Cavity Quantum Optomechanical Nonlinearities and Position Measurement beyond the Breakdown of the Linearized Approximation.

Several optomechanics experiments are now entering the highly sought nonlinear regime where optomechanical interactions are large even for low light levels. Within this regime, new quantum phenomena and improved performance may be achieved; however, a corresponding theoretical formalism of cavity quantum optomechanics that captures the nonlinearities of both the radiation-pressure interaction and the cavity response is needed to unlock these capabilities. Here, we develop such a nonlinear cavity quantum optomechanical framework, which we then utilize to propose how position measurement can be performed beyond the breakdown of the linearized approximation. Our proposal utilizes optical general-dyne detection, ranging from single to dual homodyne, to obtain mechanical position information imprinted onto both the optical amplitude and phase quadratures and enables both pulsed and continuous modes of operation. These cavity optomechanical nonlinearities are now being confronted in a growing number of experiments, and our framework will allow a range of advances to be made in, e.g., quantum metrology, explorations of the standard quantum limit, and quantum measurement and control.

Generation of squeezed light vacuum enabled by coherent population trapping.

We demonstrate the possibility to generate squeezed vacuum states of light by four wave mixing (FWM) enabled coherent population trapping in a metastable helium cell at room temperature. Contrary to usual FWM far detuned schemes, we work at resonance with an atomic transition. We investigate the properties of such states and show that the noise variances of the squeezed and anti-squeezed quadratures cannot be explained by the simple presence of losses. A specific model allows us to demonstrate the role played by spontaneous emitted photons, which experience squeezing while propagation inside of the cell. This theoretical model, which takes into account both residual absorption and spontaneous emission, leads to an excellent agreement with the experimental data without any adjusted parameter.

[Surgical management of suburethral sling complications and functional outcomes]. / Prise en charge chirurgicale des complications de bandelette sous-urétrale et résultats fonctionnels.

OBJECTIVES: To identify various clinical presentation leading to the diagnosis of mid-urethral sling (MUS) complications and to analyze the functional outcomes after surgical management of these complications. METHOD: Retrospective observational monocentric study of all patients treated by MUS section or removal, between December 2005 and October 2019, in a pelviperineology centre. RESULTS: During this study, 96 patients were included. MUS complications surgically managed were vaginal mesh exposure (48 %), urethral mesh exposure (17 %), bladder mesh exposure (10 %); dysuria (30 %), pain (6 %), and infection (3 %). The mean time to diagnosis was 2 years. This diagnosis delay was caused by a non-specific and heterogeneous symptomatology. Surgical management consisted in MUS partial removal (79 %) and MUS simple section (21 %) with low perioperative morbidity. At three months follow-up, 36 patients (53 %) had stress urinary incontinence (SUI), including 13 (19 %) de novo (meaning no SUI before MUS section/removal) and 19 (28 %) had overactive bladder, including 9 (13 %) de novo. Half of the patients with SUI after MUS section/removal were able to be treated by a second MUS with a success rate of 83 % at 3 years. CONCLUSION: Clinical presentation of MUS complications is heterogeneous. Surgical treatment was associated with low morbidity in our study. Post-operatively, half of the patients had SUI and a second MUS was a relevant treatment option after proper evaluation. LEVEL OF EVIDENCE: 4.

Coherent Population Oscillation-Based Light Storage.

We theoretically study the propagation and storage of a classical field in a Λ-type atomic medium using coherent population oscillations (CPOs). We show that the propagation eigenmodes strongly relate to the different CPO modes of the system. Light storage in such modes is discussed by introducing a "populariton" quantity, a mixture of populations and field, by analogy to the dark state polariton used in the context of electromagnetically induced transparency light storage protocol. As experimentally shown, this memory relies on populations and is then-by contrast with usual Raman coherence optical storage protocols-robust to dephasing effects.

Towards an open grapevine information system.

Viticulture, like other fields of agriculture, is currently facing important challenges that will be addressed only through sustained, dedicated and coordinated research. Although the methods used in biology have evolved tremendously in recent years and now involve the routine production of large data sets of varied nature, in many domains of study, including grapevine research, there is a need to improve the findability, accessibility, interoperability and reusability (FAIR-ness) of these data. Considering the heterogeneous nature of the data produced, the transnational nature of the scientific community and the experience gained elsewhere, we have formed an open working group, in the framework of the International Grapevine Genome Program (www.vitaceae.org), to construct a coordinated federation of information systems holding grapevine data distributed around the world, providing an integrated set of interfaces supporting advanced data modeling, rich semantic integration and the next generation of data mining tools. To achieve this goal, it will be critical to develop, implement and adopt appropriate standards for data annotation and formatting. The development of this system, the GrapeIS, linking genotypes to phenotypes, and scientific research to agronomical and oeneological data, should provide new insights into grape biology, and allow the development of new varieties to meet the challenges of biotic and abiotic stress, environmental change, and consumer demand.

Phase-sensitive amplification via coherent population oscillations in metastable helium at room temperature.

In this Letter, we report our experimental results on phase-sensitive amplification (PSA) in a nondegenerate signal-idler configuration using ultranarrow coherent population oscillations in metastable helium at room temperature. We achieved a high PSA gain of nearly 7 with a bandwidth of 200 kHz by using the system at resonance in a single-pass scheme. Further, the measured minimum gain is close to the ideal value, showing that we have a nearly pure PSA. This is also confirmed from our phase-to-phase transfer curves measurements, illustrating that we have a nearly perfect squeezer, which is interesting for a variety of applications.

Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases.

MicroRNAs (miRNAs) carry out post-transcriptional control of a multitude of cellular processes. Aberrant expression of miRNA can lead to diseases, including cancer. Gliomas are aggressive brain tumors that are thought to arise from transformed glioma-initiating neural stem cells (giNSCs). With the use of giNSCs and human glioblastoma cells, we investigated the function of miRNAs in gliomas. We identified pro-neuronal miR-128 as a candidate glioma tumor suppressor miRNA. Decreased expression of miR-128 correlates with aggressive human glioma subtypes. With a combination of molecular, cellular and in vivo approaches, we characterize miR-128's tumor suppressive role. miR-128 represses giNSC growth by enhancing neuronal differentiation. miR-128 represses growth and mediates differentiation by targeting oncogenic receptor tyrosine kinases (RTKs) epithelial growth factor receptor and platelet-derived growth factor receptor-α. Using an autochthonous glioma mouse model, we demonstrated that miR-128 repressed gliomagenesis. We identified miR-128 as a glioma tumor suppressor that targets RTK signaling to repress giNSC self-renewal and enhance differentiation.

An integrated system to remote monitor and control anaerobic wastewater treatment plants through the internet.

The TELEMAC project brings new methodologies from the Information and Science Technologies field to the world of water treatment. TELEMAC offers an advanced remote management system which adapts to most of the anaerobic wastewater treatment plants that do not benefit from a local expert in wastewater treatment. The TELEMAC system takes advantage of new sensors to better monitor the process dynamics and to run automatic controllers that stabilise the treatment plant, meet the depollution requirements and provide a biogas quality suitable for cogeneration. If the automatic system detects a failure which cannot be solved automatically or locally by a technician, then an expert from the TELEMAC Control Centre is contacted via the internet and manages the problem.

[Kinetic changes of plasma IL-1 and IL-6 levels in MPTP-induced Parkinson's disease model mice and their relationship with brain asymmetry].

AIM: To set up Parkinson's disease (PD) model mice by using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), detect the levels of plasma IL-1 and IL-6, and to explore their relationship with brain asymmetry. METHODS: Male C57BL/6J mice were divided into right pawed mouse group and left pawed mouse group according to paw preference test which reflects brain asymmetry. Mice were injected intraperitoneally with 25 mg/kg MPTP each day for 5 consecutive days. The mice were executed and blood samples were taken at 1, 3 and 14 days after the last time injection. Control mice were only injected with normal saline. The levels of plasma IL-6 and IL-1 were detected by ELISA. RESULTS: Plasma IL-6 level in normal control mice was low, but elevated dramatically at 14 days after last time injection of MPTP in PD model mice. Furthermore, IL-6 level of right pawed mice was higher than that of left pawed mice. Plasma IL-1 levels also increased on day 3 after last time injection of MPTP, and the level of left pawed mice was higher than that of right pawed mice. CONCLUSION: IL-6 and IL-1 probably participate in the occurrence and progress of MPTP-induced PD in model mice, and were related with brain asymmetry.

Brain interleukin asymmetries and paw preference in mice.

The two sides of the brain are differently involved in the modulation of immune responses as demonstrated by lesion and behavioral approaches. To study the interactions between cerebral cortex cytokines and brain lateralization, three groups of BALB/c mice were selected on the basis of their performance in the paw preference test (left-pawed, ambidextrous and right-pawed) and the levels of interleukin-1beta and interleukin-6 were measured in the two cerebral cortices after an intraperitoneal saline or lipopolysaccharide. Generally, right cortices had higher interleukin-1beta and interleukin-6 levels than left cortices for both saline and lipopolysaccharide-treated mice. A strong correlation between the levels of interleukin-1beta and interleukin-6 in right and left cortices and behavioral lateralization was observed. For the saline-treated mice: in their left cortices, interleukin-1beta levels were higher for ambidextrous mice than for right-pawed mice (P<0.05); in their right cortices, interleukin-6 levels were higher for ambidextrous mice than for right-/left-pawed mice, and right-pawed mice have higher levels of interleukin-6 than left-pawed mice (P<0.01). In their left cortices, interleukin-6 levels are higher for left-pawed mice than for both ambidextrous and right-pawed mice (P<0.01). In their left cortices, interleukin-6 levels are higher for left-pawed mice than for both ambidextrous and right-pawed mice (P<0.01). The quadratic curve equations showed that the levels of interleukin-1beta and interleukin-6 in the right/left cortices had a highly significant correlation with paw preference scores in both normal and lipopolysaccharide-treated mice. In conclusion, the present report demonstrated that the basal levels of interleukin-1beta and interleukin-6 were higher in the right cortex than left cortex in mice. There was a strong correlation between the levels of interleukin-1beta and interleukin-6 and behavioral lateralization, and cytokine asymmetries had a strong correlation with the direction and the intensity of behavioral lateralization.

Suppression of restraint-induced plasma cytokines in mice pretreated with LPS.

A previous exposure to an inflammatory reaction is known to increase or decrease the activation of the hypothalamic-pituitary-adrenal (HPA) axis induced by a psychological/physical stress. Beside HPA activation, the non- specific responses to these two kinds of stresses involve the immune system including the production of cytokines. Therefore, they could interfere in cytokine production. In order to test this hypothesis, female C3H mice were first injected i.p. with 5 microg of lipopolysaccharide (LPS) or not (C). Eight days later, half of them were submitted to a 4 h-restraint (R) applied during the nocturnal part of the dark-light cycle and sacrificed immediately after (groups LPS-R and C-R), while the non restrained mice stayed in their home cages (groups LPS-C and C-C). Restraint induced an increase in corticosterone production that was not altered by the previous administration of LPS. It had no effect on mitogen-induced lymphoproliferation. However, restraint induced an augmentation of plasma concentrations of interleukin (IL)-1 and IL-6 that was not observed in animals previously exposed to LPS. These results show that restraint, which represents a psychological stress is able to induce the production of plasma cytokines in mice. They also suggest that LPS may induce a long lasting suppression of plasma cytokines through mechanisms that remain to be elucidated.

Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy.

Cytokine therapy for cancer or viral diseases is accompanied by the development of depressive symptoms in a significant proportion of patients. Despite the increasing number of studies on the neurotoxic effects of cytokines, the mechanisms by which cytokines induce depressive symptoms remain largely unknown. In view of the relationship between neurotransmitter precursors and mood, the present study aimed at assessing the relationship between serum concentrations of the amino acids tryptophan and tyrosine, major precursors of serotonin and norepinephrine respectively, and depressive symptoms in cancer patients undergoing cytokine therapy. Sixteen cancer patients eligible to receive immunotherapy with interleukin-2 and/or interferon-alpha participated in the study. At baseline and after one week and one month of therapy, depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), and blood samples were collected for the determination of the large neutral amino acids (LNAA) (tryptophan, tyrosine, valine, leucine, isoleucine, phenylalanine) which compete for transport across the blood-brain barrier. Serum concentrations of tryptophan as well as the tryptophan/LNAA ratio significantly decreased between baseline, one week and one month of therapy. The development and severity of depressive symptoms, especially anorexia, pessimistic thoughts, suicidal ideation and loss of concentration were positively correlated with the magnitude of the decreases in tryptophan concentrations during treatment. These findings indicate that the development of depressive symptoms in patients undergoing cytokine therapy could be mediated by a reduced availability of the serotonin relevant amino acid precursor, tryptophan.

Modelisation of an unspecialized quadruped walking mammal.

Kinematics and structural analyses were used as basic data to elaborate a dynamic quadruped model that may represent an unspecialized mammal. Hedgehogs were filmed on a treadmill with a cinefluorographic system providing trajectories of skeletal elements during locomotion. Body parameters such as limb segments mass and length, and segments centre of mass were checked from cadavers. These biological parameters were compiled in order to build a virtual quadruped robot. The robot locomotor behaviour was compared with the actual hedgehog to improve the model and to disclose the necessary changes. Apart from use in robotics, the resulting model may be useful to simulate the locomotion of extinct mammals.

Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy.

The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.

Lowered serum dipeptidyl peptidase IV activity is associated with depressive symptoms and cytokine production in cancer patients receiving interleukin-2-based immunotherapy.

There is some evidence that treatment with interleukin-2 (IL-2) and interferon-alpha (IFNalpha) frequently induces depressive symptoms and activation of the inflammatory response system (IRS). There is evidence that major depression is accompanied by lowered serum activity of dipeptidyl peptidase IV (DPP IV; EC 3.4.14.5), a membrane-bound serine protease which catalyses the cleavage of some cytokines and neuro-active peptides and which modulates T cell activation and the production of cytokines, such as IL-2. This study was carried out to examine the effects of immunochemotherapy with IL-2 and IFNalpha, alone and together, in cancer patients on serum DPP IV activity in relation to changes in depressive symptoms and the IRS. The Montgomery and Asberg Rating Scale (MADRS), serum DPP IV activity, and the serum IL-6, and IL-2 receptor (IL-2R) concentrations were measured in 26 patients with metastatic cancers before and three and five days after treatment with IL-2 and IFNalpha, alone or together. Treatment with IL-2 with or without IFNalpha significantly suppressed serum DPP IV activity. The MADRS scores were significantly elevated by treatment with IL-2 with or without IFNalpha, but not IFNalpha alone. The immunochemotherapy-induced decreases in serum DPP IV were significantly and inversely correlated with the increases in the MADRS. Treatment with IL-2 alone or combined with IFNalpha also elevated serum IL-6 and IL-2R. There were significant and inverse correlations between the immuchemotherapy-induced decreases in serum DPP IV and the elevations in serum IL-6 or IL-2R. In conclusion, treatment with IL-2/IFNalpha decreases serum DPP IV activity within 3-5 days and the immunochemotherapy-induced decreases in serum DPP IV activity are significantly and inversely related to treatment-induced increases in severity of depression and signs of activation of the IRS.

Physiological significance of the interleukin 1 receptor accessory protein.

Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal-transducing component of the IL-1 receptor type I. The recent availability of IL-1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP. Animals were injected intraperitoneally with rat recombinant IL-1beta (200 ng/mouse), lipopolysaccharide (LPS, 5 microg/mouse), or subjected to 1-hour restraint stress. Neuroendocrine and immune parameters were measured 2 h after IL-1 or LPS injection or just after restraint. In wild-type controls, IL-1 and LPS activated the hypothalamic-pituitary-adrenal axis and increased plasma IL-6. In KO mice, the plasma levels of corticosterone and IL-6 increased after LPS, but not after rat recombinant IL-1beta. The LPS-induced depression of the lymphoproliferation was similar in wild-type and KO mice. Finally, the 1-hour restraint was able to increase the plasma levels of corticosterone in KO mice. These results show that IL-1RAcP is essential for physiological activities of peripheral IL-1, as it was previously demonstrated for those of brain IL-1. However, using IL-1RAcP KO mice, we were unable to demonstrate a specific role of endogenous IL-1 during LPS-induced inflammation. Moreover, stress-induced activation of the hypothalamic-pituitary-adrenal axis may occur in the absence of the IL-1-transducing receptor, IL-1RAcP.

Interleukin 1 receptor accessory protein (IL-1RAcP) is necessary for centrally mediated neuroendocrine and immune responses to IL-1beta.

Mice deficient for the IL-1RAcP gene (IL-1RAcP KO) were used to explore the role of IL-1RAcP in physiological functions of brain IL-1beta. Animals were injected i.c.v. with two different doses of recombinant human (rh) IL-1beta: a small one (750 pg) known to induce sickness behavior, and a larger one (50 ng), chosen to counteract the possible loss of affinity of IL-1beta on its receptor. Neuroendocrine and immune parameters were measured 2 h after IL-1 injection. The increase of plasma corticosterone induced by rhIL-1beta in wild-type (WT) mice was not observed in IL-1RAcP KO mice. Likewise, the depression of splenocyte proliferation occurred in WT but not in KO mice. Finally, in opposition to WT mice, plasma levels and brain cortical content of IL-6 in IL-1RAcP KO mice remained unchanged as compared to saline-injected controls. The results clearly demonstrate that IL-1RAcP is necessary for the induction of the main neuroendocrine and immune effects of central IL-1beta.

Strain-dependent association between lateralization and lipopolysaccharide- induced IL-1beta and IL-6 production in mice.

OBJECTIVE: The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mouse. We predicted that the production of cytokines, which are one of the molecular pathways for brain-immune interactions, should be linked to lateralization in a strain-dependent manner. METHODS: We therefore measured plasma levels of interleukin (IL)-1beta and IL-6 after an intraperitoneal injection of lipopolysaccharide (LPS) in two strains of mice (C3H and BALB/c) that were selected for their different profiles of cytokine production. RESULTS: Plasma levels of IL-1beta and IL-6 increased after LPS injection in both strains and this increase was dependent on paw preference in BALB/c but not in C3H mice. Increased levels of IL-1beta were observed in left-pawed and ambidextrous but not in right-pawed mice. For IL-6, the LPS-induced increase was higher in ambidextrous than in left- and right-pawed animals. CONCLUSION: Cytokines may represent one of the factors responsible for interindividual differences in brain-immune interactions.

Activation of the hypothalamic-pituitary-adrenal axis in IL-1 beta-converting enzyme-deficient mice.

Interleukin-1beta (IL-1beta) plays a key role in immune, behavioral and neuroendocrine responses to inflammation or infection. IL-1beta could also be involved in the response of the hypothalamic-pituitary-adrenal (HPA) axis during stress. Mature IL-1beta derives from a 31-kD precursor (pro-IL-1beta) that is processed by IL-1beta-converting enzyme (ICE). Mice in which the ICE gene has been nullated by homologous recombination were used to investigate the role of IL-1beta in the HPA axis response. Plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) in response to an intraperitoneal injection of 5 microg lipopolysaccharide (LPS) were similar in ICE-deficient mice and wild-type (WT) controls. In contrast, plasma ACTH response to restraint or to 200 ng of rat recombinant IL-1beta (rrIL-1beta) was higher in ICE-deficient mice as compared to WT animals. This hyperreactivity of the HPA axis in ICE knockout mice appears not to be related to the production of plasma IL-1beta or IL-6, which was similar to that of WT mice after rrIL-1beta injection. After lipopolysaccharide, ICE-deficient mice exhibited a smaller increase in plasma-immunoreactive IL-1beta and IL-6 as compared to WT controls. After restraint stress neither increase in plasma IL-1beta nor IL-6 was observed. The mechanisms responsible for the increased reactivity of the HPA axis in ICE-deficient mice may result from a higher sensitivity of the HPA axis to inflammatory cytokines or to cleavage products of pro-IL-1beta processed by non-ICE proteases.