem \partial_t u+D^\alpha\partial_x u+\partial_x(u^2/2)=0 on \mathbb{R}_x\times\mathbb{R}_t; u(0)=\phi, is globally well-posed in the space of real-valued L^2-functions. We use a frequency dependent renormalization method to control the strong low-high frequency interactions.Comment: 42 pages, no figure

Precipitation and temperature ensemble forecasts from single-value forecasts

International audienceA procedure is presented to construct ensemble forecasts from single-value forecasts of precipitation and temperature. This involves dividing the spatial forecast domain and total forecast period into a number of parts that are treated as separate forecast events. The spatial domain is divided into hydrologic sub-basins. The total forecast period is divided into time periods, one for each model time step. For each event archived values of forecasts and corresponding observations are used to model the joint distribution of forecasts and observations. The conditional distribution of observations for a given single-value forecast is used to represent the corresponding probability distribution of events that may occur for that forecast. This conditional forecast distribution subsequently is used to create ensemble members that vary in space and time using the "Schaake Shuffle" (Clark et al, 2004). The resulting ensemble members have the same space-time patterns as historical observations so that space-time joint relationships between events that have a significant effect on hydrological response tend to be preserved. Forecast uncertainty is space and time-scale dependent. For a given lead time to the beginning of the valid period of an event, forecast uncertainty depends on the length of the forecast valid time period and the spatial area to which the forecast applies. Although the "Schaake Shuffle" procedure, when applied to construct ensemble members from a time-series of single value forecasts, may preserve some of this scale dependency, it may not be sufficient without additional constraint. To account more fully for the time-dependent structure of forecast uncertainty, events for additional "aggregate" forecast periods are defined as accumulations of different "base" forecast periods. The generated ensemble members can be ingested by an Ensemble Streamflow Prediction system to produce ensemble forecasts of streamflow and other hydrological variables that reflect the meteorological uncertainty. The methodology is illustrated by an application to generate temperature and precipitation ensemble forecasts for the American River in California. Parameter estimation and dependent validation results are presented based on operational single-value forecasts archives of short-range River Forecast Center (RFC) forecasts and medium-range ensemble mean forecasts from the National Weather Service (NWS) Global Forecast System (GFS)

miR-29b and miR-198 overexpression in CD8⁺ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction

Background: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells. Methods: We investigated gene expression profiles of tumor-reactive CD8+ T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8+ T cells from 25 RCC patients compared to 15 healthy volunteers. Results: We observed that CD8+ T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8+ T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8+ T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Conclusions: Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8+ T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo

Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial

Abstract Introduction Benzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients. Methods In this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis. Results Of the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11). Conclusions In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results. Trial Registration NCT00095251

A solution of the coincidence problem based on the recent galactic core black hole mass density increase

A mechanism capable to provide a natural solution to two major cosmological problems, i.e. the cosmic acceleration and the coincidence problem, is proposed. A specific brane-bulk energy exchange mechanism produces a total dark pressure, arising when adding all normal to the brane negative pressures in the interior of galactic core black holes. This astrophysically produced negative dark pressure explains cosmic acceleration and why the dark energy today is of the same order to the matter density for a wide range of the involved parameters. An exciting result of the analysis is that the recent rise of the galactic core black hole mass density causes the recent passage from cosmic deceleration to acceleration. Finally, it is worth mentioning that this work corrects a wide spread fallacy among brane cosmologists, i.e. that escaping gravitons result to positive dark pressure.Comment: 14 pages, 3 figure

Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. Results Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p \u3c 0.01) and EMRA (B = 2.90, p \u3c 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p \u3c 0.05) after applying similar adjustments. No associations were observed in CMV− individuals. Conclusions/interpretation The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Effective numerical simulation of the Klein–Gordon–Zakharov system in the Zakharov limit

Solving the Klein-Gordon-Zakharov (KGZ) system in the high-plasma frequency regime $c\gg1$ is numerically severely challenging due to the highly oscillatory nature or the problem. To allow reliable approximations classical numerical schemes require severe step size restrictions depending on the small parameter $c^{−2}$ . This leads to large errors and huge computational costs. In the singular limit $c\to\infty$ the Zakharov system appears as the regular limit system for the KGZ system. It is the purpose of this paper to use this approximation in the construction of an effective numerical scheme for the KGZ system posed on the torus in the highly oscillatory regime $c\gg1$. The idea is to filter out the highly oscillatory phases explicitly in the solution. This allows us to play back the numerical task to solving the non-oscillatory Zakharov limit system. The latter can be solved very efficiently without any step size restrictions. The numerical approximation error is then estimated by showing that solutions of the KGZ system in this singular limit can be approximated via the solutions of the Zakharov system and by proving error estimates for the numerical approximation of the Zakharov system. We close the paper with numerical experiments which show that this method is more effective than other methods in the high-plasma frequency regime $c\gg1$

From Stalingrad to Grozny: Patriotism, political pressure, and literature in the war reporting of Vassily Grossman and Anna Politkovskaya

Comparing the work of the 20th century Soviet journalist and writer, Vassily Grossman, with that of his compatriot, Anna Politkovskaya, almost half a century later, this article examines the two journalists’ writing for what it tells us about the changing nature of Russian journalism, and reporter involvement in the coverage of war. Grossman was reporting on his country’s fight for survival in a war with Nazi Germany; Politkovskaya had no peer in her coverage of the bloodiest consequence of the collapse of that country, the Soviet Union: the wars in Chechnya. It also considers the literary nature of Grossman and Politkovskaya’s reporting. The article argues that the two journalists’ work has significance far beyond the time when they were reporting, and should therefore be more widely read and studied for what it tells us about covering conflict, and especially civilian suffering and, in the case of Politkovskaya, counter-insurgency