LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Figure, figuration (du rêve à la peinture)

[Résumé en français]Il s'agit de rechercher quelle place pourraient prendre, dans le champ lacanien, les processus de figuration du rêve mis en évidence par Freud. La définition freudienne du rêve comme rébus, comme rhétorique et comme peinture permet d'engager une réflexion sur l'image et le mot considérés comme signifiants. Dans le rêve comme dans la peinture, le va et vient entre l'image et le mot est assuré par des processus trans-systématiques qui ne sont autres que la condensation, le déplacement et la prise en considération de la figurabilité. Ce va et vient entre l'image et le mot trouve ses limites avec l'indicible et l'infigurable. La figure logique de la négation, possible dans le champ linguistique est un point irreprésentable dans l'inconscient comme sur le tableau. Elle apparaît comme un des noms de la catégorie du Réel.[Résumé en anglais]This dissertation attempts to determine what place can be attributed within the Lacanian field to the process of figuration in the dream, such as it was revealed by Freud. The Freudian definition of the dream as a rebus, as a rhetorical structure and as a painting induces a reflection on the image and the word considered as signifiers. In the dream as well as in the painting, the reciprocal movement between the image and the word is assured by trans-systematic processes that are no other than condensation, displacement and the consideration of figurability. This to and fro between the image and the word finds its limit with the un-utterable and the un-figurable. The logical figure of negation, possible in the linguistic field, is an unrepresentable point in the unconscious, as well as in the painting. It emerges as one of the names of the Real.ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF

Structure psychanalytique des paradoxes

La psychanalyse démontre que c'est dans la structure d'un paradoxe que la Science atteint le Réel, et que, par effet de retour, cette connexion fournit quelques métaphores, modèles et structures propres à corroborer l'efficace de l'acte psychanalytique. Le Réel du Symbolique et le Symbolique du Réel se croisent, voire se traversent topo-logiquement.D'où ceci, que le trait de craie sur un tableau, par exemple, se décompose, dans le contexte de la physique quantique, en molécules, résultats d'un assemblage d'atomes, composés eux-mêmes de particules élémentaires, soit ce niveau d'organisation du Réel inextricablement appareillé à la formalisation mathématique qui l'objective. Il suffit alors de réaliser que le formalisme en question consiste lui-même en traits de craie, pour que l'épiphanie, au sens joycien, s'actualise.Paradoxe des paradoxes, le présent travail de thèse consiste ainsi dans la mise à l'épreuve de la Science au regard du Réel psychanalytique.ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF

Le secret, chiffre et déchiffre-ment (lecture psychanalytique du secret dans l'Oedipe Roi de Sophocle)

[Résumé en français]On distingue le secret dans le champ psychanalytique à partir d'une cohorte d'acceptions qui, le plus souvent, porte à confusion. Se dégage ainsi l'idée d'un secret dont la valeur propre serait de confiner une vérité inaudible et indicible à un retrait illimité. En parcourant la littérature ou les sciences, il s'avère qu'un tel secret se supporte prioritairement d'un chiffre. Renvoyé au champ de l'écriture, Freud nous aide à appréhender ce secret à travers l'interprétation des rêves, le déchiffrement des hiéroglyphes et l'exemplarité de l'Œdipe Roi. Le texte de Sophocle témoigne de la circulation du secret mais aussi de la révélation comme un moment dévastateur pour le sujet. Ceci pose la question de ce qui pourrait s'entendre du secret dans la cure. On revient alors, avec l'aide de Lacan et de Freud, au déchiffrement comme une lecture possible du secret, permettant l'arrimage du sujet et l'articulation d'une position désirante.[Résumé en anglais]The secret, in the psychoanalytic field, is distinguished from a wide range of possibilities which more often lead to confusion. It emerges into an idea of a secret of which the inner value would confine to an inaudible and unspeakable truth sent back to an unlimited withdrawal. Travelling through literature and sciences, it is established that such secret, mainly, hold up through a cipher. Sent back to the writing field, Freud helps us to apprehend this secret through the interpretation of dreams, the deciphering of hieroglyphics and the exemplary nature of Œdipus the king. The text by Sophocles witnesses the circulation of the secret but also the revelation as a devastating experience for the subject. This rises the question about the listening of this secret in the cure. Therefore we go back, with the helps of Lacan and Freud, to deciphering as being a possible reading of the secret, allowing the subject's stowing and the articulation of a position where the subject is experiencing what desire is.ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF

Fréquences des dysthyroïdies chez des adultes inclus dans l’étude SU.VI.MAX, France, 1994 – 1995

info:eu-repo/semantics/nonPublishe

A study of the association between UGT1A1*28 variant allele of UGT1A1 gene and colonic phenotype of sporadic colorectal cancer

International audienceINTRODUCTION: The transcriptional activity of the UGT1A1 gene is modulated by a variable number of repetitions of the dinucleotide (TA) within its promoter region. By comparison to the most common allele (TA)6 (UGT1A1*1), decreased activity is observed with increasing TA repetitions. The aim of this study was to determine whether the presence of the variant allele UGT1A1*28, harbouring seven TA repetitions, (TA)7, in the homozygous state, is associated with precancerous colonic lesions and/or with specific colorectal cancer characteristics. MATERIAL AND METHODS: All patients treated for colorectal cancer in a tertiary care centre, between January 2009 and December 2013, who had routine UGT1A1 genotyping for irinotecan dose-adjustment were included. Data were retrospectively collected. RESULTS: 292 patients were enrolled, including 23 UGT1A1*28/*28 homozygous (7.9%), 137 wild type homozygous (46.9%) and 132 heterozygous (45.2%). There were no significant differences in phenotypic colonic characteristics between homozygous and heterozygous patients carrying the UGT1A1*28 allele as compared to *1/*1 homozygous. Patients treated with aspirin were significantly more common in the UGT1A1*28/*28 homozygous group than in the other groups (7/23 (30.4%) compared to 22/269 (8.2%), p = 0.001). CONCLUSION: Dinucleotide polymorphism in the promoter region of the UGT1A1 gene is not associated with a specific colonic phenotype in patients with sporadic colorectal cancer

Evaluation of the interest to combine a CD4 Th1-inducer cancer vaccine derived from telomerase and atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: a randomized non-comparative phase II study (TERTIO – PRODIGE 82)

Abstract Background Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non–small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. Methods Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. Discussion Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. Trial registration NCT05528952