Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Analysis of bacterial diversity in river biofilms using 16S rDNA PCR-DGGE: methodological settings and fingerprints interpretation

Reliability of bacterial diversity assessment using polymerase chain reaction (PCR) denaturing gradient gel electrophoresis (DGGE) analysis of 16S rDNA fragments was evaluated for a particular complex microbial assemblage: river epilithic biofilm. By comparing 3 routine protocols on replicates of one river biofilm sample, we found that common DNA extraction procedures gave comparable diversity (from 28.0 to 30.7 bands detected) and community composition (> 75% of homology) despite differences in the total amount of extracted DNA (from 0.9 to 4.2 microg). Therefore methodological improvements only concerned electrophoretic separation of DNA fragments (range of denaturing gradient from 35% to 70% and migration time=18h) and standardisation of DNA amounts used (PCR-template=50 ng, gel loading=700 ng). Using such a standardised methodology we found a good reproducibility of all steps of the procedure. When an Escherichia coli strain was introduced as a contaminant in a biofilm sample, we were able to recover ribotypes from the strain. As concerns fields sampling, a satisfactory repeatability of banding patterns from neighbouring pebbles (sampling point) allowed discriminating between the biofilm intrasite variability (various points from a cross-profile). These trials confirmed that PCR-DGGE is suitable to assess a reliable genetic fingerprint of epilithic biofilms in the river. Phylogenetic analysis of 40 partial sequences of 16S rDNA from DGGE gels of two sets of river biofilms samples proved evidences for the retrieval of DNA fragments related to phototroph Eukarya. However, in both cases plastidial 16S rDNA represented less than 25% of the analysed operational taxonomic units. Taking into account that Cyanobacteria, as members of the Bacteria, were also detected, sequence analysis of relevant bands from the pattern is required to target "bacteria", i.e. the functional group of prokaryotic microorganisms to which one commonly refers as a key component in sustaining the nutrient turnover.     

45S5 bioactive glass coatings by atmospheric plasma spraying obtained from feedstocks prepared by different routes

45S5 bioactive glass powders with the composition of 45 SiO₂, 6 P₂O₅, 24.5 CaO and 24.5 wt% Na₂O were melted and quenched in water to obtain a frit. The frit was milled using two different routes: dry milling followed by sieving to obtain glass particles and wet milling followed by spray drying to obtain a powder comprising porous agglomerates. All feedstocks showed adequate characteristics that make them suitable to be deposited by atmospheric plasma spraying. The powders and coatings were characterised by field-emission gun environmental scanning electron microscope and X-ray diffraction. The roughness and the contact angle of the coatings were also determined. The bioactivity of the powders and coatings was assessed by immersion in simulated body fluid. It was found that bioactive glass prepared from bioglass frit by dry milling exhibited similar bioactivity as that of a commercial bioactive glass. All coatings produced showed good adhesion to the substrate as well as suitable surface properties to ensure efficient contact with body fluid. Regardless of the characteristics of the feedstocks or plasma spray conditions used, all coatings were exclusively made up of an amorphous phase. On the other hand, micrographs revealed that the characteristics of the feedstock strongly impact on the final coating microstructure. The most homogeneous microstructure was obtained when the feedstock was prepared by fine dry grinding of the frit. For this coating, the formation of a bioactive layer was also proved by Fourier transform infrared spectroscopy and X-ray diffraction.     

Power MOSFET quality and robustness enhancement with a new QBD characterization performed at probe–die–wafer level

The quality of the gate oxide is a central parameter for power MOSFET devices dedicated to automotive applications. Reliability is systematically evaluated through electrical tests. The purpose of this study is to apply the Q_BD test directly at probe–die–wafer level and to correlate its results with reliability test conclusions. In other words, this new kind of Q_BD test is a monitor of power MOSFET robustness which helps identify extrinsic failures and the process steps responsible. In summary, it is an accurate and fast measurement method of identifying weakened parts and enhancing device quality.     

Plasmonic near-electric field enhancement effects in ultrafast photoelectron emission: correlated spatial and laser polarization microscopy studies of individual ag nanocubes

Electron emission from single, supported Ag nanocubes excited with ultrafast laser pulses (λ = 800 nm) is studied via spatial and polarization correlated (i) dark field scattering microscopy (DFM), (ii) scanning photoionization microscopy (SPIM), and (iii) high-resolution transmission electron microscopy (HRTEM). Laser-induced electron emission is found to peak for laser polarization aligned with cube diagonals, suggesting the critical influence of plasmonic near-field enhancement of the incident electric field on the overall electron yield. For laser pulses with photon energy below the metal work function, coherent multiphoton photoelectron emission (MPPE) is identified as the most probable mechanism responsible for electron emission from Ag nanocubes and likely metal nanoparticles/surfaces in general.     

A restoration framework for ultrasonic tissue characterization

Ultrasonic tissue characterization has become an area of intensive research. This procedure generally relies on the analysis of the unprocessed echo signal. Because the ultrasound echo is degraded by the non-ideal system point spread function, a deconvolution step could be employed to provide an estimate of the tissue response that could then be exploited for a more accurate characterization. In medical ultrasound, deconvolution is commonly used to increase diagnostic reliability of ultrasound images by improving their contrast and resolution. Most successful algorithms address deconvolution in a maximum a posteriori estimation framework; this typically leads to the solution of l(2)-norm or (1)-norm constrained optimization problems, depending on the choice of the prior distribution. Although these techniques are sufficient to obtain relevant image visual quality improvements, the obtained reflectivity estimates are, however, not appropriate for classification purposes. In this context, we introduce in this paper a maximum a posteriori deconvolution framework expressly derived to improve tissue characterization. The algorithm overcomes limitations associated with standard techniques by using a nonstandard prior model for the tissue response. We present an evaluation of the algorithm performance using both computer simulations and tissue-mimicking phantoms. These studies reveal increased accuracy in the characterization of media with different properties. A comparison with state-of-the-art Wiener and l(1)-norm deconvolution techniques attests to the superiority of the proposed algorithm.