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Patent
Ecole Normale Superieure de Paris, French National Center for Scientific Research, University Pierre and Marie Curie | Date: 2016-10-26

The present invention relates to a method for the determination of a nucleic acid sequence by physical manipulation. In particular, the said method comprises the steps of denaturing a double-stranded nucleic acid molecule corresponding to the said nucleic acid sequence by applying a physical force to the said molecule; and detecting a blockage of the renaturation of the double-stranded nucleic acid molecule. More specifically, the method comprises the steps of denaturing a double-stranded nucleic acid molecule corresponding to the said nucleic acid sequence by applying a physical force to the said molecule; providing a single-stranded nucleic acid molecule; renaturing the said double stranded nucleic acid molecule in the presence of the said single-stranded nucleic acid molecule; and detecting a blockage of the renaturation of the double-stranded nucleic acid.


Patent
Ecole Normale Superieure de Paris, French National Center for Scientific Research, University Pierre and Marie Curie | Date: 2016-10-26

The present invention relates to a method for the determination of a nucleic acid sequence by physical manipulation. The method is based on the precise determination of the localization of the replicating fork on the template by measuring the physical distance between one end of the molecule and the fork. This allows the determination of the physical location of the site where a pause or a blockage of the replication occurs, and deducing therefrom information on the sequence of the nucleic acid.


Rooy M.,Ecole Normale Superieure de Paris
Nature Medicine | Year: 2017

The prefrontal cortex (PFC) underlies higher cognitive processes that are modulated by nicotinic acetylcholine receptor (nAChR) activation by cholinergic inputs. PFC spontaneous default activity is altered in neuropsychiatric disorders, including schizophrenia—a disorder that can be accompanied by heavy smoking. Recently, genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) in the human CHRNA5 gene, encoding the α5 nAChR subunit, that increase the risks for both smoking and schizophrenia. Mice with altered nAChR gene function exhibit PFC-dependent behavioral deficits, but it is unknown how the corresponding human polymorphisms alter the cellular and circuit mechanisms underlying behavior. Here we show that mice expressing a human α5 SNP exhibit neurocognitive behavioral deficits in social interaction and sensorimotor gating tasks. Two-photon calcium imaging in awake mouse models showed that nicotine can differentially influence PFC pyramidal cell activity by nAChR modulation of layer II/III hierarchical inhibitory circuits. In α5-SNP-expressing and α5-knockout mice, lower activity of vasoactive intestinal polypeptide (VIP) interneurons resulted in an increased somatostatin (SOM) interneuron inhibitory drive over layer II/III pyramidal neurons. The decreased activity observed in α5-SNP-expressing mice resembles the hypofrontality observed in patients with psychiatric disorders, including schizophrenia and addiction. Chronic nicotine administration reversed this hypofrontality, suggesting that administration of nicotine may represent a therapeutic strategy for the treatment of schizophrenia, and a physiological basis for the tendency of patients with schizophrenia to self-medicate by smoking. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Heard E.,French Institute of Health and Medical Research | Heard E.,Collège de France | Martienssen R.A.,Howard Hughes Medical Institute | Martienssen R.A.,Ecole Normale Superieure de Paris
Cell | Year: 2014

Since the human genome was sequenced, the term "epigenetics" is increasingly being associated with the hope that we are more than just the sum of our genes. Might what we eat, the air we breathe, or even the emotions we feel influence not only our genes but those of descendants? The environment can certainly influence gene expression and can lead to disease, but transgenerational consequences are another matter. Although the inheritance of epigenetic characters can certainly occur - particularly in plants - how much is due to the environment and the extent to which it happens in humans remain unclear. © 2014 Elsevier Inc.


Plougonven R.,Ecole Normale Superieure de Paris | Zhang F.,Pennsylvania State University
Reviews of Geophysics | Year: 2014

For several decades, jets and fronts have been known from observations to be significant sources of internal gravity waves in the atmosphere. Motivations to investigate these waves have included their impact on tropospheric convection, their contribution to local mixing and turbulence in the upper troposphere, their vertical propagation into the middle atmosphere, and the forcing of its global circulation. While many different studies have consistently highlighted jet exit regions as a favored locus for intense gravity waves, the mechanisms responsible for their emission had long remained elusive: one reason is the complexity of the environment in which the waves appear; another reason is that the waves constitute small deviations from the balanced dynamics of the flow generating them; i.e., they arise beyond our fundamental understanding of jets and fronts based on approximations that filter out gravity waves. Over the past two decades, the pressing need for improving parameterizations of nonorographic gravity waves in climate models that include a stratosphere has stimulated renewed investigations. The purpose of this review is to present current knowledge and understanding on gravity waves near jets and fronts from observations, theory, and modeling, and to discuss challenges for progress in coming years. © 2013. American Geophysical Union. All Rights Reserved.


Corson F.,Ecole Normale Superieure de Paris
Physical Review Letters | Year: 2010

The structure of networks that provide optimal transport properties has been investigated in a variety of contexts. While many different formulations of this problem have been considered, it is recurrently found that optimal networks are trees. It is shown here that this result is contingent on the assumption of a stationary flow through the network. When time variations or fluctuations are allowed for, a different class of optimal structures is found, which share the hierarchical organization of trees yet contain loops. The transitions between different network topologies as the parameters of the problem vary are examined. These results may have strong implications for the structure and formation of natural networks, as is illustrated by the example of leaf venation networks. © 2010 The American Physical Society.


Felix M.-A.,Ecole Normale Superieure de Paris
Current Opinion in Genetics and Development | Year: 2012

Developmental systems can produce a variety of patterns and morphologies when the molecular and cellular activities within them are varied. With the advent of quantitative modeling, the range of phenotypic output of a developmental system can be assessed by exploring model parameter space. Here I review recent examples where developmental evolution is studied using quantitative models, which increasingly rely on empirically determined molecular signaling pathways and their crosstalk. Quantitative pathway evolution may result in dramatic morphological changes. Alternatively, in many developmental systems, the phenotypic output is robust to a range of parameter variation, and cryptic developmental evolution may occur without morphological change. Formalization and measurements of the relationship between genetic variation and parameter variation in developmental models remain in their infancy. © 2012 Elsevier Ltd.


Balibar S.,Ecole Normale Superieure de Paris
Nature | Year: 2010

A 'supersolid' is a quantum solid in which a fraction of the mass is superfluid. As a remarkable consequence, it is rigid, but part of its mass is able to flow owing to quantum physical processes. This paradoxical state of matter was considered as a theoretical possibility as early as 1969, but its existence was discovered only in 2004, in 4 He. Since then, intense experimental and theoretical efforts have been made to explain the origins of this exotic state of matter. It now seems that its physical interpretation is more complicated than originally thought. © 2010 Macmillan Publishers Limited. All rights reserved.


Bach F.,Ecole Normale Superieure de Paris
Foundations and Trends in Machine Learning | Year: 2013

Submodular functions are relevant to machine learning for at least two reasons: (1) some problems may be expressed directly as the optimization of submodular functions and (2) the Lovasz extension of submodular functions provides a useful set of regularization functions for supervised and unsupervised learning. In this monograph, we present the theory of submodular functions from a convex analysis perspective, presenting tight links between certain polyhedra, combinatorial optimization and convex optimization problems. In particular, we show how submodular function minimization is equivalent to solving a wide variety of convex optimization problems. This allows the derivation of new efficient algorithms for approximate and exact submodular function minimization with theoretical guarantees and good practical performance. By listing many examples of submodular functions, we review various applications to machine learning, such as clustering, experimental design, sensor placement, graphical model structure learning or subset selection, as well as a family of structured sparsity-inducing norms that can be derived and used from submodular functions. © 2013 F. Bach.


Ramus F.,Ecole Normale Superieure de Paris
Trends in Cognitive Sciences | Year: 2014

A new study reports that activations of superior temporal regions for speech are normal in dyslexia, although being less well connected to downstream frontal regions. These findings support the hypothesis of a deficit in the access to phonological representations rather than in the representations themselves. © 2014 Elsevier Ltd.

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