Design,Synthesis, and Evaluation of WC5 Analogues as Inhibitors of Human Cytomegalovirus Immediate‐Early 2 Protein,a Promising Target for Anti‐HCMV Treatment

Although human cytomegalovirus (HCMV) infection is mostly asymptomatic for immunocompetent individuals, it remains a serious threat for those who are immunocompromised, in whom it is associated with various clinical manifestations. The therapeutic utility of the few available anti‐HCMV drugs is limited by several drawbacks, including cross‐resistance due to their common mechanism of action, i.e., inhibition of viral DNA polymerase. Therefore, compounds that target other essential viral events could overcome this problem. One example of this is the 6‐aminoquinolone WC5 , which acts by directly blocking the transactivation of essential viral Early genes by the Immediate‐Early 2 (IE2) protein. In this study, the quinolone scaffold of the lead compound WC5 was investigated in depth, defining more suitable substituents for each of the scaffold positions explored and identifying novel, potent and nontoxic compounds. Some compounds showed potent anti‐HCMV activity by interfering with IE2‐dependent viral E gene expression. Among them, naphthyridone 1 was also endowed with potent anti‐HIV activity in latently infected cells. Their antiviral profile along with their innovative mechanism of action make these anti‐HCMV quinolones a very promising class of compounds to be exploited for more effective antiviral therapeutic treatment.     

Laboratory creping equipment

Tissue production is largely dependent on the creping process as creping influences the paper properties and thus the quality of the end product and the runnability of the tissue machine. The process is very complex and includes numerous variables affecting the adhesion, and ultimately the creping of the tissue paper. To perform experiments on a full-scale machine, or even on a pilot machine, is very costly; therefore, a laboratory scale creping device is demanded, able to replicate conditions encountered on a tissue machine. In this paper, new laboratory testing equipment is developed, whereby the adhesion between paper and metal surfaces (when scraping off the paper with configurations similar to the industrial process) can be studied. A new method to adhere paper to metal, used in the new laboratory creping equipment, is also developed. To evaluate the equipment, different creping angles were tested. The scraping tests show a trend in decreasing creping force for an increasing creping angle.     

Influence of textile treatment on mechanical and sorption properties of flax/epoxy composites

The aim of the present work is to study the effect of conventional textile treatments of woven flax on the mechanical properties and the water sorption of flax/epoxy composites. The flax fabrics are standard 2/2 twills. Various treatments are carried out on fabric such as mercerization, bleaching, and leaching for long fibers or on yarn such as leaching for short fibers. A model, based on a modified rule of mixture applied to composite reinforced with woven fabric, is developed to include the effect of fiber and porosity volume fractions on composite stiffness and strength. Most treatments improve tensile stiffness and strength of flax/epoxy composite and reduce composite water sorption. We prove by X‐ray fluorescence analysis, thermogravimetric analysis, and tensile tests of dry fabric that it is due to an improvement in the interfacial bonding between fibers and matrix. The best performances are achieved with bleaching and mercerization treatment. The weakest performances are obtained with the composites made with leached yarns. POLYM. COMPOS., 34:1761–1773, 2013. © 2013 Society of Plastics Engineers     

Cytostatic activity of 1,10-phenanthroline derivatives generated by the clip-phen strategy

The cytostatic activities of a series of twelve 1,10-phenanthroline (Phen) derivatives and of their copper complexes were studied on L1210 murine leukemia cells. Large increases in the biological activity were observed for compounds of the 3-Clip-Phen series, in which two Phen moieties were bridged at their C3 positions by an alkoxy linker, the 3-pentyl-Clip-Phen derivative showing an IC(50) value of 130 nM while Phen shows an IC(50) value of 2500 nM under the same conditions. IC(50) values seemed to be modulated not only by the position, the nature, and the length of the linker of Clip-Phen but also by hydrophobicity. Since copper complexes of Phen are chemical nucleases and nucleic acids are thus a potential target for these compounds, the corresponding copper complexes were also studied. Copper complexation of the 3-Clip-Phen ligands did not increase their biological activities. Attempts to vectorize 3-Clip-Phen derivatives with a DNA binder such as spermine or with a cell-penetration peptide failed to increase their biological activity relative to the original 3-Clip-Phen series.     

Modeling bread baking with focus on overall deformation and local porosity evolution

A two dimensional model of bread baking was developed including, for the first time, the dependence of dough viscosity on both temperature and moisture content, the carbon dioxide dissolved from liquid water together with gas generation from yeast at the beginning of baking and the shrinkage due to dough drying. Particular attention was paid to experimental validation of both overall and local variables such as local temperature, overall mass loss, and local moisture content, overall CO₂ released into the oven, and overall deformation and local expansion or shrinkage. Sensitivity studies on generation of carbon dioxide, gravity, and shrinkage are presented to discuss their influences on bread geometry, porosity (reflecting the alveolar structure) and gas pressure. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3847–3863, 2016     

Kinetics of Multi‐Step Redox Processes by Time‐Resolved In Situ X‐ray Diffraction

The kinetics of redox reactions of iron oxide in oxygen carrier 50Fe₂O₃/MgAl₂O₄ are examined using different time‐resolved techniques. Reduction kinetics are studied by H₂ temperature‐programmed reduction (H₂‐TPR) monitored by time‐resolved in situ XRD. In contrast to conventional TPR, in situ XRD distinguishes the three‐stage reduction of Fe₂O₃ → Fe₃O₄ → FeO → Fe. It also shows that the oxidation of Fe → Fe₃O₄ by CO₂ has no intermediate crystalline phases, explaining why its kinetics can easily be investigated by conventional CO₂ temperature‐programmed oxidation (CO₂‐TPO). A shrinking core model which takes into account solid state diffusion allows describing the experimental data.     

The P2Y2 Receptor C-Terminal Tail Modulates but Is Dispensable for β-Arrestin Recruitment

The P2Y₂ receptor (P2Y₂R) is a G protein-coupled receptor that is activated by extracellular ATP and UTP, to a similar extent. This allows it to play roles in the cell’s response to the (increased) release of these nucleotides, e.g., in response to stress situations, including mechanical stress and oxygen deprivation. However, despite its involvement in important (patho)physiological processes, the intracellular signaling induced by the P2Y₂R remains incompletely described. Therefore, this study implemented a NanoBiT^® functional complementation assay to shed more light on the recruitment of β-arrestins (βarr1 and βarr2) upon receptor activation. More specifically, upon determination of the optimal configuration in this assay system, the effect of different (receptor) residues/regions on βarr recruitment to the receptor in response to ATP or UTP was estimated. To this end, the linker was shortened, the C-terminal tail was truncated, and phosphorylatable residues in the third intracellular loop of the receptor were mutated, in either singly or multiply adapted constructs. The results showed that none of the introduced adaptations entirely abolished the recruitment of either βarr, although EC₅₀ values differed and time-luminescence profiles appeared to be qualitatively altered. The results hint at the C-terminal tail modulating the interaction with βarr, while not being indispensable.