Of bits and bugs

Pur-α is a nucleic acid-binding protein involved in cell cycle control, transcription, and neuronal function. Initially no prediction of the three-dimensional structure of Pur-α was possible. However, recently we solved the X-ray structure of Pur-α from the fruitfly Drosophila melanogaster and showed that it contains a so-called PUR domain. Here we explain how we exploited bioinformatics tools in combination with X-ray structure determination of a bacterial homolog to obtain diffracting crystals and the high-resolution structure of Drosophila Pur-α. First, we used sensitive methods for remote-homology detection to find three repetitive regions in Pur-α. We realized that our lack of understanding how these repeats interact to form a globular domain was a major problem for crystallization and structure determination. With our information on the repeat motifs we then identified a distant bacterial homolog that contains only one repeat. We determined the bacterial crystal structure and found that two of the repeats interact to form a globular domain. Based on this bacterial structure, we calculated a computational model of the eukaryotic protein. The model allowed us to design a crystallizable fragment and to determine the structure of Drosophila Pur-α. Key for success was the fact that single repeats of the bacterial protein self-assembled into a globular domain, instructing us on the number and boundaries of repeats to be included for crystallization trials with the eukaryotic protein. This study demonstrates that the simpler structural domain arrangement of a distant prokaryotic protein can guide the design of eukaryotic crystallization constructs. Since many eukaryotic proteins contain multiple repeats or repeating domains, this approach might be instructive for structural studies of a range of proteins

Unrestricted quantum moduli algebras, III: Surfaces of arbitrary genus and skein algebras

We prove that the quantum moduli algebra associated to a possibly punctured compact oriented surface and a complex semisimple Lie algebra $\mathfrak{g}$ is a Noetherian and finitely generated ring; if the surface has punctures, we prove also that it has no non-trivial zero divisors. Moreover, we show that the quantum moduli algebra is isomorphic to the skein algebra of the surface, defined by means of the Reshetikhin-Turaev functor for the quantum group $U_q(\mathfrak{g})$, and which coincides with the Kauffman bracket skein algebra when $\mathfrak{g}=\mathfrak{sl}_2$.Comment: V1: 60 pages, 26 figures; V2: 75 pages, 37 figures, with typos corrected, section 6. 3 rewritten with simpler arguments and a new result (Corollary 6.12), and section 7 added, with results about the quantum reductio

Total synthesis of cyclotheonamide C using a tandem backbone-extension-coupling methodology

International audienceNo abstrac

From Terminology Extraction to Terminology Validation: An Approach Adapted to Log Files

International audienceLog files generated by computational systems contain relevant and essential information. In some application areas like the design of integrated circuits, log files generated by design tools contain information which can be used in management information systems to evaluate the final products. However, the complexity of such textual data raises some challenges concerning the extraction of information from log files. Log files are usually multi-source, multi-format, and have a heterogeneous and evolving structure. Moreover, they usually do not respect natural language grammar and structures even though they are written in English. Classical methods of information extraction such as terminology extraction methods are particularly irrelevant to this context. In this paper, we introduce our approach Exterlog to extract terminology from log files. We detail how it deals with the specific features of such textual data. The performance is emphasized by favoring the most relevant terms of the domain based on a scoring function which uses a Web and context based measure. The experiments show that Exterlog is a well-adapted approach for terminology extraction from log files

Semi-Rigid Moment-Resisting Behavior of Multiple Tab-and-Slot Joint for Freeform Timber Plate Structures

Historically based on the transfer of ancestral know-how, the art of carpentry changed considerably at the beginning of the 21st century with the arrival on the market of engineered wood products (EWP) and computer numerically controlled machines (CNC). The development of these wood products was initially started for the needs of aeronautics : lightweight panels but with high structural capacity. It is also in this field that automated multi-axis milling machines and the accompanying computing tool, computer-aided design and manufacturing (CAD / CAM), have begun to be developed to produce more complex mechanical parts. It was also in the early 2000s that several teams of researchers in the field of computer graphics but also in architecture were interested in complex free forms. One of the many challenges is still the discretization with planar elements of doubly curved surfaces oriented freely in space. The encounter of these `` algorithms '' with the high-performant wood panels was ineluctable. However, the assembly of polygonal panels in space to form a structure is not trivial. Optimization efforts are made so that the topology in itself favors the distribution of forces to tend towards a behavior of shells. But the problem is sometimes insoluble for very irregular shapes alternating negative, zero and positive Gaussian curvatures. To ensure the transmission of the axial, shear and bending internal forces induced by vertical or horizontal external loads, whether symmetrical or not, the performance of the assemblies used to connect these panels by their edges becomes paramount. In wood construction, this is a topic currently being studied by a few research laboratories including EPFL for innovative wood-to-wood joints with multiple tab and slots (MTSJ). The main difficulty lies in how to connect thin wood panels with the best stiffness and strength. In the recent past, the assembly of wood parts between them, often with metal fasteners to provide a certain ductility, was assimilated to a hinge. With the new standards like the Eurocodes, the notion of semi-rigidity is now essential to obtain a realistic response of structures to both ultimate and service limit states. The solution proposed at IBOIS enters into this new context. It allows, without glue or metallic connectors, to interconnect thin engineered wood panels, ensuring both locator and connector features and the transfer of multidirectional forces. This thesis focuses on the semi-rigid moment resisting behavior of the through tenon variant (TT) with closed slots. The numerous experiments conducted during this study demonstrated the ability of this variant to compete with screws to resist a moment around the angularly connected edges. The joint is directly generated during the multiaxial cutting of laminated veneer lumber(LVL) panels which include a certain percentage of cross-layers. From a structural point of view, the local mechanical study under a bending moment was inspired by a wood-to-wood joint in service in the ancestral Japanese shrines, the "Nuki" joint. Analyzed by Japanese researchers as it historically participates in the resilience of their ancestral constructions to typhoons and earthquakes, it activates embedment mechanisms of wood in rotational partial compression (RPC) to resist the moment resulting from the external loads. It is these mechanisms that are taken into account for through tenon variant. ..

Interest of major serum protein removal for Surface-Enhanced Laser Desorption/Ionization – Time Of Flight (SELDI-TOF) proteomic blood profiling

BACKGROUND: Surface-Enhanced Laser Desorption/Ionization – Time Of Flight (SELDI-TOF) has been proposed as new approach for blood biomarker discovery. However, results obtained so far have been often disappointing as this technique still has difficulties to detect low-abundant plasma and serum proteins. RESULTS: We used a serum depletion scheme using chicken antibodies against various abundant proteins to realized a pre-fractionation of serum prior to SELDI-TOF profiling. Depletion of major serum proteins by immunocapture was confirmed by 1D and 2D gel electrophoresis. SELDI-TOF analysis of bound and unbound (depleted) serum fractions revealed that this approach allows the detection of new low abundant protein peaks with satisfactory reproducibility. CONCLUSION: The combination of immunocapture and SELDI-TOF analysis opens new avenues into proteomic profiling for the discovery of blood biomarkers

Multiple Tab-and-Slot Joint : Improvement of the Rotational Stiffness for the Connection of Thin Structural Wood Panels

Researchers in Asia have focused on analyzing the rotational performance of traditional connections based on embedment. The Nuki through-joint has inspired work at the laboratory of wood construction (IBOIS), Ecole Polytechnique Fédérale de Lausanne, to improve the rotational behavior of the multiple tab and slot joint (MTSJ). In this work, through tenon (TT) and closed slot joints were added to initial dovetail and Nejiri arigata joints used for foldedplate structures. The bending performance of the improved MTSJ-TT joint was higher than that of screwed angular connections. Numerical monitoring of the embedded volumes under partial compression on the contact surfaces was used to characterize the directly and indirectly loaded areas. The decay coefficients for the exponential form, which defined the additional length in the indirectly loaded area, were quantified for both single (SC) and double contact (DC). The evolution of these coefficients was also monitored along the angular deformation. Finally, an analytical formulation of the embedded volumes was provided to prepare an analytical model for the MTSJ-TT joint subjected to bending

Characterization of Monomeric Intermediates during VSV Glycoprotein Structural Transition

Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformational changes of viral glycoproteins. Crystal structures provide static pictures of pre- and post-fusion conformations of these proteins but the transition pathway remains elusive. Here, using several biophysical techniques, including analytical ultracentrifugation, circular dichroïsm, electron microscopy and small angle X-ray scattering, we have characterized the low-pH-induced fusogenic structural transition of a soluble form of vesicular stomatitis virus (VSV) glycoprotein G ectodomain (Gth, aa residues 1–422, the fragment that was previously crystallized). While the post-fusion trimer is the major species detected at low pH, the pre-fusion trimer is not detected in solution. Rather, at high pH, Gth is a flexible monomer that explores a large conformational space. The monomeric population exhibits a marked pH-dependence and adopts more elongated conformations when pH decreases. Furthermore, large relative movements of domains are detected in absence of significant secondary structure modification. Solution studies are complemented by electron micrographs of negatively stained viral particles in which monomeric ectodomains of G are observed at the viral surface at both pH 7.5 and pH 6.7. We propose that the monomers are intermediates during the conformational change and thus that VSV G trimers dissociate at the viral surface during the structural transition