Segregation by thermal diffusion of an intruder in a moderately dense granular fluid

A solution of the inelastic Enskog equation that goes beyond the weak dissipation limit and applies for moderate densities is used to determine the thermal diffusion factor of an intruder immersed in a dense granular gas under gravity. This factor provides a segregation criterion that shows the transition between the Brazil-nut effect (BNE) and the reverse Brazil-nut effect (RBNE) by varying the parameters of the system (masses, sizes, density and coefficients of restitution). The form of the phase-diagrams for the BNE/RBNE transition depends sensitively on the value of gravity relative to the thermal gradient, so that it is possible to switch between both states for given values of the parameters of the system. Two specific limits are considered with detail: (i) absence of gravity, and (ii) homogeneous temperature. In the latter case, after some approximations, our results are consistent with previous theoretical results derived from the Enskog equation. Our results also indicate that the influence of dissipation on thermal diffusion is more important in the absence of gravity than in the opposite limit. The present analysis extends previous theoretical results derived in the dilute limit case [V. Garz\'o, Europhys. Lett. {\bf 75}, 521 (2006)] and is consistent with the findings of some recent experimental results.Comment: 10 figure

Competition between nucleation and confinement in the crystallization of poly(ethylene glycol)/ large aspect ratio hectorite nanocomposites

Unformatted preprint version of the submitted articleThe overall crystallization kinetics of polymer nanocomposites is determined by nucleation and crystal growth, which are both greatly affected by confinement. Heterogeneous nucleation is influenced by the interphase area between filler and polymer matrix. Starting with a homogeneous nematic aqueous dispersion of a mixture containing polyethylene glycol (PEG) and varying amounts of a high aspect ratio layered silicate (hectorite, Hec), nanocomposite films were casted displaying a systematic variation of the degree of PEG confinement. This is achieved by a partial phase segregation upon drying, where independently of filler content a thermodynamically stable, 1 dimensional crystalline hybrid with constant volume of intercalated PEG (0.81 nm corresponding to a fraction 75 wt% and 55 vol%, respectively) is formed. This intercalated hybrid phase is incorporated into segregated PEG domains. The segregation is a kinetically controlled process and the length scale of segregation increases with PEG available in surplus of the hybrid. Due to the very large lateral extension of the Hec, the segregated domains are increasingly two dimensional. As evidenced by transmission electron micrographs and powder X-ray diffraction, the segregation produces composite structures where, in dependency of filler content, PEG slabs of different thickness are separated by domains of the intercalated hybrid material. The crystallization behavior of these bi-phasic materials was investigated by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (PLOM). DSC results reveal a competition between the nucleating effect of Hec, which was particularly important at low amounts, and the PEG confinement effect at higher filler loadings. Applying a self-nucleation protocol, the nucleation efficiency of the hectorite was shown to be up to 67%. The isothermal crystallization kinetics accelerated at low Hec contents (nucleation), went through a maximum and then decreased (confinement) as Hec content increased. Additionaly, a clear correlation between filler content and the Avrami index was obtained supporting the increase in confinement as filler loading increased.The authors thank Florian Puchtler for producing the synthetic sodium hectorite, Marco Schwarzmann for the SEM and TEM measurements and sample preparation via cryo ion slicing, and Dr. Sabine Rosenfeldt for the SAXS measurements. We appreciate the support of the Keylab for Optical and Electron Microscopy and the Keylab for Small Scale Polymer Processing of the Bavarian Polymer Institute (BPI). This work was supported by the German Science Foundation (DFG) within the collaborative research project SFB 1357. J.M. acknowledges support from the Provincial Council of Gipuzkoa under the program Fellow Gipuzkoa and partial financial support to the IBERDROLA Foundation. J.L.O.M. wish to thank the National Council of Science and Technology (CONACYT) in México for his grant 471837. We acknowledge funding by Mineco MAT2017-83014-C2-1-P project and by the Basque Government through grant IT1309-19. This work has also received funding from the European Union´s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 778092

Renin inhibition by substituted piperidines: A novel paradigm for the inhibition of monomeric aspartic proteinases?

BackgroundThe aspartic proteinase renin catalyses the first and rate-limiting step in the conversion of angiotensinogen to the hormone angiotensin II, and therefore plays an important physiological role in the regulation of blood pressure. Numerous potent peptidomimetic inhibitors of this important drug target have been developed, but none of these compounds have progressed past clinical phase II trials. Limited oral bioavailability or excessive production costs have prevented these inhibitors from becoming new antihypertensive drugs. We were interested in developing new nonpeptidomimetic renin inhibitors.ResultsHigh-throughput screening of the Roche compound library identified a simple 3,4-disubstituted piperidine lead compound. We determined the crystal structures of recombinant human renin complexed with two representatives of this new class. Binding of these substituted piperidine derivatives is accompanied by major induced-fit adaptations around the enzyme's active site.ConclusionsThe efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases