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Yang J.,Australian National University | Li H.,ANU | Dai Y.,CECS | Tan R.T.,National University of Singapore
Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition | Year: 2016

This paper deals with a challenging, frequently encountered, yet not properly investigated problem in two-frame optical flow estimation. That is, the input frames are compounds of two imaging layers - one desired background layer of the scene, and one distracting, possibly moving layer due to transparency or reflection. In this situation, the conventional brightness constancy constraint - the cornerstone of most existing optical flow methods - will no longer be valid. In this paper, we propose a robust solution to this problem. The proposed method performs both optical flow estimation, and image layer separation. It exploits a generalized double-layer brightness consistency constraint connecting these two tasks, and utilizes the priors for both of them. Experiments on both synthetic data and real images have confirmed the efficacy of the proposed method. To the best of our knowledge, this is the first attempt towards handling generic optical flow fields of two-frame images containing transparency or reflection.

Feyeux M.,French Institute of Health and Medical Research | Bourgois-Rocha F.,French Institute of Health and Medical Research | Redfern A.,University of Cardiff | Giles P.,University of Cardiff | And 12 more authors.
Human Molecular Genetics | Year: 2012

Huntington's disease (HD) is characterized by a late clinical onset despite ubiquitous expression of the mutant gene at all developmental stages. How mutant huntingtin impacts on signalling pathways in the pre-symptomatic period has remained essentially unexplored in humans due to a lack of appropriate models. Using multiple human embryonic stem cell lines derived from blastocysts diagnosed as carrying the mutant huntingtin gene by pre-implantation genetic diagnosis, we explored early developmental changes in gene expression using differential transcriptomics, combined with gain and loss of function strategies. We demonstrated a down-regulation of the HTT gene itself in HD neural cells and identified three genes, the expression of which differs significantly in HD cells when compared with wild-type controls, namely CHCHD2, TRIM4 and PKIB. Similar dysregulation had been observed previously for CHCDH2 and TRIM4 in blood cells from patients. CHCHD2 is involved in mitochondrial function and PKIB in protein kinase A-dependent pathway regulation, which suggests that these functions may be precociously impacted in HD. © The Author 2012. Published by Oxford University Press. All rights reserved.

Charbord J.,French Institute of Health and Medical Research | Poydenot P.,CECS | Bonnefond C.,CECS | Feyeux M.,French Institute of Health and Medical Research | And 14 more authors.
Stem Cells | Year: 2013

Decreased expression of neuronal genes such as brain-derived neurotrophic factor (BDNF) is associated with several neurological disorders. One molecular mechanism associated with Huntington disease (HD) is a discrete increase in the nuclear activity of the transcriptional repressor REST/NRSF binding to repressor element-1 (RE1) sequences. High-throughput screening of a library of 6,984 compounds with luciferase-assay measuring REST activity in neural derivatives of human embryonic stem cells led to identify two benzoimidazole-5-carboxamide derivatives that inhibited REST silencing in a RE1-dependent manner. The most potent compound, X5050, targeted REST degradation, but neither REST expression, RNA splicing nor binding to RE1 sequence. Differential transcriptomic analysis revealed the upregulation of neuronal genes targeted by REST in wild-type neural cells treated with X5050. This activity was confirmed in neural cells produced from human induced pluripotent stem cells derived from a HD patient. Acute intraventricular delivery of X5050 increased the expressions of BDNF and several other REST-regulated genes in the prefrontal cortex of mice with quinolinate-induced striatal lesions. This study demonstrates that the use of pluripotent stem cell derivatives can represent a crucial step toward the identification of pharmacological compounds with therapeutic potential in neurological affections involving decreased expression of neuronal genes associated to increased REST activity, such as Huntington disease. Stem Cells 2013;31:1816-1828 © AlphaMed Press.

Zhang D.,CECS | He X.,NICTA | Li H.,NICTA
2014 International Conference on Digital Image Computing: Techniques and Applications, DICTA 2014 | Year: 2015

We present a street scene layout estimation method based on transferring layout annotation from a (large) image database and its application for distant object detection. Inspired by nonparametric scene labeling approaches, we estimate a scene's geometric layout by matching global image descriptors and retrieving the most similar layout configuration. Our label transfer is done for each sub-region of an image and a tiered scene model is used to integrate all the local label information into a coherent scene layout prediction. Given the geometric layout, we use a super-resolution method to zoom in the distance region and refine the search in object detection. On KITTI dataset, we show that we can reliably generate scene layout and improve the detection of distant cars over the state of the art DPM detector. © 2014 IEEE.

Maury Y.,CECS | Gauthier M.,French Institute of Health and Medical Research | Peschanski M.,CECS | Peschanski M.,French Institute of Health and Medical Research | Martinat C.,French Institute of Health and Medical Research
BioEssays | Year: 2012

Considerable hope surrounds the use of disease-specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease-specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic-like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding a larger number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease-specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease-specific human pluripotent stem cells for drug screening. © 2012 WILEY Periodicals, Inc.

Nissan X.,CECS | Blondel S.,French Institute of Health and Medical Research | Peschanski M.,French Institute of Health and Medical Research
Biochemical Society Transactions | Year: 2011

Progeria, also known as HGPS (Hutchinson-Gilford progeria syndrome), is a rare fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (C1804T) of the gene encoding lamins A and C, LMNA, leading to the production of a truncated form of the protein called progerin. Owing to their unique potential to self-renew and to differentiate into any cell types of the organism, pluripotent stem cells offer a unique tool to studymolecular and cellular mechanisms related to this global and systemic disease. Recent studies have exploited this potential by generating human induced pluripotent stem cells from HGPS patients' fibroblasts displaying several phenotypic defects characteristic of HGPS such as nuclear abnormalities, progerin expression, altered DNA-repair mechanisms and premature senescence. Altogether, these findings provide new insights on the use of pluripotent stem cells for pathological modelling and may open original therapeutic perspectives for diseases that lack pre-clinical in vitro human models, such as HGPS. ©The Authors Journal compilation ©2011 Biochemical Society.

Onteniente B.,French Institute of Health and Medical Research | Polentes J.,CECS
Cerebrovascular Diseases | Year: 2011

With the development of stem cell (SC) biology, cell-based therapy has become a highly challenging field for experimental and clinical research. Among neurological disorders, stroke has pioneered the clinical application of SC. Safety concerns have prevailed for pilot clinical studies and important preclinical work is ongoing to help SC therapy reach the level of generalization. Stroke is classically divided into an acute, a subacute and a chronic phase. Each phase is defined by a complex array of events with overlapping and distinct kinetics that lead to both rapid tissue degeneration and long-lasting remodeling. Each SC type possesses intrinsic properties - transposed via cell-autonomous and non-cell-autonomous signaling - that would more specifically address some of these events. A better definition of what is expected from SC therapy in stroke might help assign SC sources to the acute or chronic phases and possibly optimize their use in the clinic. Copyright © 2011 S. Karger AG, Basel.

Giraud-Triboult K.,CECS | Rochon-Beaucourt C.,French Institute of Health and Medical Research | Nissan X.,CECS | Champon B.,CECS | And 2 more authors.
Physiological Genomics | Year: 2011

Mesenchymal stem cells (MSCs) are present in a wide variety of tissues during development of the human embryo starting as early as the first trimester. Gene expression profiling of these cells has focused primarily on the molecular signs characterizing their potential heterogeneity and their differentiation potential. In contrast, molecular mechanisms participating in the emergence of MSC identity in embryo are still poorly understood. In this study, human embryonic stem cells (hESs) were differentiated toward MSCs (ES-MSCs) to compare the genetic patterns between pluripotent hESs and multipotent MSCs by a large genomewide expression profiling of mRNAs and microRNAs (miRNAs). After whole genome differential transcriptomic analysis, a stringent protocol was used to search for genes differentially expressed between hESs and ES-MSCs, followed by several validation steps to identify the genes most specifically linked to the MSC phenotype. A network was obtained that encompassed 74 genes in 13 interconnected transcriptional systems that are likely to contribute to MSC identity. Pairs of negatively correlated miRNAs and mRNAs, which suggest miRNA-target relationships, were then extracted and validation was sought with the use of Pre-miRs. We report here that underexpression of miR-148a and miR-20b in ES-MSCs, compared with ESs, allows an increase in expression of the EPAS1 (Endothelial PAS domain 1) transcription factor that results in the expression of markers of the MSC phenotype specification. Copyright © 2011 the American Physiological Society.

Nicoleau C.,French Institute of Health and Medical Research | Varela C.,CECS | Bonnefond C.,CECS | Maury Y.,CECS | And 6 more authors.
Stem Cells | Year: 2013

Wnt-ligands are among key morphogens that mediate patterning of the anterior territories of the developing brain in mammals. We qualified the role of Wnt-signals in regional specification and subregional organization of the human telencephalon using human pluripotent stem cells (hPSCs). One step neural conversion of hPSCs using SMAD inhibitors leads to progenitors with a default rostral identity. It provides an ideal biological substrate for investigating the role of Wnt signaling in both anteroposterior and dorso-ventral processes. Challenging hPSC-neural derivatives with Wnt-antagonists, alone or combined with sonic hedgehog (Shh), we found that Wnt-inhibition promote both telencephalic specification and ventral patterning of telencephalic neural precursors in a dose-dependent manner. Using optimal Wnt-antagonist and Shh-agonist signals we produced human ventral-telencephalic precursors, committed to differentiation into striatal projection neurons both in vitro and in vivo after homotypic transplantation in quinolinate-lesioned rats. This study indicates that sequentially organized Wnt-signals play a key role in the development of human ventral telencephalic territories from which the striatum arise. In addition, the optimized production of hPSC-derived striatal cells described here offers a relevant biological resource for exploring and curing Huntington disease. Stem Cells 2013;31:1763-1774 © AlphaMed Press.

Nedelec S.,CECS | Onteniente B.,French Institute of Health and Medical Research | Peschanski M.,CECS | Peschanski M.,French Institute of Health and Medical Research | Martinat C.,French Institute of Health and Medical Research
Current Gene Therapy | Year: 2013

The fundamental inaccessibility of the human neural cell types affected by neurological disorders prevents their isolation for in vitro studies of disease mechanisms or for drug screening efforts. Pluripotent stem cells represent a new interesting way to generate models of human neurological disorders, explore the physiopathological mechanisms and develop new therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induced pluripotent stem cells (hiPSCs) together with the continuous improvement of methods to differentiate these cells into disease-affected neuronal subtypes opens new perspectives to model and understand a large number of human pathologies. This review focuses on the opportunities concerning the use disease-specific human pluripotent stem cells as well as the different challenges that still need to be overcome. We also discuss the recent improvements in the genetic manipulation of human pluripotent stem cells and the consequences of these on disease modeling and drug screening for neurological diseases. © 2013 Bentham Science Publishers.

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