Conformational Stabilization of Gp41-Mimetic Miniproteins Opens Up New Ways of Inhibiting HIV-1 Fusion

Inhibition of the HIV-1 fusion process constitutes a promising strategy to neutralize the virus at an early stage before it enters the cell. In this process, the envelope glycoprotein (Env) plays a central role by promoting membrane fusion. We previously identified a vulnerability at the flexible C-terminal end of the gp41 C-terminal heptad repeat (CHR) region to inhibition by a single-chain miniprotein (named covNHR-N) that mimics the first half of the gp41 N-terminal heptad repeat (NHR). The miniprotein exhibited low stability, moderate binding to its complementary CHR region, both as an isolated peptide and in native trimeric Envs, and low inhibitory activity against a panel of pseudoviruses. The addition of a disulfide bond stabilizing the miniprotein increased its inhibitory activity, without altering the binding affinity. Here, to further study the effect of conformational stability on binding and inhibitory potency, we additionally stabilized these miniproteins by engineering a second disulfide bond stapling their N-terminal end, The new disulfide-bond strongly stabilizes the protein, increases binding affinity for the CHR target and strongly improves inhibitory activity against several HIV-1 strains. Moreover, high inhibitory activity could be achieved without targeting the preserved hydrophobic pocket motif of gp41. These results may have implications in the discovery of new strategies to inhibit HIV targeting the gp41 CHR region.     

Extraction and Characterization of Montmorency Sour Cherry (Prunus cerasus L.) Pit Oil

Montmorency sour cherry (Prunus cerasus L.) pit oil (CPO) was extracted and characterized by various methods including: GC, LC–MS, NMR, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and X‐ray powder diffraction (XRD). The oil gave an acid value of 1.45 mg KOH/g, saponification value of 193 mg KOH/g and unsaponifiable matter content of 0.72 %. The oil contained oleic (O) and linoleic (l ) acids as the major components with small concentrations of α‐eleostearic acid (El, 9Z,11E,13E‐octadecatrienoic acid) and saturated fatty acid palmitic (P) acid. The CPO contained six major triacyglycerols (TAG), OOO (16.83 %), OLO (16.64 %), LLO (13.20 %), OLP (7.25 %), OOP (6.49 %) and LElL (6.16 %) plus a number of other minor TAG. The TAG containing at least one saturated fatty acid constitute 33 % of the total. The polymorphic behavior of CPO as studied by DSC and XRD confirmed the presence of α, β′ and β crystal forms. The oxidative induction time of CPO was 30.3 min at 130 °C and the thermal decomposition temperature was 352 °C.     

Novel nucleophilic/basic and acidic organocatalysts for reaction between poorly reactive diisocyanate and diols

Original basic or acidic organic compounds derived from guanidine or phenyl phosphonic acid were specifically designed and tested as new catalysts for the bulk synthesis of polyurethane prepolymers from a precursor system with particularly low reactivity (secondary alcohol + aliphatic isocyanate at low temperature). Both families showed interesting catalytic activities at 60–80 °C, but must nevertheless be used in much higher amounts (1 mol%, i.e. between 0.15 and 0.50 wt%) than traditional metal-based catalysts. The efficiency of guanidine derivatives seems to be related to their nucleophilicity, whereas that of phosphonic acid derivatives depends on their acidity. However, the solubility of the considered species in the reactive medium also plays a major role. The water/alcohol selectivity of the catalysts, especially at room temperature, was then examined as an additional criterion. Guanidines are not selective and favor the reaction of isocyanate groups with water as much as that with alcohols. Phenyl phosphonic acid derivatives are more selective, and particularly pentafluorophenyl phosphonic acid displays a remarkable catalytic activity together with an acceptable selectivity and could represent an interesting and safer alternative to toxic tin and mercury derivatives for many industrial polyurethanes.     

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     

BaTiO3 incorporation effect on the dielectric properties of polymer from aqueous emulsion: An enhanced dispersion technique

An economic and environment friendly process was adapted to synthesize new dielectric composite materials. Using ethylene vinyl acetate (EVA)/vinyl ester of versatic acid (VeoVa) terpolymer as an aqueous emulsion provides a homogenous dispersion of BaTiO₃ (BT) particles, due to the high viscosity and polarity of the vinyl resin (VR). Composites films were obtained from these dispersions by water evaporation. The evolution of the dielectric properties as a function of the BaTiO₃ content, was correctly fitted by a Maxwell‐Garnett model. This fitting of the experimental curve shows a good dispersion of filler in the vinyl resin and the particles separation by a layer of resin as expected for the preparation method used in this study. The VR/BT composites show good synergy between the dielectric properties of the different phases of the composites due to the formation of macrodipoles and to the strong interactions between polar EVA/VeoVa groups and the BaTiO₃ particles surface. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44333.     

Sol–Gel-Prepared Pure and Lithium-Doped Hexacelsian Polymorphs: An Infrared, Raman, and Thermal Expansion Study of the β-Phase Stabilization by Frozen Short-Range Disorder

Monoclinic and hexagonal forms of celsians (BaAl₂Si₂O₈) were synthesized by hydrolysis–polycondensation of Si/Al alkoxide mixtures. Dilatometry, Raman scattering, IR absorption, and X-ray diffraction techniques were used to identify various hexacelsian phases and their conversion into the monoclinic phase as a function of thermal treatments and doping. Emphasis is given to the relationship between the shrinkage behavior and the static and dynamic short-range disorders in the XO₄ tetrahedra (X = Si/Al) arrangement. The α hexagonal phase exhibits a well-defined α–β_HT transition at about 300°C but a statically disorderedβ_SD form, which does not vary very much with temperature and is very similar to the β_HT form obtained below 300°C for some materials. This statically disordered phase is preferentially observed for fast-sintered lithium-free compositions and transforms gradually in the ordered form by annealing above 1100°C. Such stabilization of the high-temperature phase by the static disorder arising from the peculiar synthesis through alkoxide hydrolysis and the gel route, which freeze the dynamic disorder of gel-forming entities in a static disorder at the gelation step, is discussed in the light of previously observed cases. The thermal expansion behavior is very sensitive to the synthesis conditions, doping, and thermal treatments. The ordered α phase is more easily achieved with lithium-doped compositions, but lithium addition shifts the hexagonal-to-monoclinic phase transformation onset toward lower temperatures and promotes complete transformation with thermal annealing.     

Production of Biomass-Derived Chemicals and Energy: Chemocatalytic Conversions of Glycerol

The growing production of biodiesel as a renewable source-based fuel leads to an increased amount of glycerol. Thus, it is a favorable starting material to obtain highly functionalized products. From a variety of catalytic reactions three examples, namely glycerol oxidation, glycerol hydrogenolysis and aqueous-phase reforming, were chosen for detailed studies in our group. The experimental focus for the oxidation of glycerol was set on preparation and detailed examination of supported Pt–Bi catalysts in batch reactions as well as in continuous experiments using a trickle bed reactor. For aqueous-phase reforming of glycerol to hydrogen the addition of tin to supported platinum catalysts was investigated. Ruthenium and copper based catalysts could be successfully applied in the hydrogenolysis of glycerol to 1,2-propanediol.     

A scientific application oriented classification for metal transfer modes in GMA welding

In this work, metal transfer in solid wire GMA welding was studied. Several experiments with different combinations of gas-wire-parameters were carried out to observe metal transfer and to characterize the various transfer modes. A laser shadograph system with synchronized electrical signals and high speed filming were used. New modes were observed and their particular characteristics described for completeness. A classification for metal transfer, oriented to scientific personnel (researchers, scholars and students), is proposed, in which the modes are independent of the type of shielding gas or welding power source.     

Joint strength optimization by the mixed-adhesive technique

An ideal adhesive lap joint is one in which the adhesive flexibility and strength properties vary along the overlap length. Because of greater adhesive shear strains at the edges of the overlap, a ductile and flexible adhesive should be used at the overlap ends, while in the middle a stiff and less-ductile adhesive should be used. This technique has been investigated in the past but only a few studies have reported any experimental evidence. In the present study, single-lap adhesive joints were manufactured and tested maintaining the same brittle adhesive in the middle of the overlap and using three different ductile adhesives of increasing ductility at the ends of the overlap. A simple joint strength prediction is proposed for mixed-adhesive joints. The mixed-adhesive technique gives joint strength improvements in relation to a brittle adhesive alone in all cases. For a mixed adhesive joint to be stronger than the brittle adhesive and the ductile adhesive used individually, the load carried by the brittle adhesive must be higher than that carried by the ductile adhesive.