Construction des profils utilisateurs à base d'une ontologie pour une recherche d'information personnalisée.

16 pagesNational audienceLa recherche d'information (RI) personnalisée tend principalement à modéliser l'utilisateur selon un profil puis à l'intégrer dans la chaîne d'accès à l'information, afin de mieux répondre à ses besoins spécifiques. Ce papier présente une extension d'une approche de construction implicite du profil utilisateur précédemment développée où les centres d'intérêts sont représentés à base de termes pondérés. L'extension de cette approche permet d'obtenir une représentation sémantique de ces centres à base de concepts pondérés en utilisant l'ontologie de l'ODP. Nous avons évalué notre approche sur la collection de documents TREC et avons présenté quelques résultats expérimentaux mettant en évidence l'impact de l'intégration du profil utilisateur sur la performance du système

Intrinsically disordered energy landscapes.

Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such 'intrinsically disordered' landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an α-helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.The authors thank Prof. Jane Clarke, Dr. Chris Whittleston, Dr. Joanne Carr, Dr. Iskra Staneva and Dr. David de Sancho for helpful discussions. Y.C. and A.J.B. acknowledge funding from the EPSRC grant number EP/I001352/1, D.C. gratefully acknowledges the Cambridge Commonwealth European and International Trust for financial support and D.J.W. the ERC for an Advanced Grant.This is the final version. It was first published by NPG at http://www.nature.com/srep/2015/150522/srep10386/full/srep10386.html?WT.ec_id=SREP-639%2C638-20150526#abstract

Crucial role of nonspecific interactions in amyloid nucleation.

Protein oligomers have been implicated as toxic agents in a wide range of amyloid-related diseases. However, it has remained unsolved whether the oligomers are a necessary step in the formation of amyloid fibrils or just a dangerous byproduct. Analogously, it has not been resolved if the amyloid nucleation process is a classical one-step nucleation process or a two-step process involving prenucleation clusters. We use coarse-grained computer simulations to study the effect of nonspecific attractions between peptides on the primary nucleation process underlying amyloid fibrillization. We find that, for peptides that do not attract, the classical one-step nucleation mechanism is possible but only at nonphysiologically high peptide concentrations. At low peptide concentrations, which mimic the physiologically relevant regime, attractive interpeptide interactions are essential for fibril formation. Nucleation then inevitably takes place through a two-step mechanism involving prefibrillar oligomers. We show that oligomers not only help peptides meet each other but also, create an environment that facilitates the conversion of monomers into the β-sheet-rich form characteristic of fibrils. Nucleation typically does not proceed through the most prevalent oligomers but through an oligomer size that is only observed in rare fluctuations, which is why such aggregates might be hard to capture experimentally. Finally, we find that the nucleation of amyloid fibrils cannot be described by classical nucleation theory: in the two-step mechanism, the critical nucleus size increases with increases in both concentration and interpeptide interactions, which is in direct contrast with predictions from classical nucleation theory.This is the accepted manuscript. The final published version is available from PNAS at http://www.pnas.org/content/111/50/17869.abstract

NR3E receptors in cnidarians : a new family of steroid receptor relatives extends the possible mechanisms for ligand binding

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Journal of Steroid Biochemistry and Molecular Biology 184 (2018): 11-19, doi:10.1016/j.jsbmb.2018.06.014.Steroid hormone receptors are important regulators of development and physiology in bilaterian animals, but the role of steroid signaling in cnidarians has been contentious. Cnidarians produce steroids, including A-ring aromatic steroids with a side-chain, but these are probably made through pathways different than the one used by vertebrates to make their A-ring aromatic steroids. Here we present comparative genomic analyses indicating the presence of a previously undescribed nuclear receptor family within medusozoan cnidarians, that we propose to call NR3E. This family predates the diversification of ERR/ER/SR in bilaterians, indicating that the first NR3 evolved in the common ancestor of the placozoan and cnidarian-bilaterian with lineage-specific loss in the anthozoans, even though multiple species in this lineage have been shown to produce aromatic steroids, whose function remain unclear. We discovered serendipitously that a cytoplasmic factor within epidermal cells of transgenic Hydra vulgaris can trigger the nuclear translocation of heterologously expressed human ERα. This led us to hypothesize that aromatic steroids may also be present in the medusozoan cnidarian lineage, which includes Hydra, and may explain the translocation of human ERα. Docking experiments with paraestrol A, a cnidarian A-ring aromatic steroid, into the ligand-binding pocket of Hydra NR3E indicates that, if an aromatic steroid is indeed the true ligand, which remains to be demonstrated, it would bind to the pocket through a partially distinct mechanism from the manner in which estradiol binds to vertebrate ER.KK is supported by grant from Japan Society for the Promotion of Science (JSPS 17K07420). I.M.L.B and Y.C. acknowledge the support and the use of resources of the French Infrastructure for Integrated Structural Biology FRISBI ANR-10-INBS-05 and of Instruct-ERIC. AMR was supported by NIH Award R15GM114740. AMT was supported by an Internal Research and Development Award from the Woods Hole Oceanographic Institution

On the Complexity of the Maximum Independent Set Reconfiguration Problem

We study the complexity of the polynomially equivalent Minimum Vertex Cover Reconfiguration and Maximum Independent Set Reconfiguration problems on a variety of graph classes, which ask whether there exists a reconfiguration sequence between two minimum vertex covers/maximum independent sets S and T of a graph G. The problems are studied under the token jumping and token sliding models, which turn out to be equivalent in this context. We show that the problems are in P when restricted to bipartite graphs, PSPACE-complete when restricted to planar graphs, as well as a list of results on a variety of other graph classes

A multifunnel energy landscape encodes the competing α-helix and β-hairpin conformations for a designed peptide.

Depending on the amino acid sequence, as well as the local environment, some peptides have the capability to fold into multiple secondary structures. Conformational switching between such structures is a key element of protein folding and aggregation. Specifically, understanding the molecular mechanism underlying the transition from an α-helix to a β-hairpin is critical because it is thought to be a harbinger of amyloid assembly. In this study, we explore the energy landscape for an 18-residue peptide (DP5), designed by Araki and Tamura to exhibit equal propensities for the α-helical and β-hairpin forms. We find that the degeneracy is encoded in the multifunnel nature of the underlying free energy landscape. In agreement with experiment, we also observe that mutation of tyrosine at position 12 to serine shifts the equilibrium in favor of the α-helix conformation, by altering the landscape topography. The transition from the α-helix to the β-hairpin is a complex stepwise process, and occurs via collapsed coil-like intermediates. Our findings suggest that even a single mutation can tune the emergent features of the landscape, providing an efficient route to protein design. Interestingly, the transition pathways for the conformational switch seem to be minimally perturbed upon mutation, suggesting that there could be universal microscopic features that are conserved among different switch-competent protein sequences.erc epsrc Cambridge Commonwealth, European, and International Trust

A LIMIT STATE FUNCTION FOR PIPELINES CONTAINING LONG CORROSION DEFECTS

ABSTRACT Currently, there exist various models that predict the burst capacity of a pipeline containing corrosion defects. Recent studies have indicated that these models tend to be overly conservative for long corrosion defects. This paper, based on a PRCI-sponsored study, aims at minimizing this conservatism through a series of steps. First, different definitions for long corrosion defects prevalent in the literature were examined and compared, and the most suitable criterion was implemented. Next, three existing burst pressure models for general corrosion defects were identified and evaluated: ASME B31G-modified, a model developed at C-FER and a model developed at the University of Waterloo. The suitability of these models for long corrosion defects was assessed using a database of 50 full-scale burst test specimens containing natural long corrosion defects. Finally, based on this evaluation, the most apposite burst pressure prediction model for long corrosion defects was selected and a corresponding model error factor was derived

A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya – either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome.Life Sciences Research FoundationHoward Hughes Medical Institut

Influence of intraoral scanner and finish line location on the fabrication trueness and margin quality of additively manufactured laminate veneers fabricated with a completely digital workflow.

STATEMENT OF PROBLEM Knowledge of the fabrication trueness and margin quality of additively manufactured (AM) laminate veneers (LVs) when different intraoral scanners (IOSs) and finish line locations are used is limited. PURPOSE The purpose of this in vitro study was to evaluate the fabrication trueness and margin quality of AM LVs with different finish line locations digitized by using different IOSs. MATERIAL AND METHODS An LV preparation with a subgingival (sub), equigingival (equi), or supragingival (supra) finish line was performed on 3 identical maxillary right central incisor typodont teeth. Each preparation was digitized by using 2 IOSs, (CEREC Primescan [PS] and TRIOS 3 [TS]), and a reference LV for each finish line-IOS pair (n=6) was designed. A total of 90 LVs were fabricated by using these files and urethane acrylate-based definitive resin (Tera Harz TC-80DP) (n=15). Each LV was then digitized by using PS to evaluate fabrication trueness (overall, external, intaglio, and marginal surfaces). Each LV was also qualitatively evaluated under a stereomicroscope (×60), and the cervical and incisal margin quality was graded. Fabrication trueness and cervical margin quality were evaluated by using 2-way analysis of variance, while Kruskal-Wallis and Mann Whitney-U tests were used to evaluate incisal margin quality (α=.05). RESULTS The interaction between the IOS type and the finish line location affected measured deviations at each surface (P≤.020). PS-sub and TS-supra had higher overall trueness than their counterparts. and the subgingival finish line resulted in the lowest trueness (P≤.005). PS and the subgingival finish line led to the lowest trueness of the external surface (P≤.001). TS-sub had the lowest intaglio surface trueness among the TS subgroups, and PS-sub had higher trueness than TS-sub (P<.001). PS-sub and PS-supra had higher marginal surface trueness than their TS counterparts (P<.001). TS resulted in higher cervical margin quality (P=.001). CONCLUSIONS Regardless of the IOS tested, subgingival finish lines resulted in the lowest trueness. The effect of IOS on the measured deviations varied according to the surface evaluated and finish line location. The cervical margin quality of AM LVs was higher when TS was used