Pharmacomodulation of a ligand targeting the HBV capsid hydrophobic pocket

Hepatitis B virus (HBV) is a small enveloped retrotranscribing DNA virus and an important human pathogen. Its capsid-forming core protein (Cp) features a hydrophobic pocket proposed to be central notably in capsid envelopment. Indeed, mutations in and around this pocket can profoundly modulate, and even abolish, secretion of enveloped virions. We have recently shown that Triton X-100, a detergent used during Cp purification, binds to the hydrophobic pocket with micromolar affinity. We here performed pharmacomodulation of pocket binders through systematic modifications of the three distinct chemical moieties composing the Triton X-100 molecule. Using NMR and ITC, we found that the flat aromatic moiety is essential for binding, while the number of atoms of the aliphatic chain modulates binding affinity. The hydrophilic tail, in contrast, is highly tolerant to changes in both length and type. Our data provide essential information for designing a new class of HBV antivirals targeting capsid–envelope interactions.

Small-molecule binding to the Hepatitis B virus core protein hydrophobic pocket, a possible strategy for targeting viral particle assembly.     

Flexible active matrix addressed displays manufactured by printing and coating techniques

A flexible electrochromic active matrix addressed display, including 8 × 8 pixels, is demonstrated by using solution processing based on standard printing and coating manufacturing techniques. Each organic electrochromic display (OECD) pixel and its corresponding organic electrochemical transistor (OECT) are located on different sides of the flexible PET substrate. Electronic vias generated through the plastic substrate connects each OECD pixel with one addressing OECT. When comparing this display with actively addressed OECDs with all its components located on the same side, the present approach based on this electronic via substrate provides an enhanced pixel resolution and a relatively more simplified manufacturing process. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2-diones,pyrrolo[3,2,1-ij]quinoline-1,2-diones and other polycyclic isatin derivatives

To further expand the structure–cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC₅₀ 3.01 μM) after 24 h.     

Transformation of macromonomers into ring‐opening polymerization macroinitiators: A detailed initiation efficiency study

In the present study, n‐butyl acrylate macromonomer (BAMM) (M_n = 1900 g mol^?1; PDI = 1.96) has been synthesized via a high‐temperature polymerization process. Subsequently, the olefinic termini of the BAMM have been transformed into a diol via a dihydroxylation process using KMnO₄ as an oxidizing agent. The OH‐terminated macroinitiator pBA(OH)₂ has subsequently been employed for the ring‐opening polymerization (ROP) of ε‐caprolactone via various catalytic systems, that is, organo‐(1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene), metal (tin(II) 2‐ethylhexanoate), and enzymatic catalysis (Novozym® 435). The obtained pBA‐b‐pCL block copolymers and the initiation efficiency of the BAMM macroinitiator have been investigated via size exclusion chromatography (SEC), electrospray ionization–mass spectrometry (ESI‐MS) hyphenated with SEC and liquid chromatography at the critical conditions of both poly(ε‐caprolactone) (pCL) and pBA. The in vitro enzyme catalysis (eROP) approach proved to be the most efficient catalysis system due to minor transesterification side reactions during the polymerization process. However, side reactions such as transesterifications occur in each catalytic system and—while they cannot be suppressed—they can be minimized. The species generated during the eROP process include the desired block copolymer pBA‐b‐pCL as main species as well as pCL homopolymer and residual macroinitiator pBA(OH)₂. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

High-power laser with Nd:YAG single-crystal fiber grown by the micro-pulling-down technique

We present optical characterization and laser results achieved with single-crystal fibers directly grown by the micro-pulling-down technique. We investigate the spectroscopic and optical quality of the fiber, and we present the first laser results. We achieved a cw laser power of 10 W at 1064 nm for an incident pump power of 60 W at 808 nm and 360 kW peak power for 12 ns pulses at 1 kHz in the Q-switched regime. It is, to the best of our knowledge, the highest laser power ever achieved with directly grown single-crystal fibers.     

Nonlinear resonant ultrasound spectroscopy (NRUS) applied to damage assessment in bone

Nonlinear resonant ultrasound spectroscopy (NRUS) is a resonance-based technique exploiting the significant nonlinear behavior of damaged materials. In NRUS, the resonant frequency(ies) of an object is studied as a function of the excitation level. As the excitation level increases, the elastic nonlinearity is manifest by a shift in the resonance frequency. This study shows the feasibility of this technique for application to damage assessment in bone. Two samples of bovine cortical bone were subjected to progressive damage induced by application of mechanical cycling. Before cycling commenced, and at each step in the cycling process, NRUS was applied for damage assessment. For independent assessment of damage, high-energy x-ray computed tomography imaging was performed but was only useful in identifying the prominent cracks. As the integral quantity of damage increased, NRUS revealed a corresponding increase in the nonlinear response. The measured change in nonlinear response is much more sensitive than the change in linear modulus. The results suggest that NRUS could be a potential tool for micro-damage assessment in bone. Further work must be carried out for a better understanding of the physical nature of damaged bone and for the ultimate goal of the challenging in vivo implementation of the technique.     

Contribution a L'etude de melanges susceptibles de former des microemulsions selon leurs compositions,par la definition de leurs comportements dielectriques a 9,455 GHz

The dielectric studies of four components mixtures are rarely made on a great deal of concentrations. The authors propose a dielectric behavior study of mixtures made with toluene-water-butanol-SDS, from specific mappings of permittivities which are plotted on pseudo ternary diagrams at 9.455 GHz. They draw different conclusions to know how at 9.455 GHz the variations of real and imaginary parts of permittivity involve the concentration of each component and the structure of the mixture.These conclusions will be perfected by studies made at other frequencies and by spectral analysis of each mixture.     

Effect of high pressure processing on the preservation of frozen and re-thawed sliced cod (Gadus morhua) and salmon (Salmo salar) fillets

Cod and salmon are both widely found in the seafood market, but those products are easily spoiled. This work reports on the investigation of the effects of three moderate pressure values (150, 300 and 450?MPa) applied for 5?min at 20°C on crude sliced cod and salmon fillets. It was found that high pressure processing (HPP) significantly reduced the microbial load during refrigerated storage for up to 14 days. As expected, the most effective treatment was 450?MPa because it inhibited microbial growth. This process affected the hardness, lightness, lipid oxidation, protein denaturation and oxidation. The fish muscle composition (lipid amount and protein profile) played a main role in the changes promoted by pressure. HPP permits the shelf life of the raw product at 4°C to be increased with minimal changes in the organoleptic characteristics and to enable crude consumption.