Physiology and Pathophysiology of Human Airway Mucus

The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na+ absorptive vs Cl- secretory rates to maintain mucus hydration in health. In disease, mucus becomes hyperconcentrated (dehydrated). Multiple mechanisms derange the ion transport pathways that normally hydrate mucus in muco-obstructive lung diseases, e.g., CF, COPD, NCFB, and PCD. A key step in muco-obstructive disease pathogenesis is the osmotic compression of the mucus layer onto the airway surface with the formation of adherent mucus plaques and plugs, particularly in distal airways. Mucus plaques create locally hypoxic conditions and produce airflow obstruction, inflammation, infection, and, ultimately, airway wall damage. Therapies to clear adherent mucus with hydrating and mucolytic agents are rational, and strategies to develop these agents are reviewed.

Core-edge 2D fluid modeling of full tokamak discharge with varying magnetic equilibrium: from WEST start-up to ramp-down

In the present work we investigate for the first time the 2D fluid transport of the plasma in WEST during an entire discharge from the start-up to the ramp-down (shot #54487). The evolution of density profile, electron and ion temperatures together with the experimental magnetic equilibrium, total current and gas-puff rate is investigated. Comparisons with the interferometry diagnostic show a remarkable overall qualitative agreement during the discharge that can be quantitative at some locations in the plasma core. If at the onset of the X-points during the ramp-up the electron heat flux is dominant at the target, present results show that the ion heat flux becomes dominant during the stationary phase of the discharge. Using a simple model for erosion, present results assess the tungsten sputtering due to deuterium ions during the start-up and ramp-up phases of the discharge and confirms the need to consider full discharge simulation to accurately treat the W source of contamination. This work also demonstrates the interest of developing magnetic equilibrium free solver including efficient time integration to step toward predictive capabilities in the future for fusion operation.

Energetic Formulation of Large-Deformation Poroelasticity

The modeling of coupled fluid transport and deformation in a porous medium is essential to predict the various geomechanical process such as CO2 sequestration, hydraulic fracturing, and so on. Current applications of interest, for instance, that include fracturing or damage of the solid phase, require a nonlinear description of the large deformations that can occur. This paper presents a variational energy-based continuum mechanics framework to model large-deformation poroelasticity. The approach begins from the total free energy density that is additively composed of the free energy of the components. A variational procedure then provides the balance of momentum, fluid transport balance, and pressure relations. A numerical approach based on finite elements is applied to analyze the behavior of saturated and unsaturated porous media using a nonlinear constitutive model for the solid skeleton. Examples studied include the Terzaghi and Mandel problems; a gas-liquid phase-changing fluid; multiple immiscible gases; and unsaturated systems where we model injection of fluid into soil. The proposed variational approach can potentially have advantages for numerical methods as well as for combining with data-driven models in a Bayesian framework.

Confirmation and variability of the Allee effect in Dictyostelium discoideum cell populations,possible role of chemical signaling within cell clusters

In studies of the unicellular eukaryote Dictyostelium discoideum, many have anecdotally observed that cell dilution below a certain "threshold density” causes cells to undergo a period of slow growth (lag). However, little is documented about the slow growth phase and the reason for different growth dynamics below and above this threshold density. In this paper, we extend and correct our earlier work to report an extensive set of experiments, including the use of new cell counting technology, that set this slow-to-fast growth transition on a much firmer biological basis. We show that dilution below a certain density (around 10E4 cells/ml) causes cells to grow slower on average and exhibit a large degree of variability: sometimes a sample does not lag at all, while sometimes it takes many moderate density cell cycle times to recover back to fast growth. We perform conditioned media experiments to demonstrate that a chemical signal mediates this endogenous phenomenon. Finally, we argue that while simple models involving fluid transport of signal molecules or cluster-based signaling explain typical behavior, they do not capture the high degree of variability between samples but nevertheless favor an intra-cluster mechanism.

Open capillary siphons

Flow in the inverted U-shaped tube of a conventional siphon can be established and maintained only if the tube is filled and closed, so that air does not enter. We report on siphons that operate entirely open to the atmosphere by exploiting surface tension effects. Such capillary siphoning is demonstrated by paper tissue that bridges two containers and conveys water from the upper to the lower. We introduce a more controlled system consisting of grooves in a wetting solid, formed here by pressing together hook-shaped metallic rods. The dependence of flux on siphon geometry is systematically measured, revealing behaviour different from the conventional siphon. The flux saturates when the height difference between the two container's free surfaces is large; it also has a strong dependence on the climbing height from the source container's free surface to the apex. A one-dimensional theoretical model is developed, taking into account the capillary pressure due to surface tension, pressure loss due to viscous friction, and driving by gravity. Numerical solutions are in good agreement with experiments, and the model suggests hydraulic interpretations for the observed flux dependence on geometrical parameters. The operating principle and characteristics of capillary siphoning revealed here can inform biological phenomena and engineering applications related to directional fluid transport.

Entropy Analysis for Cilia-Generated Motion of Cu-Blood Flow of Nanofluid in an Annulus

In this study, a novel model of entropy generation effects measured in the Cu-blood flow of a nanofluid under the effect of ciliary-oriented motion is proposed. The effects of viscous dissipation are also taken into account. The physical model was composed with the incorporation of a low Reynolds number and long-wavelength phenomena. The exact solutions for the axial velocity, temperature and pressure gradient distribution were achieved successfully. Key findings are presented through a strategy of plotting the significant factors affecting the physical quantities of the stream. It was found that the heat absorption parameter and Brownian motion accounted for the large thermal transfer rate, while the effect of entropy was minimal compared to these factors in the center of the flow but increased on the walls in the case of Cu-blood flow. It can also be added that a more intense flow gave rise to the entropy effects. This study may be helpful in medical science as cilia play vital roles, which include cell migration and external fluid transport, in human tissues and some key organs. Moreover, the considered annulus-shaped geometry gives vital readings that are used in medical equipment such as endoscopes.