Phospholipid‐Free Small Unilamellar Vesicles for Drug Targeting to Cells in the Liver

It is reported that cholesterol (Chol) and TWEEN 80 at a molar ratio of 5:1 can form small unilamellar vesicles (SUVs) using a staggered herringbone micromixer. These phospholipid‐free SUVs (PFSUVs) can be actively loaded with a model drug for targeting hepatocytes via the endogenous apolipoprotein mechanism. PFSUVs particles with compositions of Chol:TWEEN 80 ranging between 1.5:1 and 5:1 (mol/mol) can be produced with a mean diameter of ≈80 nm, but only the high‐Chol formulations (3:1 and 5:1) can retain a transmembrane gradient of ammonium sulfate for active loading of doxorubicin (DOX). Under cryo‐transmission electron microscopy, PFSUVs‐DOX displays a unilamellar bilayer structure with DOX molecules forming spindle‐shape aggregates inside the aqueous core. Relative to PEGylated liposomal doxorubicin (PLD) that exhibits little interaction with cells in various conditions, the cellular uptake of PFSUVs‐DOX is dependent on the presence of serum and enhanced with an increased concentration of apolipoproteins. After intravenous injection, the vast majority of PFSUVs‐DOX accumulates in the liver and DOX is detected in all liver cells (predominantly the hepatocytes), while PLD is captured only by the sinusoidal cells (i.e., macrophages). This report discloses an innovative lipid bilayer vesicle for highly efficient and selective hepatocyte targeting.     

Uncertainty-Wise Cyber-Physical System test modeling

Software and Systems Modeling - It is important that a Cyber-Physical System (CPS) with uncertainty in its behavior caused by its unpredictable operating environment, to ensure its reliable...     

Risk assessment of dietary exposure to perchlorate for the Austrian population

Perchlorate is frequently found as contaminant in a variety of food. Based on analytical data of perchlorate occurrence in food products from the Austrian market, this study calculated dietary perchlorate exposure of the Austrian population for the three age classes of adults, children and infants. Furthermore, a detailed risk assessment was conducted based on the tolerable daily intake (TDI) of 0.3 µg/kg body weight/day, established by the European Food Safety Authority in 2014. Calculations of a scenario of average food consumption did not indicate elevated health risks by dietary perchlorate uptake. Exposure estimates reached only 12%, 26% and 24% of the TDI for adults, children and infants, respectively. However, in a scenario of high consumption, the TDI was exceeded by all age classes with 132%, 161% and 156%. The major cause for this exceedance is the comparatively high perchlorate contamination of spinach, but also other leaf vegetables, legumes and pineapples, leading to elevated exposure of high consumers. Our calculations reveal that the current provisional intra-Union trade reference level for perchlorate in spinach of 0.2 mg/kg, advocated by the European Commission, is not sufficient to protect high consumers against possible health risks. In order to reduce health risks to a tolerable level for all consumers, lowering of the regulatory maximum perchlorate concentrations is indicated. Moreover, a generally diversified diet can also counteract excessive exposure to perchlorate as well as to other harmful food contaminants.     

On the benefits of a stress criterion for the simulation of cup drawing process

Experimental and numerical cup drawing process has been investigated on 0.65 mm zinc sheets. The cup exhibits anisotropic earrings due to the material microstructure. The material formability is studied through elliptical bulge tests in the rolling, diagonal and transverse direction. High anisotropy of the formability is observed. The numerical simulation of cup drawing is then made and demonstrates the correct fitting with experimental results. A stress formability criterion developed by Jansen et al. [14] is then implemented into a finite element method software and applied to predict the material rupture observed for some process conditions. The risk zone of the cup is subjected to some strain path changes according to the simulation whereas the strain value does not explain the rupture according to the experimental formability measured by the bulge tests. It has been shown that the rupture is due to some critical stresses, which are reached in the risk zone of the cup. The use of the stress criterion and its non-dependence on the strain path change allows the fracture prediction. Finally, the numerical fracture propagation by the “kill element method”, as briefly discussed by Bouchard et al. [4], is used and shows a good similarity with the experience.     

Manipulating feature sizes in Si-based grating structures by thermal oxidation

We report a method for manipulating feature sizes in Si-based grating structures by thermal oxidation, which allows the realization of fin width/period ratios not directly accessible by laser interference lithography. Taking advantage of the expansion in volume associated with the thermal oxidation of Si, grating structures with very high fin width/period ratios of the order of 0.96 were obtained, whereas subsequent chemical etching of the oxide yields grating structures with fin width/period ratios as small as ～0.06.     

Micropellets coated with Kollicoat® Smartseal 30D for taste masking in liquid oral dosage forms

The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat^® Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat^® Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3?weeks, which exceeds the usual period of application.     

From elastic homogenization to upscaling of non-Newtonian fluid flows in porous media

Upscaling behaviors of heterogeneous microstructures to define macroscopic effective media is of major interest in many areas of computational mechanics, in particular those related to materials and processes engineering. In this paper, we explore the possibility of defining a macroscopic behavior manifold from microscopic calculations, and then use it directly for efficiently performing manifold-based simulations at the macroscopic scale. We consider in this work upscaling of non-Newtonian flows in porous media, and more particularly the ones involving short-fibre suspensions.     

Anwendung des Neutralisationspotenzials bei der Bilanzierung von Säure-Base-Reaktionen im Umfeld des Braunkohlebergbaues

Acidic conditions of seepage and groundwater originating from open pit minings in Lusatia are described using the neutralization potential, which is based on the concept of acidity. Acid formation and buffer reactions can be reduced to three elemental reactions: oxidation of pyrit/reduction of sulfate, dissolution of carbonate and gypsum equilibrium. These reactions are combined in a genetic model in order to interpret the origin of mineral and acid contents of different groundwaters influenced by lignite mining. The statistical results of these calculations are summarised in order to calibrate parameters of a prognostic model. The method described here is used to prepare restoration measures.