Astrophysique Relativiste, Théories, Expériences, Métrologie, Instrumentation, Signaux

DNA methyltransferase I (Dnmt1), the maintenance enzyme for DNA cytosine methylation, is expressed at high levels in the CNS during embryogenesis and after birth. Because embryos deficient for Dnmt1 die at gastrulation, the role of Dnmt1 in the development and function of the nervous system could not be studied by using this mutation. We therefore used the cre/loxP system to produce conditional mutants that lack Dnmt1 in neuroblasts of embryonic day 12 embryos or in postmitotic neurons of the postnatal animal. Conditional deletion of the Dnmt1 gene resulted in rapid depletion of Dnmt1 proteins, indicating that the enzyme in postmitotic neurons turns over quickly. Dnmt1 deficiency in postmitotic neurons neither affected levels of global DNA methylation nor influenced cell survival during postnatal life. In contrast, Dnmt1 deficiency in mitotic CNS precursor cells resulted in DNA hypomethylation in daughter cells. Whereas mutant embryos carrying 95% hypomethylated cells in the brain died immediately after birth because of respiratory distress, mosaic animals with 30% hypomethylated CNS cells were viable into adulthood. However, these mutant cells were eliminated quickly from the brain within 3 weeks of postnatal life. Thus, hypomethylated CNS neurons were impaired functionally and were selected against at postnatal stages.

The subdivision of the lateral mesoderm into a visceral (splanchnic) and a somatic layer is a crucial event during early mesoderm development in both arthropod and vertebrate embryos. In Drosophila, this subdivision leads to the differential development of gut musculature versus body wall musculature. Here we report that biniou, the sole Drosophila representative of the FoxF subfamily of forkhead domain genes, has a key role in the development of the visceral mesoderm and the derived gut musculature. biniou expression is activated in the trunk visceral mesoderm primordia downstream of dpp, tinman, and bagpipe and is maintained in all types of developing gut muscles. We show that biniou activity is essential for maintaining the distinction between splanchnic and somatic mesoderm and for differentiation of the splanchnic mesoderm into midgut musculature. biniou is required not only for the activation of differentiation genes that are expressed ubiquitously in the trunk visceral mesoderm but also for the expression of dpp in parasegment 7, which governs proper midgut morphogenesis. Activation of dpp is mediated by specific Biniou binding sites in a dpp enhancer element, which suggests that Biniou serves as a tissue-specific cofactor of homeotic gene products in visceral mesoderm patterning. Based upon these and other data, we propose that the splanchnic mesoderm layers in Drosophila and vertebrate embryos are homologous structures whose development into gut musculature and other visceral organs is critically dependent on FoxF genes.

Abstract Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT 2A receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT 2A -Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT 2A -selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT 2A -Gq but not 5-HT 2A -β-arrestin2 recruitment efficacy predicts psychedelic potential, assessed using head-twitch response (HTR) magnitude in male mice. We further show that disrupting Gq-PLC signaling attenuates the HTR and a threshold level of Gq activation is required to induce psychedelic-like effects, consistent with the fact that certain 5-HT 2A partial agonists (e.g., lisuride) are non-psychedelic. Understanding the role of 5-HT 2A Gq-efficacy in psychedelic-like psychopharmacology permits rational development of non-psychedelic 5-HT 2A agonists. We also demonstrate that β-arrestin-biased 5-HT 2A receptor agonists block psychedelic effects and induce receptor downregulation and tachyphylaxis. Overall, 5-HT 2A receptor Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics.

OBJECTIVE: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics (PK) of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients. METHOD: This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32 mg delivered dose, N = 63) or TAcs (1 mL, 40 mg, N = 18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week 1, Week 6, Week 12, Week 16 or Week 20; TAcs: Week 6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means (GMs)), PK (non-compartmental analysis models), and adverse events (AEs) were assessed. RESULTS: SF TA concentrations following FX006 were quantifiable through Week 12 (pg/mL: 231,328.9 at Week 1; 3590.0 at Week 6; 290.6 at Week 12); post-TAcs, only two of eight patients had quantifiable SF TA at Week 6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 h and slowly declined to <110 pg/mL over Weeks 12-20; following TAcs, plasma TA peaked at 4 h (9628.8 pg/mL), decreased to 4991.1 pg/mL at 24 h, and was 149.4 pg/mL at Week 6, the last post-treatment time point assessed. AEs were similar between groups. CONCLUSION: In knee OA patients, microsphere-based TA delivery via a single IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs.

In this paper we introduce a real-time obstacle detection and classification system designed to assist visually impaired people to navigate safely, in indoor and outdoor environments, by handling a smartphone device. We start by selecting a set of interest points extracted from an image grid and tracked using the multiscale Lucas - Kanade algorithm. Then, we estimate the camera and background motion through a set of homographic transforms. Other types of movements are identified using an agglomerative clustering technique. Obstacles are marked as urgent or normal based on their distance to the subject and the associated motion vector orientation. Following, the detected obstacles are fed/sent to an object classifier. We incorporate HOG descriptor into the Bag of Visual Words (BoVW) retrieval framework and demonstrate how this combination may be used for obstacle classification in video streams. The experimental results demonstrate that our approach is effective in image sequences with significant camera motion and achieves high accuracy rates, while being computational efficient.

Abstract This paper outlines the roadmap towards the redefinition of the second, which was recently updated by the CCTF Task Force created by the CCTF in 2020. The main achievements of optical frequency standards (OFS) call for reflection on the redefinition of the second, but open new challenges related to the performance of the OFS, their contribution to time scales and UTC, the possibility of their comparison, and the knowledge of the Earth’s gravitational potential to ensure a robust and accurate capacity to realize a new definition at the level of 10 −18 uncertainty. The mandatory criteria to be achieved before redefinition have been defined and their current fulfilment level is estimated showing the fields that still needed improvement. The possibility to base the redefinition on a single or on a set of transitions has also been evaluated. The roadmap indicates the steps to be followed in the next years to be ready for a sound and successful redefinition.

RNA interference through the expression of small hairpin RNA (shRNA) molecules has become a very promising tool in reverse mouse genetics as it may allow inexpensive and rapid gene function analysis in vivo. However, the prerequisites for ubiquitous and reproducible shRNA expression are not well defined. Here we show that a single copy shRNA-transgene can mediate body-wide gene silencing in mice when inserted in a defined locus of the genome. The most commonly used promoters for shRNA expression, H1 and U6, showed a comparably broad activity in this configuration. Taken together, the results define a novel approach for efficient interference with expression of defined genes in vivo. Moreover, we provide a rapid strategy for the production of gene knockdown mice combining recombinase mediated cassette exchange and tetraploid blastocyst complementation approaches.

RNA interference through expression of short hairpin (sh)RNAs provides an efficient approach for gene function analysis in mouse genetics. Techniques allowing to control time and degree of gene silencing in vivo, however, are still lacking. Here we provide a generally applicable system for the temporal control of ubiquitous shRNA expression in mice. Depending on the dose of the inductor doxycycline, the knockdown efficiency reaches up to 90%. To demonstrate the feasibility of our tool, a mouse model of reversible insulin resistance was generated by expression of an insulin receptor (Insr)-specific shRNA. Upon induction, mice develop severe hyperglycemia within seven days. The onset and progression of the disease correlates with the concentration of doxycycline, and the phenotype returns to baseline shortly after withdrawal of the inductor. On a broad basis, this approach will enable new insights into gene function and molecular disease mechanisms.

Estimating the parameters of gravitational wave signals detected by ground-based detectors requires an understanding of the properties of the detectors' noise. In particular, the most commonly used likelihood function for gravitational wave data analysis assumes that the noise is Gaussian, stationary, and of known frequency-dependent variance. The variance of the colored Gaussian noise is used as a whitening filter on the data before computation of the likelihood function. In practice the noise variance is not known and it evolves over timescales of dozens of seconds to minutes. We study two methods for estimating this whitening filter for ground-based gravitational wave detectors with the goal of performing parameter estimation studies. The first method uses large amounts of data separated from the specific segment we wish to analyze and computes the power spectral density of the noise through the mean-median Welch method. The second method uses the same data segment as the parameter estimation analysis, which potentially includes a gravitational wave signal, and obtains the whitening filter through a fit of the power spectrum of the data in terms of a sum of splines and Lorentzians. We compare these two methods and conclude that the latter is a more effective spectral estimation method as it is quantitatively consistent with the statistics of the data used for gravitational wave parameter estimation while the former is not. We demonstrate the effect of the two methods by finding quantitative differences in the inferences made about the physical properties of simulated gravitational wave sources added to LIGO-Virgo data.

GRB 130925A is a peculiar event characterized by an extremely long gamma-ray duration ($\approx$7 ks), as well as dramatic flaring in the X-rays for $\approx$20 ks. After this period, its X-ray afterglow shows an atypical soft spectrum with photon index $\Gamma$$\sim$4, as observed by Swift and Chandra, until $\approx 10^7$ s, when XMM-Newton observations uncover a harder spectral shape with $\Gamma$$\sim$2.5, commonly observed in GRB afterglows. We find that two distinct emission components are needed to explain the X-ray observations: a thermal component, which dominates the X-ray emission for several weeks, and a non-thermal component, consistent with a typical afterglow. A forward shock model well describes the broadband (from radio to X-rays) afterglow spectrum at various epochs. It requires an ambient medium with a very low density wind profile, consistent with that expected from a low-metallicity blue supergiant (BSG). The thermal component has a remarkably constant size and a total energy consistent with those expected by a hot cocoon surrounding the relativistic jet. We argue that the features observed in this GRB (its ultralong duration, the thermal cocoon, and the low density wind environment) are associated with a low metallicity BSG progenitor and, thus, should characterize the class of ultralong GRBs.

A new LISA simulator (LISACode) is presented. Its ambition is to achieve a new degree of sophistication allowing to map, as closely as possible, the impact of the different subsystems on the measurements. LISACode is not a detailed simulator at the engineering level but rather a tool whose purpose is to bridge the gap between the basic principles of LISA and a future, sophisticated end-to-end simulator. This is achieved by introducing, in a realistic manner, most of the ingredients that will influence LISA's sensitivity as well as the application of TDI combinations. Many user-defined parameters allow the code to study different configurations of LISA thus helping to finalize the definition of the detector. Another important use of LISACode is in generating time-series for data analysis developments.

This paper addresses the issue of 3D mesh indexation by using shape descriptors (SDs) under constraints of geometric and topological invariance. A new shape descriptor, the canonical 3D Hough transform descriptor (C3DHTD) is here proposed. Intrinsically topologically stable, the C3DHTD is not invariant to geometric transformations. Nevertheless, we show mathematically how the C3DHTD can be optimally associated (in terms of compactness of representation and computational complexity) with a spatial alignment procedure which leads to a geometric invariant behavior. Experiments carried out upon the categorized MPEG-7 3D model database objectively show that the C3DHTD outperforms both the MPEG-7 3D SD and classic EGIs descriptor.

The Mock LISA data challenges are a program to demonstrate LISA dataanalysis capabilities and to encourage their development. Each round of challenges consists of several data sets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants are asked to analyze the data sets and report the maximum information about the source parameters. The challenges are being released in rounds of increasing complexity and realism: here we present the results of Challenge 2, issued in Jan 2007, which successfully demonstrated the recovery of signals from nonspinning supermassive-black-hole binaries with optimal SNRs between 10 and 2000, from 20 000 overlapping galactic white-dwarf binaries (among a realistically distributed population of 26 million), and from the extreme-massratio inspirals of compact objects into central galactic black holes with optimal SNRs 100.

The assessment of residential exposure to agricultural pesticides is a major issue for public health, regulatory and management purposes. In recent years, research into this field has developed considerably. The purpose of this scoping review is to provide an overview of scientific literature characterizing residential exposure to agricultural pesticides and to identify potential gaps in this research area. This work was conducted according to the JBI and PRISMA guidelines. Three databases were consulted. At least two experts selected the eligible studies. Our scoping review enabled us to identify 151 articles published between 1988 and 2019 dealing with the assessment of residential exposure to agricultural pesticides. Of these, 98 (64.9%) were epidemiological studies investigating possible links between pesticide exposure and the onset of adverse health effects, principally cancers and reproductive outcomes. They predominantly used Geographic Information Systems and sometimes surveys or interviews to calculate surrogate exposure metrics, the most common being the amounts of pesticides applied or the surface area of crops around the dwelling. Twenty-six (17.2%) were observational measurement studies conducted to quantify levels of pesticide exposure and identify their possible determinants. These studies assessed exposure by measuring pesticides in biological and environmental matrices, mostly in urines and house dust. Finally, we found only eight publications (5.3%) that quantified the risk to human health due to residential exposure for management purposes, in which exposure was mainly determined using probabilistic models. Pesticide exposure appears to be largely correlated with the spatial organization of agriculture activities in a territory. The determinants and routes of exposure remain to be explored to improve the conduct of epidemiological and risk assessment studies and to help prevent future exposures. Improvement could be expected from small-scale studies combining different methods of exposure assessment.

We present a generic and robust method for model-based global 3D head pose estimation in monocular and non-calibrated video sequences. The proposed method relies on a 3D/2D matching between 2D image features estimated throughout the sequence and 3D object features of a generic head model. Specifically, it combines motion and texture features in an iterative optimization procedure based on the downhill simplex algorithm. A proper initialization of the pose parameters, based on a block matching procedure, is performed at each frame in order to take into account large amplitude motions. For the same reason, we have developed a nonlinear optical flow-based interpolation algorithm for increasing the frame rate. Experiments demonstrate that this method is stable over extended sequences including large head motions, occlusions, various head postures and lighting variations. The estimation accuracy is related to the head model, as established by using an ellipsoidal model and an ad hoc synthesized model. The proposed method is general enough to be applied to other tracking applications.

This paper presents a new compression technique for 3D dynamic meshes, referred to as FAMC - frame-based animated mesh compression, recently promoted within the MPEG-4 standard as Amendment 2 of part 16 AFX (Animation Framework extension). The heart of the method is a skinning model optimally computed from a frame-based representation and exploited for compression purposes within the framework of a motion compensation strategy. The proposed encoder offers high compression performances (gains in bitrate of 60% with respect to the previous MPEG-4 technique and of 20 to 40% with respect to state-of-the-art approaches) and is well suited for compressing both geometric and photometric attributes.

This thesis deals with the vehicle routing problem which is the problem of designing optimal routes of vehicles from a depot to a set of customers. Up to now, only heuristic methods have been used in practice. In this work, we focus on the polyhedral approach of the problem, it means on an exact method based on the polyhedral representation of the convex hull of feasible solutions. More precisely, we present a "Branch and Cut" algorithm for the classical vehicle routing problem with any unsplitable demands and identical vehicles located in a same depot. The originality of our work appears in three points : i) the discovery of new valid inequalities ; ii) separation methods for these inequalities ; iii) a "Branch and Cut" algorithm which combines the use of these methods with new enumeration strategies. This algorithm allows us to solve many instances from the literature, some of them which have never been solved to optimality before.

In this letter, we propose a new definition of the discrete time and frequency Wigner-Ville distribution. The proposed distribution not only displays a readable representation (small aliasing) but also exhibits unitarity and is easy to compute. We compare the time-frequency representation associated with this proposed definition with other existing ones.

West Nile virus (WNV) outbreaks in North America have been characterized by substantial die-offs of American crows (Corvus brachyrhynchos). In contrast, a low incidence of bird deaths has been observed during WNV epidemic activity in Europe. To examine the susceptibility of the western European counterpart of American crows, we inoculated carrion crows (Corvus corone) with WNV strains isolated in Greece (Gr-10), Italy (FIN and Ita09), and Hungary (578/10) and with the highly virulent North American genotype strain (NY99). We also inoculated American crows with a selection of these strains to examine the strains' virulence in a highly susceptible bird species. Infection with all strains, except WNV FIN, resulted in high rates of death and high-level viremia in both bird species and virus dissemination to several organs. These results suggest that carrion crows are highly susceptible to WNV and may potentially be useful as part of dead bird surveillance for early warning of WNV activity in Europe.

Abstract This article presents a review of research findings that investigate women's use of violence in intimate relationships, as well as the phenomena of increased arrests of women in domestic violence disputes. A brief outline of the extant national/regional data concerning the use of intimate partner violence (IPV) by men and women is presented. This is followed by a review of findings from data collected on smaller samples concerning differences between male and female IPV and genderized reactions, most notably to the differential physical, psychological, and emotional impact of IPV. Measurement methods that impact these national, regional, and local findings are discussed, followed by a review of what little is known about female arrests and "dual battering." An integration of the literature shows that a mere "count" of IPV by gender de-contextualizes and obscures the negative effects of violence against women, women's motivations for using IPV, and the meaning of recent increased arrests of women who resort to IPV.