Development of selective inhibitors of transglutaminase: phenylthiourea derivatives

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A Focused Sequent Calculus Framework for Proof Search in Pure Type Systems

Basic proof-search tactics in logic and type theory can be seen as the root-first applications of rules in an appropriate sequent calculus, preferably without the redundancies generated by permutation of rules. This paper addresses the issues of defining such sequent calculi for Pure Type Systems (PTS, which were originally presented in natural deduction style) and then organizing their rules for effective proof-search. We introduce the idea of Pure Type Sequent Calculus with meta-variables (PTSCalpha), by enriching the syntax of a permutation-free sequent calculus for propositional logic due to Herbelin, which is strongly related to natural deduction and already well adapted to proof-search. The operational semantics is adapted from Herbelin's and is defined by a system of local rewrite rules as in cut-elimination, using explicit substitutions. We prove confluence for this system. Restricting our attention to PTSC, a type system for the ground terms of this system, we obtain the Subject Reduction property and show that each PTSC is logically equivalent to its corresponding PTS, and the former is strongly normalising iff the latter is. We show how to make the logical rules of PTSC into a syntax-directed system PS for proof-search, by incorporating the conversion rules as in syntax-directed presentations of the PTS rules for type-checking. Finally, we consider how to use the explicitly scoped meta-variables of PTSCalpha to represent partial proof-terms, and use them to analyse interactive proof construction. This sets up a framework PE in which we are able to study proof-search strategies, type inhabitant enumeration and (higher-order) unification

A deep proper-motion survey of the nearby open cluster Blanco 1

We provide two comprehensive catalogues of positions and proper motions in the area of open cluster Blanco 1. The main catalogue, CtlgM, contains 6271 objects down to V∼ 18.5 and covers a circular ∼11 deg2 area. The accuracy of CtlgM proper motions, at about 0.3-0.5 mas yr−1 for well-measured stars, permits an excellent segregation between the cluster and field stars. The vector-point diagram of proper motions indicates an estimated total of ∼165 cluster members among the stars in our sample, while 314 stars with σμ < 2.5 mas yr−1 have membership probabilities Pμ≥ 1 per cent. We also explored the astrometric potential of the Catalogue of Objects and Measured Parameters from All Sky Surveys (COMPASS) data base in order to obtain additional proper motions for fainter stars in the area of Blanco 1. This effort produced the second catalogue of proper motions, CtlgD, containing 11 598 objects down to V∼ 21. A total of 4273 objects are common between the two catalogues. The accuracy of proper motions in CtlgD ranges from 1.0 to 6 mas yr−1. A combination of both proper-motion catalogues was instrumental in confirming that Blanco 1 contains a large population of M dwarfs (∼150 down to M5 V - the limit of our survey). In many respects, Blanco 1 is a scaled down ‘twin' of the Pleiades. The noted discrepancy between the distance from a new Hipparcos parallax of Blanco 1 and the cluster's photometric distance, at least partially, might be due to the apparent correlation between parallax and proper motion in right ascension for the ensemble of cluster member

Atlantic Leatherback Migratory Paths and Temporary Residence Areas

BACKGROUND: Sea turtles are long-distance migrants with considerable behavioural plasticity in terms of migratory patterns, habitat use and foraging sites within and among populations. However, for the most widely migrating turtle, the leatherback turtle Dermochelys coriacea, studies combining data from individuals of different populations are uncommon. Such studies are however critical to better understand intra- and inter-population variability and take it into account in the implementation of conservation strategies of this critically endangered species. Here, we investigated the movements and diving behaviour of 16 Atlantic leatherback turtles from three different nesting sites and one foraging site during their post-breeding migration to assess the potential determinants of intra- and inter-population variability in migratory patterns. METHODOLOGY/PRINCIPAL FINDINGS: Using satellite-derived behavioural and oceanographic data, we show that turtles used Temporary Residence Areas (TRAs) distributed all around the Atlantic Ocean: 9 in the neritic domain and 13 in the oceanic domain. These TRAs did not share a common oceanographic determinant but on the contrary were associated with mesoscale surface oceanographic features of different types (i.e., altimetric features and/or surface chlorophyll a concentration). Conversely, turtles exhibited relatively similar horizontal and vertical behaviours when in TRAs (i.e., slow swimming velocity/sinuous path/shallow dives) suggesting foraging activity in these productive regions. Migratory paths and TRAs distribution showed interesting similarities with the trajectories of passive satellite-tracked drifters, suggesting that the general dispersion pattern of adults from the nesting sites may reflect the extent of passive dispersion initially experienced by hatchlings. CONCLUSIONS/SIGNIFICANCE: Intra- and inter-population behavioural variability may therefore be linked with initial hatchling drift scenarios and be highly influenced by environmental conditions. This high degree of behavioural plasticity in Atlantic leatherback turtles makes species-targeted conservation strategies challenging and stresses the need for a larger dataset (>100 individuals) for providing general recommendations in terms of conservation

Active ecological restoration of cold-water corals: techniques, challenges, costs and future directions

Cold-water coral (CWC) habitats dwell on continental shelves, slopes, seamounts, and ridge systems around the world's oceans from 50 to 4000 m depth, providing heterogeneous habitats which support a myriad of associated fauna. These highly diverse ecosystems are threatened by human stressors such as fishing activities, gas and oil exploitation, and climate change. Since their life-history traits such as long lifespan and slow growth rates make CWCs very vulnerable to potential threats, it is a foremost challenge to explore the viability of restoration actions to enhance and speed up their recovery. In contrast to terrestrial and shallow-water marine ecosystems, ecological restoration in deep marine environments has received minimal attention. This review, by means of a systematic literature search, aims to identify CWC restoration challenges, assess the most suitable techniques to restore them, and discuss future perspectives. Outcomes from the few restoration actions performed to date on CWCs, which have lasted between 1 to 4 years, provide evidence of the feasibility of coral transplantation and artificial reef deployments. Scientific efforts should focus on testing novel and creative restoration techniques, especially to scale up to the spatial and temporal scales of impacts. There is still a general lack of knowledge about the biological, ecological and habitat characteristics of CWC species exploration of which would aid the development of effective restoration measures. To ensure the long-term viability and success of any restoration action it is essential to include holistic and long-term monitoring programs, and to ideally combine active restoration with natural spontaneous regeneration (i.e., passive restoration) strategies such as the implementation of deep-sea marine protected areas (MPAs). We conclude that a combination of passive and active restoration approaches with involvement of local society would be the best optimal option to achieve and ensure CWC restoration success

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts