Efficient CPP-mediated Cre protein delivery to developing and adult CNS tissues

<p>Abstract</p> <p>Background</p> <p>Understanding and manipulating gene function in physiological conditions is a major objective for both fundamental and applied research. In contrast to other experimental settings, which use either purely genetic or gene delivery (viral or non-viral) strategies, we report here a strategy based on direct protein delivery to central nervous system (CNS) tissues. We fused Cre recombinase with cell-penetrating peptides and analyzed the intracellular biological activity of the resulting chimerical proteins when delivered into cells endowed with Cre-mediated reporter gene expression.</p> <p>Results</p> <p>We show that active Cre enzymatic conjugates are readily internalized and exert their enzymatic activity in the nucleus of adherent cultured cells. We then evaluated this strategy in organotypic cultures of neural tissue explants derived from reporter mice carrying reporter "floxed" alleles. The efficacy of two protocols was compared on explants, either by direct addition of an overlying drop of protein conjugate or by implantation of conjugate-coated beads. In both cases, delivery of Cre recombinase resulted in genomic recombination that, with the bead protocol, was restricted to discrete areas of embryonic and adult neural tissues. Furthermore, delivery to adult brain tissue resulted in the transduction of mature postmitotic populations of neurons.</p> <p>Conclusion</p> <p>We provide tools for the spatially restricted genetic modification of cells in explant culture. This strategy allows to study lineage, migration, differentiation and death of neural cells. As a proof-of-concept applied to CNS tissue, direct delivery of Cre recombinase enabled the selective elimination of an interneuron subpopulation of the spinal cord, thereby providing a model to study early events of neurodegenerative processes. Thus our work opens new perspectives for both fundamental and applied cell targeting protocols using proteic cargoes which need to retain full bioactivity upon internalisation, as illustrated here with the oligomeric Cre recombinase.</p

Temporally coherent mesh sequence segmentations

In this report, we consider the problem of fully automatic segmentation of mesh sequences, with or without temporal coherence. More precisely, our goal is to identify model parts that consistently move rigidly over time. We propose a novel framework that incrementally adapts segments along a sequence based on the coherence of motion information within each segment. In contrast to existing approaches, this framework handles meshes independently reconstructed at each time instant, provided that motion cues are available. It allows therefore for meshes with varying connectivity as well as varying topology. Experiments on various data sets in addition to a quantitative evaluation demonstrate the effectiveness and robustness of the approach.Nous considérons dans ce rapport le problème de la segmentation entièrement automatique de séquences de maillages, avec ou sans cohérence temporelle. Plus précisément, notre but est d'identifier les parties d'un modèle qui se déplacent rigidement de manière cohérente au cours du temps. Nous proposons un canevas nouveau pour adapter ces régions de manière incrémentale le long de la séquence, en se basant sur la cohérence de l'information de mouvement dans chaque région. Contrairement aux approches existantes, ce canevas permet de traiter les séquences de maillages reconstruits indépendamment à chaque pas de temps, pourvu que des indicateurs de mouvement soient disponibles. Il permet donc de segmenter des maillages avec changement de connectivité et/ou changement de topologie. Des expériences sur plusieurs jeux de données ainsi qu'une évaluation quantitative démontrent l'efficacité ainsi que la robustesse de cette approche

Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa

BACKGROUND: Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI). We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa. METHODS: We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosa monomicrobial nBSI. RESULTS: The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiologic Score (SAPS II), were calculated daily from 2 days prior through 2 days after the first positive blood culture. Calculation of the area under the receiver operating characteristic (ROC) curve confirmed that APACHE II and SAPS II at day -1 and SOFA at day +1 were better predictors of outcome than days -2, 0 and day 2 of BSI. By stepwise logistic regression analysis of these three scoring systems, SAPS II (OR: 13.03, CI95% 2.51–70.49) and APACHE II (OR: 12.51, CI95% 3.12–50.09) on day -1 were the best predictors for mortality. CONCLUSION: SAPS II and APACHE II are more accurate than the SOFA score for predicting mortality in this group of patients at day -1 of BSI

Histoire chronologique de Quentovic et d'Étaples, par G. Souquet.

Dupont Edmond. Histoire chronologique de Quentovic et d'Étaples, par G. Souquet.. In: Bibliothèque de l'école des chartes. 1864, tome 25. pp. 471-473

The identification of terrains for mobile robots using eigenspace and neural network methods

Today’s autonomous vehicles operate within an increasingly larger set of environments compared to earlier research in which environments were more controlled. In particular, unmanned ground vehicles (UGV’s) must be able to travel on whatever terrain the mission offers, including sand, mud, or even snow. These terrains can affect the performance and controllability of the vehicle. Like a human driver who feels his vehicle’s response to the terrain and takes appropriate steps to compensate, a UGV that can autonomously perceive its terrain can also make necessary changes to its control strategy. This article focuses on the development of a terrain detection algorithm based on features extracted from terrain induced vehicle vibration. Research is conducted to reduce correlation of traversing terrains at different speeds. Procedures are presented to remove the dependencies of speed through eigendecompositon methods and applying the probabilistic neural network for classification between nonlinear boundaries. Experimental results based on iRobot’s ATRV Jr demonstrate that the algorithm is able to identify multi-differentiated terrains broadly defined as grass, asphalt, and gravel

Dynamical response and dimensional crossover for spatially anisotropic antiferromagnets

Theoretically challenging, the understanding of the dynamical response in quantum antiferromagnets is of great interest, in particular for both inelastic neutron scattering (INS) and nuclear magnetic resonance (NMR) experiments. In such a context, we theoretically address this question for quasi-one-dimensional quantum magnets, e.g. weakly coupled spin chains for which many compounds are available in Nature. In this class of systems, the dimensional crossover between a three-dimensional ordered regime at low temperature towards one-dimensional physics at higher temperature is a non-trivial issue, notably difficult concerning dynamical properties. Here we present a comprehensive theoretical study based on both analytical calculations (bosonization + random phase and self-consistent harmonic approximations) and numerical simulations (quantum Monte Carlo + stochastic analytic continuation) which allows us to describe the full temperature crossover for the NMR relaxation rate $1/T_1$, from one-dimensional Tomonaga-Luttinger liquid physics to the three-dimensional ordered regime, as a function of inter-chain couplings. The dynamical structure factor, directly probing the INS intensity, is also computed in the different regimes

Dynamical response and dimensional crossover for spatially anisotropic antiferromagnets

International audienc

[1 lettre d'Edmond Dupont à Charles Nuitter, 6 novembre 1874] (manuscrit autographe)

Papier à en-tête des Archives Nationales. - L'informe qu'un grand nombre de liasses sont à sa disposition avant de réintégrer le dépô

Temporally coherent mesh sequence segmentations

In this report, we consider the problem of fully automatic segmentation of mesh sequences, with or without temporal coherence. More precisely, our goal is to identify model parts that consistently move rigidly over time. We propose a novel framework that incrementally adapts segments along a sequence based on the coherence of motion information within each segment. In contrast to existing approaches, this framework handles meshes independently reconstructed at each time instant, provided that motion cues are available. It allows therefore for meshes with varying connectivity as well as varying topology. Experiments on various data sets in addition to a quantitative evaluation demonstrate the effectiveness and robustness of the approach.Nous considérons dans ce rapport le problème de la segmentation entièrement automatique de séquences de maillages, avec ou sans cohérence temporelle. Plus précisément, notre but est d'identifier les parties d'un modèle qui se déplacent rigidement de manière cohérente au cours du temps. Nous proposons un canevas nouveau pour adapter ces régions de manière incrémentale le long de la séquence, en se basant sur la cohérence de l'information de mouvement dans chaque région. Contrairement aux approches existantes, ce canevas permet de traiter les séquences de maillages reconstruits indépendamment à chaque pas de temps, pourvu que des indicateurs de mouvement soient disponibles. Il permet donc de segmenter des maillages avec changement de connectivité et/ou changement de topologie. Des expériences sur plusieurs jeux de données ainsi qu'une évaluation quantitative démontrent l'efficacité ainsi que la robustesse de cette approche