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Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human beta-globin locus
No full textInternational audienceNaturally occurring, large deletions in the beta-globin locus result in hereditary persistence of fetal hemoglobin, a condition that mitigates the clinical severity of sickle cell disease (SCD) and beta-thalassemia. We designed a clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) strategy to disrupt a 13.6-kb genomic region encompassing the delta- and beta-globin genes and a putative gamma-delta intergenic fetal hemoglobin (HbF) silencer. Disruption of just the putative HbF silencer results in a mild increase in gamma-globin expression, whereas deletion or inversion of a 13.6-kb region causes a robust reactivation of HbF synthesis in adult erythroblasts that is associated with epigenetic modifications and changes in chromatin contacts within the beta-globin locus. In primary SCD patient-derived hematopoietic stem/progenitor cells, targeting the 13.6-kb region results in a high proportion of gamma-globin expression in erythroblasts, increased HbF synthesis, and amelioration of the sickling cell phenotype. Overall, this study provides clues for a potential CRISPR/Cas9 genome editing approach to the therapy of beta-hemoglobinopathies
Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation
No full textInternational audience=Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors
Impact of the face registration techniques on facial expressions recognition
No full textInternational audienceRecent methodologies for facial expression recognition have been proposed and have obtained good results in near-frontal view. However, these situations do not fairly represent in-the-wild challenges, where expressions are natural and the subject is free of its movement. This is reflected in the accuracy drop of facial expression methods obtained on recent databases. Two challenges (head pose variations and large displacements) in facial expression recognition are studied in this paper. Experiments are proposed in order to quantify the impact of free head movements using representative expression recognition approaches (LBP, LBP-TOP, HOOF). We propose an experimental protocol (SNaP-2DFe) that records, under controlled light, facial expressions with two cameras: one attached on the head and one placed in front of the subject. As in both cameras facial expressions are the same, differences in performances measured on each camera show the impact of head pose variations and large displacements on the underlying recognition approach
An Agent-based Distributed Approach for Bike Sharing Systems
No full textInternational audienceShared bikes are wildly welcomed and becoming increasing popular in the world, as a result, quite a few bike sharing systems have been conducted to provide services for bike users. However, current bike sharing systems are not flexible and considerate enough for public bike users because of the fixed stations and not well emphasized about user's satisfactions. In this paper, an agent-based distributed approach for bike sharing systems is proposed, this approach aims at helping users obtain a needed shared bike successfully and efficiently. We pay more attention on user's preferences to improve the satisfaction to the target shared bike, meanwhile, trust and probability are considered to improve the efficiency and success rate. To the end, results from simulation studies demonstrate the effectiveness of our proposed method
Les submorphémies fantômes. Fausses coupes, liaisons dangereuses et autres réanalyses submorphémiquement motivées en espagnol et en français
No full textInternational audienceS’appuyant sur une redéfinition du signifiant et de la parole en tant qu’actions corporelles, cette étude part de l’idée qu’un processus vocal est organisé à l’interprétation par une analyse spontanée consistant notamment à produire des dégroupements et regroupements de segments appelés « signifiants ». On étudie ici des phénomènes de déviance dans la segmentation et la frontérisation des signifiants relativement à la prescription académique (dégroupements et regroupements non conventionnels, liaisons non entérinées par la norme). On s’intéresse à la possible efficacité de ces déviances en tant qu’actes motivés d’analyse spontanée, et à la pertinence potentielle de segments que font surgir ces (ré)analyses : à savoir, des segments « fantômes » se superposant à ou s’interposant entre ceux qu’attendrait une analyse conventionnelle, et dont la pertinence pourra dépendre notamment de leur inscription dans des réseaux signifiants de niveau morphémique ou sub-morphémique. Dans le cadre du deuxième volume de Signifiances invitant à s’interroger sur la diabolicité du symbole et la « duplicité du signe », notre propos est ainsi d’observer la façon dont, derrière la fixité apparente d’un signifiant symbolique (réifié en entité stabilisée, engoncé dans une forme délimitée par des frontières), peut se cacher un signifiant dia-bolique, issu d’un processus d’analyse et de construction, reconstruction, réassemblage à géométrie variable
Multi-Disciplinary Design Multi-Objective Optimization of Aerospace Vehicles using Surrogate Models
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French publishing attitudes in the open access era: The case of mathematics, biology, and computer science
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Assessing primitives performance on multi-stage execution
No full textInternational audienceVirtual machines, besides the interpreter and just-in-time compiler optimization facilities, also include a set of primitive operations that the client language can use. Some of these are essential and cannot be performed in any other way. Others are optional: they can be expressed in the client language but are often implemented in the virtual machine to improve performance when the just-in-time compiler is unable to do so (start-up performance, speculative optimizations not implemented or not mature enough, etc.). In a hybrid runtime, where code is executed by an interpreter and a just-in-time compiler, the implementor can choose to implement optional primitives in the client language , in the virtual machine implementation language (typically C or C++), or on top of the just-in-time compiler back-end. This raises the question of the maintenance and performance trade-offs of the different alternatives. As a case study, we implemented the String comparison optional primitive in each case. This paper describes the different implementations , discusses the maintenance cost of each of them and evaluates for different string sizes the execution time in Cog, a Smalltalk virtual machine
Préambule. La « Disputa de los Griegos y de los Romanos » (Libro de buen amor) : interlocution, geste, signe linguistique
No full textInternational audienceDans le cadre du 2e volume de Signifiances, ce préambule propose de poser les termes du débat à partir d’une « fable exemplaire » : la « Dispute des Grecs et des Romains », quelques strophes d’une œuvre en vers du xive siècle parmi les plus célèbres de la littérature espagnole, le Libro de Buen Amor. Ce célèbre épisode s’avère être une parfaite illustration de quelques grands principes linguistiques, pourtant peu mobilisés dans l’analyse traditionnelle : la « double contingence » ou l’ignorance par chacun des interlocuteurs de ce que le signe signifie pour l’autre ; le signifié comme construit ex post, résultant du positionnement d’un observateur extérieur ; la double conception du signe, comme représentation et comme action incarnée. L’analyse de cet édifiant passage débouche sur une évocation des différentes formes que prend la duplicité du signe linguistique