Foundations for a Combination of Heterogeneous Specification Components

In this paper, we advocate an approach to combine formal specification components. Our work aims at building or reusing specification components, and compose them with a gluing language constituted of a minimal but sufficient set of operators. The glue allows to have at one's disposal a global formal specification with heterogeneous components as basic entities. The interests are manifold: modelling the different aspects of systems, allowing the use of many existing specification languages, formalizing the links between components in an easy and graphical way, making the reuse of components easier. A case study about a vending machine is specified to illustrate how this approach could be practically used.     

Prediction of water temperature heterogeneity of braided rivers using very high resolution thermal infrared (TIR) images

Braided rivers exhibit high spatial thermal heterogeneity that is difficult to understand using only in situ measurements. In this summer study, we used a drone and a powered paraglider to acquire very high spatial resolution (14–27 cm) thermal infrared (TIR) images of nine braided reaches located in the French Alps. We applied atmospheric corrections to TIR images and calibrated them based on in situ data. To characterize spatial and temporal thermal patterns, three temporal approaches were applied. A single survey of each site was performed to comparatively explore the nine braided reaches. Three reaches were imaged twice, in 2010 and 2011, to explore inter-annual variability. Finally, two reaches were selected for an intra-day survey for which four and three flights, respectively, were realized within one day. We reported two types of thermal patterns in braided reaches, the first showing very low thermal variability throughout the day. This low variability was linked to the low diversity found in the aquatic habitat, notably due to proglacial regimes with high summer flows which homogenize water temperatures. The second type exhibited a higher thermal variability with changes during the day. The temperature of flowing channels changed during the daytime according to air temperature. In contrast, the temperature of channels downstream connected to the main network exhibited smaller changes, which created thermal variability over space and time associated with hyporheic or phreatic flows. Non-proglacial and proglacial reaches behaved differently according to air temperature. Proglacial reaches were colder and less sensitive to air temperature in comparison with non-proglacial reaches. These findings allow for a prediction of habitat diversity from temperature heterogeneity based on time and the proportion of ponds, alluvial, and groundwater channels.     

pH-dependent specific binding and combing of DNA

Recent developments in the rapid sequencing, mapping, and analysis of DNA rely on the specific binding of DNA to specially treated surfaces. We show here that specific binding of DNA via its unmodified extremities can be achieved on a great variety of surfaces by a judicious choice of the pH. On hydrophobic surfaces the best binding efficiency is reached at a pH of approximately 5.5. At that pH a approximately 40-kbp DNA is 10 times more likely to bind by an extremity than by a midsegment. A model is proposed to account for the differential adsorption of the molecule extremities and midsection as a function of pH. The pH-dependent specific binding can be used to align anchored DNA molecules by a receding meniscus, a process called molecular combing. The resulting properties of the combed molecules will be discussed.     

Complex geometry macroporous SiC ceramics obtained by 3D-printing,polymer impregnation and pyrolysis (PIP) and chemical vapor deposition (CVD)

We present here an original route for the manufacturing of SiC ceramics based on 3D printing, polymer impregnation and pyrolysis and chemical vapor deposition (CVD). The green porous elastomer structures were first prepared by fused deposition modeling (FDM) 3D-printing with a composite polyvinyl alcohol/elastomer wire and soaking in water, then impregnated with an allylhydridopolycarbosilane preceramic polymer. After crosslinking and pyrolysis, the polymer-derived ceramics were reinforced by CVD of SiC using CH₃SiCl₃/H₂ as precursor. The multiscale structure of the SiC porous specimens was examined by X-ray tomography and scanning electron microscopy analyses. Their oxidation resistance was also studied. The pure and dense CVD-SiC coating considerably improves the oxidation resistance.     

Stretched and overwound DNA forms a Pauling-like structure with exposed bases

We investigate structural transitions within a single stretched and supercoiled DNA molecule. With negative supercoiling, for a stretching force >0.3 pN, we observe the coexistence of B-DNA and denatured DNA from sigma approximately -0.015 down to sigma = -1. Surprisingly, for positively supercoiled DNA (sigma > +0.037) stretched by 3 pN, we observe a similar coexistence of B-DNA and a new, highly twisted structure. Experimental data and molecular modeling suggest that this structure has approximately 2.62 bases per turn and an extension 75% larger than B-DNA. This structure has tightly interwound phosphate backbones and exposed bases in common with Pauling's early DNA structure [Pauling, L. & Corey, R. B. (1953), Proc. Natl. Acad. Sci. USA 39, 84-97] and an unusual structure proposed for the Pf1 bacteriophage [Liu, D. J. & Day, L. A. (1994) Science 265, 671-674].     

Design,Synthesis and Evaluation of a Series of 1,5-Diaryl-1,2,3-triazole-4-carbohydrazones as Inhibitors of the YAP-TAZ/TEAD Complex

Starting from our previously reported hit, a series of 1,5-diaryl-1,2,3-triazole-4-carbohydrazones were synthesized and evaluated as inhibitors of the YAP/TAZ-TEAD complex. Their binding to hTEAD2 was confirmed by nanodifferential scanning fluorimetry, and some of the compounds were also found to moderately disrupt the YAP-TEAD interaction, as assessed by a fluorescence polarization assay. A TEAD luciferase gene reporter assay performed in HEK293T cells and RTqPCR measurements in MDA-MB231 cells showed that these compounds inhibit YAP/TAZ-TEAD activity to cells in the micromolar range. In spite of the cytotoxic effects displayed by some of the compounds of this series, they are still good starting points and can be suitably modified into an effective and viable YAP-TEAD disruptor in the future.     

Site-Specific Isotopic Labeling (SSIL): Access to High-Resolution Structural and Dynamic Information in Low-Complexity Proteins

Remarkable technical progress in the area of structural biology has paved the way to study previously inaccessible targets. For example, large protein complexes can now be easily investigated by cryo-electron microscopy, and modern high-field NMR magnets have challenged the limits of high-resolution characterization of proteins in solution. However, the structural and dynamic characteristics of certain proteins with important functions still cannot be probed by conventional methods. These proteins in question contain low-complexity regions (LCRs), compositionally biased sequences where only a limited number of amino acids is repeated multiple times, which hamper their characterization. This Concept article describes a site-specific isotopic labeling (SSIL) strategy, which combines nonsense suppression and cell-free protein synthesis to overcome these limitations. An overview on how poly-glutamine tracts were made amenable to high-resolution structural studies is used to illustrate the usefulness of SSIL. Furthermore, we discuss the potential of this methodology to give further insights into the roles of LCRs in human pathologies and liquid–liquid phase separation, as well as the challenges that must be addressed in the future for the popularization of SSIL.     

Synthesis of Cu–Pd alloy thin films by co-electrodeposition

This paper presents results on the synthesis of Cu–Pd alloy thin films on Ti substrates by co-electrodeposition of Pd and Cu from nitrate-base electrolytic baths. The deposition rates of Cu and Pd were determined by Electrochemical Quartz Crystal Microbalance as a function of the electrode potential and Cu⁺² and Pd⁺² concentrations. It is shown that electrodeposition of copper and palladium occurs simultaneously at −0.50 V vs. SCE and that Cu–Pd thin films over the entire composition range were obtained by changing the composition of the solution. X-ray diffraction analyses indicated that these films have a nanocrystalline single-phase face-centered cubic structure and scanning electron microscopy analyses showed that potentiostatically deposited films are rough and porous, which is appropriate for electrocatalysis applications. In an attempt to get denser deposits as required for H₂ purification applications, pulsed potential co-electrodeposition was performed and the effect of the deposition conditions on the roughness of the films was assessed by double layer capacitance measurements. It was shown that smooth Cu–Pd films (with R_f value as low as 8, as opposed to more than 120 for films prepared in the potentiostatic mode) could be obtained with a proper choice on the deposition conditions.     

Behavior of supercoiled DNA

We study DNA supercoiling in a quantitative fashion by micromanipulating single linear DNA molecules with a magnetic field gradient. By anchoring one end of the DNA to multiple sites on a magnetic bead and the other end to multiple sites on a glass surface, we were able to exert torsional control on the DNA. A rotating magnetic field was used to induce rotation of the magnetic bead, and reversibly over- and underwind the molecule. The magnetic field was also used to increase or decrease the stretching force exerted by the magnetic bead on the DNA. The molecule's degree of supercoiling could therefore be quantitatively controlled and monitored, and tethered-particle motion analysis allowed us to measure the stretching force acting on the DNA. Experimental results indicate that this is a very powerful technique for measuring forces at the picoscale. We studied the effect of stretching forces ranging from 0.01 pN to 100 pN on supercoiled DNA (-0.1 < sigma < 0.2) in a variety of ionic conditions. Other effects, such as stretching-relaxing hysteresis and the braiding of two DNA molecules, are discussed.