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Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how physiochemical features such as size, surfactants and surface charge influence BBB passage in vivo. We now used a rat model of in vivo imaging of the retina - which is brain tissue and can reflect the situation at the BBB - to study how size and surface charge determine NPs’ ability to cross the blood-retina barrier (BRB). Interestingly, for poloxamer 188-modified, DEAE-dextran-stabilised, fluorescent PBCA NPs, decreasing the average zeta-size from 272 nm to 172 nm by centrifugation reduced the BRB passage of the NPs substantially. Varying the zeta potential within the narrow range of 0–15 mV by adding different amounts of stabiliser revealed that 0 mV and 15 mV were less desirable than 5 mV which facilitated the BRB passage. Moreover, whether the fluorescent marker was adsorbed or incorporated also influenced the transport into the retina tissue. Thus, minor changes in design of nano-carriers can alter physicochemical parameters such as size or zeta potential, thus substantially influencing NPs’ biological distribution in vivo, possibly by interactions with blood constituents and peripheral organs. [ABSTRACT FROM AUTHOR]

A fast pyrolysis process in a bubbling fluidized bed has been modeled, thoroughly reproduced and scrutinized with the help of a combined Eulerian/Lagrangian simulation method. The 3-D model is compared to experimental results from a 100 g/h bubbling fluidized bed pyrolyzer including such variables as particle composition at the outlet and gas/vapor/water yields as a function of fluidization conditions, biomass moisture concentrations, and bed temperatures. Multiprocessor simulations on a high-end computer have been carried out to enable the tracking of each of the 0.8 million individual discrete sand and biomass particles, making it possible to look at accurate and detailed multiscale information (i.e., any desired particle property, trajectory, particle interaction) over the entire particle life time. The overall thermochemical degradation process of biomass is influenced by local flow and particle properties and, therefore, accurate and detailed modeling reveals unprecedented insight into such complex processes. It has been found, that the superficial fluidization velocity is important while the particle moisture content is less significant for the final bio-oil yield. © 2011 American Institute of Chemical Engineers AIChE J, 58: 3030-3042, 2012 [ABSTRACT FROM AUTHOR]

We investigate the amplitude modulation of acoustic waves in accelerating flows, a problem that is still not fully understood, but essential to many technical applications, ranging from medical imaging to acoustic remote sensing. The proposed modeling framework is based on a convective form of the Kuznetsov equation, which incorporates the background flow field and is solved numerically by a finite-difference method. Using acoustic black and white hole analogues as model systems, we identify a modulation of the wave amplitude which is shown to be driven by the divergence/convergence of the acoustic wave characteristics in an accelerating/decelerating flow, and which is distinct from the convective amplification accompanying an acoustic emitter moving at a constant velocity. To rationalize the observed amplitude modulation, a leading-order model is derived from first principles, leveraging a similarity of the wave characteristics and the wave amplitude with respect to a modified Helmholtz number. This leading-order model may serve as a basis for the numerical prediction and analysis of the behavior of acoustic waves in accelerating flows, by taking advantage of the notion that any accelerating flow field can be described locally as a virtual acoustic black or white hole., (© 2023 Acoustical Society of America.)

Apoptosis, a key mechanism of programmed cell death, is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage. We developed a novel, non-viral gene therapy to block caspase-3 gene expression using small interfering RNA (siRNA) delivered by polybutylcyanoacrylate nanoparticles (CaspNPs). In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells, and when injected intraocularly in vivo, CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9% in rats with optic nerve crush. Longitudinal, repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1% versus 63.4% in lesioned controls. Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons, siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders. The animal study procedures were approved by the German National Act on the use of experimental animals (Ethic Committee Referat Verbraucherschutz, Veterinärangelegenheiten; Landesverwaltungsamt Sachsen-Anhalt, Halle, Germany, # IMP/G/01-1150/12 and # IMP/G/01-1469/17)., Competing Interests: None

In the wake of the COVID-19 pandemic, an increased risk of infection by virus-containing aerosols indoors is assumed. Especially in schools, the duration of stay is long and the number of people in the rooms is large, increasing the risk of infection. This problem particularly affects schools without pre-installed ventilation systems that are equipped with filters and/or operate with fresh air. Here, the aerosol concentration is reduced by natural ventilation. In this context, we are investigating the effect of large mobile air purifiers (AP) with HEPA filters on particle concentration and their suitability for classroom use in a primary school in Germany. The three tested APs differ significantly in their air outlet characteristics. Measurements of the number of particles, the particle size distribution, and the CO 2 concentration were carried out in the classroom with students (April/May 2021) and with an aerosol generator without students. In this regard, the use of APs leads to a substantial reduction of aerosol particles in the considered particle size range of 0.178-17.78 µm. At the same time, the three APs are found to have differences in their particle decay rate, noise level, and flow velocity. In addition to the measurements, the effect of various influencing parameters on the potential inhaled particle dose was investigated using a calculation model. The parameters considered include the duration of stay, particle concentration in exhaled air, respiratory flow rate, virus lifetime, ventilation interval, ventilation efficiency, AP volumetric flow, as well as room size. Based on the resulting effect diagrams, significant recommendations can be derived for reducing the risk of infection from virus-laden aerosols. Finally, the measurements were compared to computational fluid dynamics (CFD) modeling, as such tools can aid the optimal placement and configuration of APs and can be used to study the effect of the spread of aerosols from a source in the classroom.

In the minutes immediately preceding the rupture of a soap bubble, distinctive and repeatable patterns can be observed. These quasistable transient structures are associated with the instabilities of the complex Marangoni flows on the curved thin film in the presence of a surfactant solution. Here, we report a generalized Cahn-Hilliard-Swift-Hohenberg model derived using asymptotic theory that describes the quasielastic wrinkling pattern formation and the consequent coarsening dynamics in a curved surfactant-laden thin film. By testing the theory against experiments on soap bubbles, we find quantitative agreement with the analytical predictions of the nucleation and the early coarsening phases associated with the patterns. Our findings provide fundamental physical understanding that can be used to (de-)stabilize thin films in the presence of surfactants and have important implications for both natural and industrial contexts, such as the production of thin coating films, foams, emulsions, and sprays., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Superparamagnetic iron oxide nanoparticles (SPIO-NPs) have great potential to be used in different pharmaceutical applications, due to their unique and versatile physical and chemical properties. The aim of this study was to quantify in vitro cytotoxicity of dextran 70,000-coated SPIO-NPs labelled/unlabelled with rhodamine 123, in C6 glioma cells and primary hippocampal neural cells. In addition, we analyzed the in vitro and in vivo cellular uptake of labelled SPIO-NPs. The nanoparticles, with average size of 10⁻50 nm and polydispersity index of 0.37, were synthesized using Massart's co-precipitation method. The concentration-dependent cytotoxicity was quantified by using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Intracellular localization of SPIO-NPs was detected by confocal laser microscopy. In vivo confocal neuroimaging (ICON) was performed on male Wistar rats after intravitreal injection followed by ex vivo retina whole mount analysis. When used for in vitro testing concentrations in the range of diagnostic and therapeutic dosages, SPIO-NPs proved to be non-cytotoxic on C6 glioma cells for up to 24 h incubation time. The hippocampal cell culture also did not show impaired viability at low doses after 24 h incubation. Our results indicate that our dextran-coated SPIO-NPs have the potential for in vivo drug delivery applications.

This work demonstrates the use of multi-scale simulations coupled with experiments to build a quantitative prediction tool for the performance of adhesive mixtures in a dry powder inhaler (DPI). Using discrete element model (DEM), the behaviour of fine-carrier particle assemblies upon different mechanisms encountered during dose entrainment and dispersion can be described at the individual particle level. Combining these results with computational fluid dynamics (CFD) simulations, the complete dosing event from a DPI can be captured and key performance measures can be extracted. A concept of apparent surface energy, ASE, was introduced to overcome challenges associated with the complex particle properties, e.g. irregular particle shapes and surface roughness. This approach correctly predicts trends observed experimentally regarding API adhesivity, flow rate and device geometry. By incorporating the effects of drug load, critical adhesion and surface energy distributions to the simulation tool, the fine particle fraction could be predicted with good agreement to experiments for two different formulations in two different devices at two flow rates. It is concluded that multi-scale simulations provide a useful tool to support device and formulation development, as well as to gain further insight into the physical mechanisms governing dispersion from DPIs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This paper introduces a procedure for the calculation of the vertex positions in Marching-Cubes-like surface reconstruction methods, when the surface to reconstruct is characterised by a discrete indicator function. Linear or higher order methods for the vertex interpolation problem require a smooth input function. Therefore, the interpolation methodology to convert a discontinuous indicator function into a triangulated surface is non-trivial. Analytical formulations for this specific vertex interpolation problem have been derived for the 2D case by Manson et al. [Eurographics (2011) 30, 2] and the straightforward application of their method to a 3D case gives satisfactory visual results. A rigorous extension to 3D, however, requires a least-squares problem to be solved for the discrete values of a symmetric neighbourhood. It thus relies on an extra layer of information, and comes at a significantly higher cost. This paper proposes a novel vertex interpolation method which yields second-order-accurate reconstructed surfaces in the general 3D case, without altering the locality of the method. The associated errors are analysed and comparisons are made with linear vertex interpolation and the analytical formulations of Manson et al. [Eurographics (2011) 30, 2].

We derive a general integro-differential equation for the transient behavior of small-amplitude capillary waves on the planar surface of a viscous fluid in the presence of the Marangoni effect. The equation is solved for an insoluble surfactant solution in concentration below the critical micelle concentration undergoing convective-diffusive surface transport. The special case of a diffusion-driven surfactant is considered near the the critical damping wavelength. The Marangoni effect is shown to contribute to the overall damping mechanism, and a first-order term correction to the critical wavelength with respect to the surfactant concentration difference and the Schmidt number is proposed.