Engineering rotating apical-out airway organoid for assessing respiratory cilia motility

Motile cilia project from the airway apical surface and directly interface with inhaled external environment. Owing to cilia\u27s nanoscale dimension and high beating frequency, quantitative assessment of their motility remains a sophisticated task. Here we described a robust approach for reproducible engineering of apical-out airway organoid (AOAO) from a defined number of cells. Propelled by exterior-facing cilia beating, the mature AOAO exhibited stable rotational motion when surrounded by Matrigel. We developed a computational framework leveraging computer vision algorithms to quantify AOAO rotation and correlated it with the direct measurement of cilia motility. We further established the feasibility of using AOAO rotation to recapitulate and measure defective cilia motility caused by chemotherapy-induced toxicity and by CCDC39 mutations in cells from patients with primary ciliary dyskinesia. We expect our rotating AOAO model and the associated computational pipeline to offer a generalizable framework to expedite the modeling of and therapeutic development for genetic and environmental ciliopathies

Single molecule detection with graphene and other two-dimensional materials: nanopores and beyond

Supramolecular & Biomaterials Chemistr

Computational fluid dynamics simulation of fluid particle fragmentation in turbulent flows

A simulation methodology is presented that allows detailed studies of the breakup mechanism of fluid particles in turbulent flows. The simulations, based on large eddy and volume of fluid simulations, agree very well with high-speed measurements of the breakup dynamics with respect to deformation time and length scales, and also the resulting size of the daughter fragments. The simulations reveal the size of the turbulent vortices that contribute to the breakup and how fast the interaction and energy transfer occurs. It is concluded that the axis of the deformed particle and the vortex core axis are aligned perpendicular to each other, and that breakup sometimes occurs due to interaction with two vortices at the same time. Analysis of the energy transfer from the continuous phase turbulence to the fluid particles reveals that the deformed particle attains it maximum in interfacial energy before the breakup is finalized. Similar to transition state theory in chemistry this implies that an activation barrier exists. Consequently, by considering the dynamics of the phenomenon, more energy than required at the final stage needs to be transferred from the turbulent vortices for breakup to occur. This knowledge helps developing new, more physical sound models for the breakup phenomenon required to solve scale separation problems in computational fluid dynamics simulations

Computational and experimental investigation of the breakup mechanism of bubbles and drops in turbulent flows

This work focuses on understanding the breakup mechanism of bubbles and drops in turbulent multiphase flow. For this purpose CFD simulations based on a combination of large eddy simulations (LES) and volume of fluid (VOF) are validated using high speed camera measurement of the breakup dynamics. Very good agreement was found, both for deformation time and length scales and for the resulting size of the daughter fragments. The analysis reveals that eddies larger than the fluid particles also contribute to the breakup. It was also observed that the axis of the deformed particle and the vortex core axis were aligned perpendicular to each other, and that the breakup can sometimes occur due to interaction with two eddies at the same time. In these cases the vortex core axes were also aligned perpendicular. This means that more energy will be available and that the breakup rate will be affected

Effects of Different Doses of Metformin on Serum Fatty Acid Composition in Type 2 Diabetic Rats

Background: Several studies have shown association of fatty acids with type 2 diabetes (T2D), as well as metformin effects on blood glucose concentrations through affecting lipid metabolism. Objectives: Since the exact therapeutic mechanism of metformin is not clear, in this study we investigated effects of different doses of metformin on serum fatty acids in rats with T2D. Materials and Methods: Twenty-five adult albino male Wistar rats were divided into the following groups: Healthy, untreated T2D, and T2D rats receiving metformin for 4 weeks with doses of 100, 150, and 200 mg/kg/d. Serum insulin and triglyceride (TG) were measured using commercial kits. Serum total lipids were extracted by the Bligh-Dyer method and then compositions of fatty acids were evaluated using gas chromatograph. Results: Monounsaturated fatty acid (MUFA) levels in T2D rats were lower than those in healthy rats (P < 0.05). We also observed that diabetic rats treated with 100 or 150 mg/kg/d of metformin had higher levels of arachidonic acid and polyunsaturated fatty acids (PUFA) in comparison with the healthy group (P < 0.05). Moreover, the T2D+Met (150 mg/kg) group showed increased levels of MUFA compared with the T2D group. Such a difference was seen in levels of arachidonic acid between the T2D+Met 100 mg/ kg group and untreated T2D group. In the group treated with high doses of metformin (200 mg/kg/d), levels of palmitic acid, palmitoleic acid, and saturated fatty acid (SFA) were higher and levels of oleic acid, linoleic acid, arachidonic acid, MUFA, PUFA, and also SFA/UFA ratio were lower compared with other metformin treated and untreated groups (P < .05). In untreated T2D group, there were positive correlations between glucose levels and linoleic acid and PUFA levels (r = 0.707, P = .049 and r = 0.726, P = .041 respectively). Arachidonic acid levels were positively correlated with glucose levels in T2D rats treated with 100 mg/kg/d of metformin (r = 0.969, P = .031). Conclusions: Our study showed that different doses of metformin could have different effects on serum levels of saturated and unsaturated fatty acids, as 200 mg/kg/d of metformin could increase and decrease saturated and unsaturated fatty acids respectively, while lower doses increased unsaturated fatty acids, particularly arachidonic acid

Resource scarcity in palladium membrane applications for carbon capture in integrated gasification combined cycle units

Recently, many reviews on pre-combustion CO2 capture (CCS) in an IGCC plant have been focused on the techno-economic performance of palladium-based membrane reactor modules downstream of conventional steam reforming or shift reactors. Although the determination and minimisation of the amount of palladium necessary for a specific power production capacity has been the target of many research studies, surprisingly little attention has been paid in the open literature to the availability of this metal in the large quantities required for large scale applications. To fill this gap, the scope of this work was to compare the amount of palladium needed for pre-combustion CCS with Pd-membranes and the available production capacity of palladium. Two specific techno-economic studies with a different net IGCC power output were selected from the literature. In each case, the amount of palladium that is necessary for the plant to be in operation was compared with the world supply and demand for palladium. The results show that even for a power plant of "only" 1 GWe net electricity production utilizing membranes with the best reported performance, a relatively large (~0.7%) amount of palladium is required compared to the total world supply. Considering the total worldwide electricity production from fossil fuels (14,455 TWh in 2010) a tremendous increase in the world supply of Palladium would be required to redirect from the traditional IGCC power plants without CO2 capture units to the new membrane technology. We conclude that large scale pre-combustion capture of CO2 using palladium membranes seems to be unfeasible and research on Pd-based membrane reactors should focus on small(er) scale applications