Improvement of Aglycone π-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists

Antimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl α-d -mannosides leads to compounds with perfect π–π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar K_D values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as ¹H,¹⁵N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability.     

Flow behavior in a corotating twin‐screw extruder of pure polymers and blends: Characterization by fluorescence monitoring technique

The objective of this work was to investigate the flow behavior of pure polymers and blends, especially miscible polymer/polymer systems, in a corotating twin‐screw extruder (TSE) using an online fluorescence monitoring device. An immiscible blend was also studied for the sake of comparison. The fluorescence signal was obtained by using synthesized fluorescence tracers added to the melt at very low concentrations. These tracers consisted of two styrene‐maleic anhydride copolymers (SMA) labeled with anthracene. The investigated blends were SMA8 (8 wt % of MA in SMA)/polystyrene (PS), SMA14 (14 wt % of MA in SMA)/styrene acrylonitrile copolymer (SAN), and poly(methyl methacrylate) (PMMA)/ethyl acrylate‐methyl methacrylate copolymer (PMMAEA). The residence time distribution (RTD), the mean residence time (t ), the dimensionless variance (σ_θ²), the Peclet number (Pe) and the fluorescence peak intensity distribution of pure polymers and binary polymer systems were investigated and interpreted in terms of polymers rheological properties. It was observed that polymers presenting higher viscosity or higher pressure showed longer residence time. A difference in behavior was also observed for the RTD of miscible and immiscible blends. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

LAMINAR FREE CONVECTION IN VERTICAL AIR-FILLED CAVITIES WITH MIXED BOUNDARY CONDITIONS

A numerical investigation was conducted on the two-dimensional laminar free convection within rectangular cavities having mixed boundary conditions on the vertical surfaces and adiabatic top and bottom walls. The time-dependent governing energy, vorticity and stream function equations were solved using a modified ADI method and Gauss-Seidel SOR. Steady state solutions for air (Pr ≈ 0.7) were obtained for cavity aspect ratios of 0.5 to 15 over a modified Rayleigh number range of 690 to 1.3 × 10₅. For a given heat flux, it was found that the average Nusselt number peaked at an aspect ratio of about 1.5. The boundary between the asymptotic and laminar boundary layer regimes also showed a reversing behaviour in this region. In general, the reported results are compatible with and form an extension to the limited numerical and experimental results of previous investigators.     

Bioactive and Physicochemical Properties of Persimmon as Affected by Drying Methods

In this study, the effects of three different drying methods (freeze drying, oven drying, and vacuum oven drying) on bioactive (total phenolics, total flavonoids, condensed tannin and total hydrolyzable tannin contents, antiradical activity, and antidiabetic activity) and some physicochemical (dry matter, ash, water activity (a _w ), color, protein, hydroxymethylfurfural, glucose and fructose content) properties of persimmon fruit were investigated. Simplex lattice mixture design methodology was applied to determine the best solvent mixture for the extraction of phenolics from the samples. It was found that the mixture of acetone:water at the ratio of 50:50 % (v/v) was the best solvent mixture for the extraction. The persimmon powder sample obtained from freeze drying showed significantly (p <0.05) higher bioactivity values than oven- and vacuum-oven-dried samples. Antiradical activity changed significantly depending on the drying method employed and it was superior in freeze-dried samples than that of the other drying methods.     

Development of a fluidized bed thermogravimetric analyzer

A new fluidized bed thermogravimetric analyzer (FB‐TGA) was developed that introduces two major particularities: the pseudo variation of the weight of the reactor and the special strategy for gas flow rate adjustment according to temperature. A momentum balance was performed on the reactor and the pseudo variation of the reactor weight was evaluated by measuring the pressure drop through the gas distributor and filter. The real weight loss of the reactor was obtained by subtracting the pseudo variation of the weight from the total weight loss measured by the load cell. In addition, a special program for the gas flow rate as a function of temperature was developed and used; so the minimum fluidization regime is maintained throughout all of the experiments. The validation test of the FB‐TGA was carried out on calcium hydroxide decomposition, and the results were compared with those obtained from the conventional TGA. Diffusion control was suppressed by the application of the FB‐TGA, which was confirmed by the x‐ray diffraction analysis on the treated samples. © 2014 American Institute of Chemical Engineers AIChE J, 61: 84–89, 2015     

Optimal Sizing of a DBD Ozone Generator Using Response Surface Modeling

Dielectric barrier discharge (DBD) reactors used as ozone generators are well known today and widely used for water treatment and air disinfection. The purpose of this article is to propose an experimental procedure based on the response surface modeling in order to optimize the geometrical dimensions of the cylindrical shape ozone generator, i.e., the discharge gap and the electrodes length. Because an effective ozone generator is expected to give high ozone concentration with a minimum of power requirements, the applied high voltage was associated with the geometrical parameters to carry out a composite centered faces design. Obtained results indicate that for an efficient ozone generator, length of the electrodes needs to be optimized while the discharge gap should be minimized.     

Microbial Fuel Cell Application for Azoic Dye Decolorization with Simultaneous Bioenergy Production Using Stenotrophomonas sp.

A single‐chamber air‐cathode microbial fuel cell (MFC) was successfully applied for decolorization of the diazoic dye Reactive Black 5 (RB5) with simultaneous production of electricity. An innovative low‐cost medium, the marine water‐glucose‐yeast extract medium (MWGY), was developed which appears as a textile marine effluent in terms of salinity. The anode compartment containing a single bacterial strain of Stenotrophomonas sp. showed almost complete dye decolorization with different RB5 concentrations after seven days of treatment. For the four dye concentrations used, a correlation between dye removal and production of electrical energy was found. The comparison of the decolorization process in the MFC with that in a batch reactor as control experiment highlights the efficiency of the single‐chamber air‐cathode MFC technology which improved the dye removal by the same bacterial strain.     

The Tyrosine Gate of the Bacterial Lectin FimH: A Conformational Analysis by NMR Spectroscopy and X‐ray Crystallography

Urinary tract infections caused by uropathogenic E. coli are among the most prevalent infectious diseases. The mannose‐specific lectin FimH mediates the adhesion of the bacteria to the urothelium, thus enabling host cell invasion and recurrent infections. An attractive alternative to antibiotic treatment is the development of FimH antagonists that mimic the physiological ligand. A large variety of candidate drugs have been developed and characterized by means of in vitro studies and animal models. Here we present the X‐ray co‐crystal structures of FimH with members of four antagonist classes. In three of these cases no structural data had previously been available. We used NMR spectroscopy to characterize FimH–antagonist interactions further by chemical shift perturbation. The analysis allowed a clear determination of the conformation of the tyrosine gate motif that is crucial for the interaction with aglycone moieties and was not obvious from X‐ray structural data alone. Finally, ITC experiments provided insight into the thermodynamics of antagonist binding. In conjunction with the structural information from X‐ray and NMR experiments the results provide a mechanism for the often‐observed enthalpy–entropy compensation of FimH antagonists that plays a role in fine‐tuning of the interaction.     

A study on the properties of PMMA/silica nanocomposites prepared via RAFT polymerization

A number of batch polymerizations were performed to study the effect of pristine nanoparticle loading on the properties of PMMA/silica nanocomposites prepared via RAFT polymerization. In order to improve the dispersion of silica nanoparticles in PMMA matrix, the silanol groups of the silica are functionalized with methyl methacrylate groups and modified nanoparticles were used to synthesize PMMA/modified silica nanocomposites via RAFT polymerization. Prepared samples were characterized by thermogravimetric analysis (TGA), dynamic light scattering (DLS), dynamic mechanical thermal analysis (DMTA), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). According to results, introduction of modified nanoparticles results in better thermal and mechanical properties than those of pristine nanoparticles. Also, surface modification and increasing silica nanoparticles result in variation of thermal degradation behavior of nanocomposites. The best improvement of mechanical and thermophysical properties is achieved for nanocomposites containing 7 wt. % silica nanoparticles.