Fluctuations of Rare Event Simulation with Monte Carlo Splitting in the Small Noise Asymptotics

Diffusion processes with small noise conditioned to reach a target set are considered. The AMS algorithm is a Monte Carlo method that is used to sample such rare events by iteratively simulating clones of the process and selecting trajectories that have reached the highest value of a so-called importance function. In this paper, the large sample size relative variance of the AMS small probability estimator is considered. The main result is a large deviations logarithmic equivalent of the latter in the small noise asymptotics, which is rigorously derived. It is given as a maximisation problem explicit in terms of the quasi-potential cost function associated with the underlying small noise large deviations. Necessary and sufficient geometric conditions ensuring the vanishing of the obtained quantity ('weak' asymptotic efficiency) are provided. Interpretations and practical consequences are discussed

Smart: on the internets

This article is based on three different researches. The first one is published in the book entitled Mainstream, and it is an observation of the cultural changes in the age of globalization. The second one relates the identity and gender issues, and the gay culture, observing the impacts of the globalization on the identity process. The third and more recently released research is Smart: on the internets, which reports the fast globalization process and its effects on the Internet. This research was performed in 50 different countries and presents the concept of smart curation.A pesquisa apresentada se baseia em três diferentes pesquisas. A primeira delas está publicada em português, numa obra intitulada Mainstream, e trata da cultura na era da mundialização. A segunda pesquisa destaca as questões da identidade, do gênero e da causa gay. Nela, é observado como esse processo de identificação se transforma a partir da mundialização. A terceira pesquisa, publicada em português em novembro de 2015, chama-se Smart: o que você não sabe sobre a internet e refere-se à internet e ao processo de mundialização acelerado. Smart é uma pesquisa realizada em 50 diferentes países e apresenta o conceito de curadoria smart.

(Post-)queer citizenship in contemporary republican France

1996 saw the publication of Frédéric Martel’s Le Rose et le noir, a comprehensive study of three decades of gay life in metropolitan France. The predominantly anti-communitarian stance adopted by Martel in the epilogue to the first edition of his work had evolved, by the time of the book’s publication en poche in 2000, into a more nuanced view of the interactions and intersections between queer and republican identities in contemporary France. This development was influenced, in large part, by concrete changes which took place over the second half of the 1990s, centring around the introduction of the PACS in 1999, and leading to an ever-broadening debate. This paper will begin by setting forth the ways in which Martel’s position changed and analysing the attitudinal, social, and legislative backdrop which paved the way for such a change to occur. It will then bring Martel’s work into a dialogue with the writings of Eric Fassin and Maxime Foerster, both of whom have, like Martel, offered crucial analyses of the place of queer citizens within the contemporary French republic. Particular attention will first be paid to the ways in which Fassin, in his writings, has underlined the salience of the ‘droit du sol/droit du sang’ debate, traditionally associated with questions of ethnic belonging, in light of public and political discussions revolving around questions of queer kinship raised by the introduction of the PACS. This will lead into an examination of Foerster’s assertion that gay citizens of the Republic, in the era of the PACS, find themselves in a role previously held by women, in other words, as elements that require integration within a republican model. Foerster argues that this requirement to integrate is indicative of the fact that the traditional republican claim that the citizen is a blank canvas is at best misguided, and, at worst, has been deliberately subverted. This paper will examine the manner in which Martel and Fassin’s observations can be used to further strengthen the points raised by Foerster, concluding with the latter that a true engagement with the issues raised by debates around queer citizenship over the past decade can, in fact, allow the contemporary republican citizen to ‘devenir ceux [qu’il] est’. In other words, the article will conclude that the potential impact of the PACS legislation and the broader discussions it has provoked could be a renegotiation of the relationship between queer citizens and the republic

Abnormal insulin-like growth factor 1 signaling in human osteoarthritic subchondral bone osteoblasts

Insulin-like growth factor (IGF)-1 is a key factor in bone homeostasis and could be involved in bone tissue sclerosis as observed in osteoarthritis (OA). Here, we compare the key signaling pathways triggered in response to IGF-1 stimulation between normal and OA osteoblasts (Obs). Primary Obs were prepared from the subchondral bone of tibial plateaus of OA patients undergoing knee replacement or from normal individuals at autopsy. Phenotypic characterization of Obs was evaluated with alkaline phosphatase and osteocalcin release. The effect of IGF-1 on cell proliferation, alkaline phosphatase and collagen synthesis was evaluated in the presence or not of 50 ng/ml IGF-1, whereas signaling was studied with proteins separated by SDS-PAGE before western blot analysis. We also used immunoprecipitation followed by western blot analysis to detect interactions between key IGF-1 signaling elements. IGF-1 receptor (IGF-1R), Shc, Grb2, insulin receptor substrate (IRS)-1, and p42/44 mitogen-activated protein kinase (MAPK) levels were similar in normal and OA Obs in the presence or absence of IGF-1. After IGF-1 stimulation, the phosphorylation of IGF-1R in normal and OA Obs was similar; however, the phosphorylation of IRS-1 was reduced in OA Ob. In addition, the PI3K pathway was activated similarly in normal and OA Obs while that for p42/44 MAPK was higher in OA Obs compared to normal. p42/44 MAPK can be triggered via an IRS-1/Syp or Grb2/Shc interaction. Interestingly, Syp was poorly phosphorylated under basal conditions in normal Obs and was rapidly phosphorylated upon IGF-1 stimulation, yet Syp showed a poor interaction with IRS-1. In contrast, Syp was highly phosphorylated in OA Obs and its interaction with IRS-1 was very strong initially, yet rapidly dropped with IGF-1 treatments. The interaction of Grb2 with IRS-1 progressively increased in response to IGF-1 in OA Obs whereas this was absent in normal Ob. IGF-1 stimulation altered alkaline phosphatase in Ob, an effect reduced in the presence of PD98059, an inhibitor of p42/44 MAPK signaling, whereas neither IGF-1 nor PD98059 had any significant effect on collagen synthesis. In contrast, cell proliferation was higher in OA Obs compared to normal under basal conditions, and IGF-1 stimulated more cell proliferation in OA Obs than in normal Ob, an effect totally dependent on p42/44 MAPK activiy. The altered response of OA Obs to IGF-1 may be due to abnormal IGF-1 signaling in these cells. This is mostly linked with abnormal IRS-1/Syp and IRS-1/Grb2 interaction in these cells

A review of intrinsic optical imaging serial blockface histology (ICI-SBH) for whole rodent brain imaging

In recent years, multiple serial histology techniques were developed to enable whole rodent brain imaging in 3-D. The main driving forces behind the emergence of these imaging techniques were the genome-wide atlas of gene expression in the mouse brain, the pursuit of the mouse brain connectome, and the BigBrain project. These projects rely on the use of optical imaging to target neuronal structures with histological stains or fluorescent dyes that are either expressed by transgenic mice or injected at specific locations in the brain. Efforts to adapt the serial histology acquisition scheme to use intrinsic contrast imaging (ICI) were also put forward, thus leveraging the natural contrast of neuronal tissue. This review focuses on these efforts. First, the origin of optical contrast in brain tissue is discussed with emphasis on the various imaging modalities exploiting these contrast mechanisms. Serial blockface histology (SBH) systems using ICI modalities are then reported, followed by a review of some of their applications. These include validation studies and the creation of multimodal brain atlases at a micrometer resolution. The paper concludes with a perspective of future developments, calling for a consolidation of the SBH research and development efforts around the world. The goal would be to offer the neuroscience community a single standardized open-source SBH solution, including optical design, acquisition automation, reconstruction algorithms, and analysis pipelines

Spectroscopy on Black Phosphorus exfoliated down to the monolayer

International audienc

Phase contrast reflectance confocal brain imaging at 1650 nm

ABSTRACT: Significance The imaging depth of microscopy techniques is limited by the ability of light to penetrate biological tissue. Recent research has addressed this limitation by combining a reflectance confocal microscope with the NIR-II (or shortwave infrared) spectrum. This approach offers significant imaging depth, is straightforward in design, and remains cost-effective. However, the imaging system, which relies on intrinsic signals, could benefit from adjustments in its optical design and post-processing methods to differentiate cortical cells, such as neurons and small blood vessels. Aim We implemented a phase contrast detection scheme to a reflectance confocal microscope using NIR-II spectral range as illumination. Approach We analyzed the features retrieved in the images while testing the imaging depth. Moreover, we introduce an acquisition method for distinguishing dynamic signals from the background, allowing the creation of vascular maps similar to those produced by optical coherence tomography. Results The phase contrast implementation is successful to retrieve deep images in the cortex up to 800μm using a cranial window. Vascular maps were retrieved at similar cortical depth and the possibility of combining multiple images can provide a vessel network. Conclusions Phase contrast reflectance confocal microscopy can improve the outlining of cortical cell bodies. With the presented framework, angiograms can be retrieved from the dynamic signal in the biological tissue. Our work presents an optical implementation and analysis techniques from a former microscope design

(Eta6-arene) ruthenium(II) complexes and metallo-papain hybrid as Lewis acid catalysts of Diels-Alder reaction in water.

International audienceCovalent embedding of a (eta(6)-arene) ruthenium(II) complex into the protein papain gives rise to a metalloenzyme displaying a catalytic efficiency for a Lewis acid-mediated catalysed Diels-Alder reaction enhanced by two orders of magnitude in water

Heterogeneous reconstruction of deformable atomic models in Cryo-EM

Cryogenic electron microscopy (cryo-EM) provides a unique opportunity to study the structural heterogeneity of biomolecules. Being able to explain this heterogeneity with atomic models would help our understanding of their functional mechanisms but the size and ruggedness of the structural space (the space of atomic 3D cartesian coordinates) presents an immense challenge. Here, we describe a heterogeneous reconstruction method based on an atomistic representation whose deformation is reduced to a handful of collective motions through normal mode analysis. Our implementation uses an autoencoder. The encoder jointly estimates the amplitude of motion along the normal modes and the 2D shift between the center of the image and the center of the molecule . The physics-based decoder aggregates a representation of the heterogeneity readily interpretable at the atomic level. We illustrate our method on 3 synthetic datasets corresponding to different distributions along a simulated trajectory of adenylate kinase transitioning from its open to its closed structures. We show for each distribution that our approach is able to recapitulate the intermediate atomic models with atomic-level accuracy.Comment: 8 pages, 1 figur

Fully automated dual-resolution serial optical coherence tomography aimed at diffusion MRI validation in whole mouse brains

An automated dual-resolution serial optical coherence tomography (2R-SOCT) scanner is developed. The serial histology system combines a low-resolution ( 25 mu m / voxel ) 3 x OCT with a high-resolution ( 1.5 mu m / voxel ) 40 x OCT to acquire whole mouse brains at low resolution and to target specific regions of interest (ROIs) at high resolution. The 40 x ROIs positions are selected either manually by the microscope operator or using an automated ROI positioning selection algorithm. Additionally, a multimodal and multiresolution registration pipeline is developed in order to align the 2R-SOCT data onto diffusion MRI (dMRI) data acquired in the same ex vivo mouse brains prior to automated histology. Using this imaging system, 3 whole mouse brains are imaged, and 250 high-resolution 40 x three-dimensional ROIs are acquired. The capability of this system to perform multimodal imaging studies is demonstrated by labeling the ROIs using a mouse brain atlas and by categorizing the ROIs based on their associated dMRI measures. This reveals a good correspondence of the tissue microstructure imaged by the high-resolution OCT with various dMRI measures such as fractional anisotropy, number of fiber orientations, apparent fiber density, orientation dispersion, and intracellular volume fraction