Dynamics of diffusion with reversible binding in microscopically heterogeneous membranes: General theory and applications to dermal penetration

Essentially all biological membranes and tissues exhibit microscopic heterogeneity in the form of cellular, lamellar or other organization, and molecular diffusion in these materials is frequently slowed by binding to elements of the microstructure (“trapping”). This paper addresses situations where binding is describable as a linear reversible process at the microscale, with forward (“on”) and reverse (“off”) rate constants k_f(x) and k_r(x) that vary with position. Very commonly it is tacitly assumed that the macroscopically observable binding behavior should follow the same rate law with the substitution of appropriate effective (tissue-average) rate constants and . This assumption is probed theoretically for spatially periodic microstructures using a judicious application of numerical calculations and asymptotic analysis to prototypical one-dimensional transport problems. We find that smooth microscopic variations produce an anomalous macroscopic exchange between free and bound solute populations that is not well described by a single pair of forward and reverse rate constants, i.e., violates the usual paradigm. In contrast, discontinuous variations (as in two-phase composite media) are evidently well described by the usual paradigm. For the latter case we derive simple and general algebraic equations giving and , and generalize them to any three-dimensional unit cell representing the tissue microstructure. Validity of the formulas is demonstrated with reference to a concrete example describing molecular diffusion through the stratum corneum (barrier) layer of skin, comprising lipid (intercellular) and corneocyte (cellular) phases. Our analysis extends coarse-graining (homogenization, effective transport) theory for irreversible trapping systems to the reversible case.     

Role of Charge and Hydrophobicity in Liprotide Formation: A Molecular Dynamics Study with Experimental Constraints

Bovine α‐lactalbumin (aLA) and oleate (OA) form a complex that has been intensively studied for its tumoricidal activity. Small‐angle X‐ray scattering (SAXS) has revealed that this complex consists of a lipid core surrounded by partially unfolded protein. We call this type of complex a liprotide. Little is known of the molecular interactions between OA and aLA, and no technique has so far provided any high‐resolution structure of a liprotide. Here we have used coarse‐grained (CG) molecular dynamics (MD) simulations, isothermal titration calorimetry (ITC) and SAXS to investigate the interactions between aLA and OA during the process of liprotide formation. With ITC we found that the strongest enthalpic interactions occurred at a molar ratio of 12.0±1.4:1 OA/aLA. Liprotides formed between OA and aLA at several OA/aLA ratios in silico were stable both in CG and in all‐atom simulations. From the simulated structures we calculated SAXS spectra that show good agreement with experimentally measured patterns of matching liprotides. The simulations showed that aLA assumes a molten globular (MG) state, exposing several hydrophobic patches involved in interactions with OA. Initial binding of aLA to OA occurs in an area of aLA in which a high amount of positive charge is located, and only later do hydrophobic interactions become important. The results reveal how unfolding of aLA to expose hydrophobic residues is important for complex formation between aLA and OA. Our findings suggest a general mechanism for liprotide formation and might explain the ability of a large number of proteins to form liprotides with OA.     

Borescopy in pressurized gas‐solid fluidized beds

A borescopic technique was used for finding the effect of pressure on the hydrodynamics of gas‐solid fluidized beds. The results showed that solids radial distribution may become more or less uniform with increasing pressure depending on the superficial gas velocity. Moreover, it is found that the solids volume fraction of the emulsion phase may decrease at relatively high pressures, only in the central region of the bed. Additionally, it is observed that with increasing pressure the bubble size generally decreased in the central regions and increased near the wall regions. This trend was more complicated at low excess gas velocities. The number of bubbles increased for the central regions and near the walls for all the performed experiments. However, this parameter showed a different trend at other radial positions. © 2018 The Authors AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers AIChE J, 64: 3303–3311, 2018     

Thin water films and particle morphology evolution in nanocrystalline MgO

A key question in the field of ceramics and catalysis is how and to what extent residual water in the reactive environment of a metal oxide particle powder affects particle coarsening and morphology. With X‐ray Diffraction (XRD) and Transmission Electron Microscopy (TEM), we investigated annealing‐induced morphology changes on powders of MgO nanocubes in different gaseous H₂O environments. The use of such a model system for particle powders enabled us to describe how adsorbed water that originates from short exposure to air determines the evolution of MgO grain size, morphology, and microstructure. While cubic nanoparticles with a predominant abundance of (100) surface planes retain their shape after annealing to T = 1173 K under continuous pumping with a base pressure of water p(H₂O) = 10^?5 mbar, higher water partial pressures promote mass transport on the surfaces and across interfaces of such particle systems. This leads to substantial growth and intergrowth of particles and simultaneously favors the formation of step edges and shallow protrusions on terraces. The mass transfer is promoted by thin films of water providing a two‐dimensional solvent for Mg²⁺ ion hydration. In addition, we obtained direct evidence for hydroxylation‐induced stabilization of (110) faces and step edges of the grain surfaces.     

High Chemical Diversity in a Wasp Pheromone: a Blend of Methyl 6-Methylsalicylate,Fatty Alcohol Acetates and Cuticular Hydrocarbons Releases Courtship Behavior in the Drosophila Parasitoid Asobara tabida

Wasps of genus Asobara, a larval parasitoid of Drosophila, have become model organisms for the study of host-parasite interactions. However, little is known about the role of pheromones in locating mates and courtship behavior in this genus. In the present study, we aimed to identify the female courtship pheromone in Asobara tabida. The chemical compositions of solvent extracts from male and female wasps were analyzed by GC/MS. These extracts, fractions thereof, and synthetic pheromone candidates were tested for their activity in behavioral bioassays. The results demonstrate that the courtship pheromone of A. tabida is characterized by a remarkable chemical diversity. A multi-component blend of female-specific compounds including methyl 6-methylsalicylate (M6M), fatty alcohol acetates (FAAs), and cuticular hydrocarbons (CHCs) released male courtship behavior. Using a combinatory approach that included both purified natural products and synthetic analogs, it was shown that none of the three chemical classes alone was sufficient to release a full behavioral response in males. However, a blend of M6M and FAAs or combinations of one or both of these with female-derived CHCs resulted in wing-fanning responses by males comparable to those elicited by the crude extract of females. Thus, components from all three chemical classes contribute to the bioactivity of the pheromone, but none of the elements plays a key role or is irreplaceable. The fact that one of the FAAs, vaccenyl acetate, is also used as a kairomone by Asobara females to locate Drosophila hosts suggests that a pre-existing sensory responsiveness to vaccenyl acetate might have been involved in the evolution of the female sex pheromone in Asobara.     

Photocaged Hoechst Enables Subnuclear Visualization and Cell Selective Staining of DNA in vivo

Selective targeting of DNA by means of fluorescent labeling has become a mainstay in the life sciences. While genetic engineering serves as a powerful technique and allows the visualization of nucleic acid by using DNA-targeting fluorescent fusion proteins in a cell-type- and subcellular-specific manner, it relies on the introduction of foreign genes. On the other hand, DNA-binding small fluorescent molecules can be used without genetic engineering, but they are not spatially restricted. Herein, we report a photocaged version of the DNA dye Hoechst33342 (pcHoechst), which can be uncaged by using UV to blue light for the selective staining of chromosomal DNA in subnuclear regions of live cells. Expanding its application to a vertebrate model organism, we demonstrate uncaging in epithelial cells and short-term cell tracking in vivo in zebrafish. We envision pcHoechst as a valuable tool for targeting and interrogating DNA with precise spatiotemporal resolution in living cells and wild-type organisms.     

Solid‐state NMR study of spin finish of thermally treated PAN and PAN/CNT precursor fibers

Dry‐jet wet‐spun polyacrylonitrile (PAN) and PAN/carbon nanotubes (CNTs) precursor fibers coated by spin finishes were characterized using the solid‐state ¹H nuclear magnetic resonance technique. Series of fiber samples were prepared upon thermal treatment at different temperatures (room temperature to 180°C). Using the Hahn echo sequence, relatively mobile components were identified and the effect of the heat treatment on those components was studied. It was observed that the mobile components are mainly the spin finishes. Heat treatment caused loss of one of the spin finishes (Type B) to a great extent (～80%), whereas the other two spin finishes (Type A and Type C) were more stable. Additional information regarding the change in molecular mobility due to heat treatment was obtained by the spin‐lattice relaxation time ( T₁ ) analysis. It was found that the presence of CNT affects the T₁ relaxation time of the polymer in the composite fiber, however, that of relatively mobile components remains unaffected. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40734.     

MA‐NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules

In the past few years, gallium‐68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA‐NOTMP), a new C‐functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for ⁶⁸Ga (low ligand concentration, labelling at low pH even at room temperature). A “ready‐to‐be‐grafted” bifunctional chelating agent (p‐NCS‐Bz‐MA‐NOTMP) was prepared to allow ⁶⁸Ga labelling of sensitive biological vectors. Conjugation to a bombesin_(7–14) derivative was performed, and preliminary in vitro experiments demonstrated the potential of MA‐NOTMP in the development of radiopharmaceuticals. This new chelator is therefore of major interest for labelling sensitive biomolecules, and further in vivo experiments will soon be performed.     

Enhancing the temperature stability of PLA by compounding strategies

The low thermal stability of polylactid acid (PLA) limits its use for various applications such as microwave‐ready dishes or hot beverage packaging. Furthermore, contained items might be damaged by occurring temperature peaks during transport (e.g., shipping container internal temperature exceeds 80°C) or other usage (e.g., car dashboard heated by sun). The aim of this study was the development of a PLA compound with an operating temperature above 100°C. Therefore, different formulations (e.g., stereocomplex of PLLA and PDLA, cross‐linking of PLA or use of commercial additives) were identified and compounds with varying conditions produced and tested regarding their thermal and mechanical properties. The results showed clearly possible routes for improving the thermal properties of PLA. Using such compounds respectively processing routes and additives helps to overcome one of the most significant problems when using PLA. The higher operating temperature of this biopolymer will lead to a wider field of application and will avoid shipping hazards. POLYM. ENG. SCI., 55:2849–2858, 2015. © 2015 Society of Plastics Engineers