Dynamic mechanical spectrometry for the study of multiphase polymer materials

The dynamic mechanical behaviour of multiphase polymer materials depends on two factors: (i) properties of each phase and (ii) geometric arrangement of these phases (so-called morphology). Analysis of experimental results has been performed in order to separate these two factors; it leads to informations about morphology, presence of interphase between main phases, chemical composition of different domains and possible changes in physical properties of one phase, induced by its neighbours. The interest in such an analysis based on mechanical spectrometry appears important because of difficulties in direct investigations (low contrast in Electron Microscopy, poor information provided by X-ray measurements on amorphous polymers … )     

Physical model explaining the effect of physical ageing on dynamic mechanical and calorimetric properties of poly(methyl methacrylate)

Using the theory of non-elastic deformation based on a specific model for the mobility in amorphous polymers, an equation was obtained including the real and imaginary parts of the complex modulus and the heat capacity as a function of temperature and ageing time. Thus, the model is based on the calculation of time and temperature evolution of the population of “faults” (corresponding to an excess of enthalpy and entropy) in the structure. We employ the model with only one “characteristic” relaxation time obtained from a concept of hierarchical correlation. The parameters appearing in the equations for G* and c_p are the same in each case and are obtained from classical experiments (mechanical spectroscopy, dilatometry, calorimetry, etc.), thus having a specific physical meaning. Dynamic loss tangent and specific heat of PMMA measured after different thermal histories involving isothermal ageing agrees quite well with the prediction of the model.     

Effect of ions on a dipalmitoyl phosphatidylcholine bilayer. a molecular dynamics simulation study

The effect of physiological concentrations of different chlorides on the structure of a dipalmitoyl phosphatidylcholine (DPPC) bilayer has been investigated through atomistic molecular dynamics simulations. These calculations provide support to the concept that Li+, Na+, Ca2+, Mg2+, Sr2+, Ba2+, and Ac3+, but not K+, bind to the lipid-head oxygens. Ion binding exhibits an influence on lipid order, area per lipid, orientation of the lipid head dipole, the charge distribution in the system, and therefore the electrostatic potential across the head-group region of the bilayer. These structural effects are sensitive to the specific characteristics of each cation, i.e., radius, charge, and coordination properties. These results provide evidence aimed at shedding some light into the apparent contradictions among different studies reported recently regarding the ordering effect of ions on zwitterionic phosphatidylcholine lipid bilayers.     

Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial–mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface liquid layer facilitating microbial colonization and inflammation. The SERPINA1 gene, encoding alpha1-antitrypsin (AAT) protein, is one of the genes implicated in CF, however it remains unknown whether AAT has any influence on CFTR levels. In this study we assessed CFTR protein levels in primary human lung epithelial cells grown at the air-liquid-interface (ALI) alone or pre-incubated with AAT by Western blots and immunohistochemistry. Histological analysis of ALI inserts revealed CFTR- and AAT-positive cells but no AAT-CFTR co-localization. When 0.5 mg/mL of AAT was added to apical or basolateral compartments of pro-inflammatory activated ALI cultures, CFTR levels increased relative to activated ALIs. This finding suggests that AAT is CFTR-modulating protein, albeit its effects may depend on the concentration and the route of administration. Human lung epithelial ALI cultures provide a useful tool for studies in detail how AAT or other pharmaceuticals affect the levels and activity of CFTR.     

Design and optimization of a fused‐silica microfluidic device for separation of trivalent lanthanides by isotachophoresis

Elemental analysis of rare earth elements is essential in a variety of fields including environmental monitoring and nuclear safeguards; however, current techniques are often labor intensive, time consuming, and/or costly to perform. The difficulty arises in preparing samples, which requires separating the chemically and physically similar lanthanides. However, by transitioning these separations to the microscale, the speed, cost, and simplicity of sample preparation can be drastically improved. Here, all fourteen non‐radioactive lanthanides (lanthanum through lutetium minus promethium) are separated by ITP for the first time in a serpentine fused‐silica microchannel (70 µm wide × 70 µm tall × 33 cm long) in <10 min at voltages ≤8 kV with limits of detection on the order of picomoles. This time includes the 2 min electrokinetic injection time at 2 kV to load sample into the microchannel. The final leading electrolyte consisted of 10 mM ammonium acetate, 7 mM α‐hydroxyisobutyric acid, 1% polyvinylpyrrolidone, and the final terminating electrolyte consisted of 10 mM acetic acid, 7 mM α‐hydroxyisobutyric acid, and 1% polyvinylpyrrolidone. Electrophoretic electrodes are embedded in the microchip reservoirs so that voltages can be quickly applied and switched during operation. The limits of detection are quantified using a commercial capacitively coupled contactless conductivity detector (C⁴D) to calculate ITP zone lengths in combination with ITP theory. Optimization of experimental procedures and reproducibility based on statistical analysis of subsequent experimental results are addressed. Percent error values in band length and conductivity are ≤8.1 and 0.37%, respectively.     

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

The replacement of hydroxyl groups by fluorine atoms on hexopyranoside scaffolds may allow access to invaluable tools for studying various biochemical processes. As part of ongoing activities toward the preparation of fluorinated carbohydrates, a systematic investigation involving the synthesis and biological evaluation of a series of mono- and polyfluorinated galactopyranosides is described. Various monofluorogalactopyranosides, a trifluorinated, and a tetrafluorinated galactopyranoside have been prepared using a Chiron approach. Given the scarcity of these compounds in the literature, in addition to their synthesis, their biological profiles were evaluated. Firstly, the fluorinated compounds were investigated as antiproliferative agents using normal human and mouse cells in comparison with cancerous cells. Most of the fluorinated compounds showed no antiproliferative activity. Secondly, these carbohydrate probes were used as potential inhibitors of galactophilic lectins. The first transverse relaxation-optimized spectroscopy (TROSY) NMR experiments were performed on these interactions, examining chemical shift perturbations of the backbone resonances of LecA, a virulence factor from Pseudomonas aeruginosa. Moreover, taking advantage of the fluorine atom, the ¹⁹F NMR resonances of the monofluorogalactopyranosides were directly monitored in the presence and absence of LecA to assess ligand binding. Lastly, these results were corroborated with the binding potencies of the monofluorinated galactopyranoside derivatives by isothermal titration calorimetry experiments. Analogues with fluorine atoms at C-3 and C-4 showed weaker affinities with LecA as compared to those with the fluorine atom at C-2 or C-6. This research has focused on the chemical synthesis of “drug-like” low-molecular-weight inhibitors that circumvent drawbacks typically associated with natural oligosaccharides.     

Synthesis and biological evaluation of some novel 1-alkyl-3-methylimidazolium carboxylate ionic liquids as potential antifungal agents

In an effort to discover lead compounds that may be of importance as potent antifungal agents, a series of novel 1-alkyl-3-methylimidazolium carboxylate ionic liquids were efficiently synthesized through a solvent-free ultrasound-assisted quaternization reaction of 1-methylimidazole and alkyl bromides RBr (R = hexyl, octyl) followed by an anion exchange process with selected carboxylate anions (cinnamate, salicylate, crotonate, and oxalate). Quantitative yields obtained were in the range of 86–94%. Structure characterization was done using FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopic techniques. All the synthesized compounds showed in vitro antifungal activity against the fungus Candida albicans with the minimum inhibitory concentrations found to be less than or equal to 1%. Preliminary cytotoxicity assays (trypan blue exclusion and MTT) were performed on all ionic liquids and findings revealed higher lymphocyte viability in 1-hexyl-3-methylimidazolium carboxylate ionic liquids than in 1-octyl-3-methylimidazolium counterparts. No extensive toxicity effect was observed with the carboxylate anion variation. Among the tested compounds, 1-hexyl-3-methylimidazolium crotonate and 1-hexyl-3-methylimidazolium oxalate exhibited the lowest cytotoxicity in the trypan blue exclusion and MTT assays, respectively. Together, our results highlight the potential of carboxylate-based ionic liquids in the development of next-generation antifungal drugs.     

Local cooperativity in an amyloidogenic state of human lysozyme observed at atomic resolution

The partial unfolding of human lysozyme underlies its conversion from the soluble state into amyloid fibrils observed in a fatal hereditary form of systemic amyloidosis. To understand the molecular origins of the disease, it is critical to characterize the structural and physicochemical properties of the amyloidogenic states of the protein. Here we provide a high-resolution view of the unfolding process at low pH for three different lysozyme variants, the wild-type protein and the mutants I56T and I59T, which show variable stabilities and propensities to aggregate in vitro. Using a range of biophysical techniques that includes differential scanning calorimetry and nuclear magnetic resonance spectroscopy, we demonstrate that thermal unfolding under amyloidogenic solution conditions involves a cooperative loss of native tertiary structure, followed by progressive unfolding of a compact, molten globule-like denatured state ensemble as the temperature is increased. The width of the temperature window over which the denatured ensemble progressively unfolds correlates with the relative amyloidogenicity and stability of these variants, and the region of lysozyme that unfolds first maps to that which forms the core of the amyloid fibrils formed under similar conditions. Together, these results present a coherent picture at atomic resolution of the initial events underlying amyloid formation by a globular protein.     

Implications of the dimuon CP asymmetry in B(d,s) decays

The D0 Collaboration reported a 3.2σ deviation from the standard model (SM) prediction in the like-sign dimuon asymmetry. Assuming that new physics contributes only to B(d,s) mixing, we show that the data can be analyzed without using the theoretical calculation of ΔΓ(s), allowing for robust interpretations. We find that this framework gives a good fit to all measurements, including the recent CDF Collaboration S(ψ?) result. The data allow universal new physics with similar contributions relative to the SM in the B(d) and B(s) systems, but favors a larger deviation in B(s) than in B(d) mixing. The general minimal flavor violation framework with flavor diagonal CP violating phases can account for the former case and remarkably even for the latter case. This observation makes it simpler to speculate about which extensions with general flavor structure may also fit the data.