Microenvironment-mediated cancer dormancy: Insights from metastability theory

Dormancy is an evolutionarily conserved protective mechanism widely observed in nature. A pathological example is found during cancer metastasis, where cancer cells disseminate from the primary tumor, home to secondary organs, and enter a growth-arrested state, which could last for decades. Recent studies have pointed toward the microenvironment being heavily involved in inducing, preserving, or ceasing this dormant state, with a strong focus on identifying specific molecular mechanisms and signaling pathways. Increasing evidence now suggests the existence of an interplay between intracellular as well as extracellular biochemical and mechanical cues in guiding such processes. Despite the inherent complexities associated with dormancy, proliferation, and growth of cancer cells and tumor tissues, viewing these phenomena from a physical perspective allows for a more global description, independent from many details of the systems. Building on the analogies between tissues and fluids and thermodynamic phase separation concepts, we classify a number of proposed mechanisms in terms of a thermodynamic metastability of the tumor with respect to growth. This can be governed by interaction with the microenvironment in the form of adherence (wetting) to a substrate or by mechanical confinement of the surrounding extracellular matrix. By drawing parallels with clinical and experimental data, we advance the notion that the local energy minima, or metastable states, emerging in the tissue droplet growth kinetics can be associated with a dormant state. Despite its simplicity, the provided framework captures several aspects associated with cancer dormancy and tumor growth.

Investigation of the effect of air humidity on the condensation growth of levitating liquid microdroplets

Two-dimensional structured arrays of liquid microdroplets levitated over a hot liquid surface have been investigated in several recent papers, but the nature of this phenomenon has not yet been fully understood. In this work we investigate the effect of air humidity on the condensation growth of levitating liquid microdroplets. It was found that the higher the relative humidity of the surrounding air, the lower the rate of the droplet growth.

Simulation-aided characterization of a versatile water-based condensation particle counter for atmospheric airborne research

Capturing the vertical profiles and horizontal variations of atmospheric aerosols often requires accurate airborne measurements. With the advantage of avoiding health and safety concerns related to the use of butanol or other chemicals, water-based condensation particle counters have emerged to provide measurements under various environments. However, airborne deployments are relatively rare due to the lack of instrument characterization under reduced pressure at flight altitudes. This study investigates the performance of a commercial “versatile” water-based condensation particle counter (vWCPC, model 3789, TSI, Shoreview, MN, USA) under various ambient pressure conditions (500–920 hPa) with a wide range of particle total number concentrations (1500–70 000 cm−3). The effect of conditioner temperature on vWCPC 3789 performance at low pressure is examined through numerical simulation and laboratory experiments. We show that the default instrument temperature setting of 30 ∘C for the conditioner is not suitable for airborne measurement and that the optimal conditioner temperature for low-pressure operation is 27∘. Under the optimal conditioner temperature (27∘), the 7 nm cut-off size is also maintained. Additionally, we show that insufficient droplet growth becomes more significant under the low-pressure operation. The counting efficiency of the vWCPC 3789 can vary up to 20 % for particles of different chemical compositions (e.g., ammonium sulfate and sucrose particles). However, such variation is independent of pressure.

Computational analysis of homogeneous nucleation and droplet growth applied to natural gas separators

A natural gas droplet is generated at certain thermodynamic conditions through three stages: supersaturation, where the gas has more molecules than it should have in equilibrium, forming “embryos” of liquid phase; nucleation, where embryos form groups of different shapes and sizes of nanometer order; and the droplet growth, where the number of molecules increases until equilibrium is reached. In this paper, the homogeneous nucleation and droplet growth of natural gas applied to gravitational separators operating at high pressure conditions (7MPa) are analyzed. The results showed that at a high pressure, the initial drop size reached was 8.024 nanometers and the final diameter of the drop was 4.18 micrometers.

A predictive thermodynamic framework of cloud droplet activation for chemically unresolved aerosol mixtures, including surface tension, non-ideality, and bulk–surface partitioning

This work presents a thermodynamically consistent framework that enables self-contained, predictive Köhler calculations of droplet growth and activation with considerations of surface adsorption, surface tension reduction, and non-ideal water activity for chemically complex and unresolved surface-active aerosol mixtures. The common presence of surface-active species in atmospheric aerosols is now well-established. However, the impacts of different effects driven by surface activity, in particular bulk–surface partitioning and resulting bulk depletion and/or surface tension reduction, on aerosol hygroscopic growth and cloud droplet activation remain to be generally established. Because specific characterization of key properties, including water activity and surface tension, remains exceedingly challenging for finite-sized activating droplets, a self-contained and thermodynamically consistent model framework is needed to resolve the individual effects of surface activity during droplet growth and activation. Previous frameworks have achieved this for simple aerosol mixtures, comprising at most a few well-defined chemical species. However, atmospheric aerosol mixtures and more realistic laboratory systems are typically chemically more complex and not well-defined (unresolved). Therefore, frameworks which require specific knowledge of the concentrations of all chemical species in the mixture and their composition-dependent interactions cannot be applied. For mixtures which are unresolved or where specific interactions between components are unknown, analytical models based on retrofitting can be applied, or the mixture can be represented by a proxy compound or mixture with well-known properties. However, the surface activity effects evaluated by such models cannot be independently verified. The presented model couples Köhler theory with the Gibbs adsorption and Szyszkowski-type surface tension equations. Contrary to previous thermodynamic frameworks, it is formulated on a mass basis to obtain a quantitative description of composition-dependent properties for chemically unresolved mixtures. Application of the model is illustrated by calculating cloud condensation nuclei (CCN) activity of aerosol particles comprising Nordic aquatic fulvic acid (NAFA), a chemically unresolved and strongly surface-active model atmospheric humic-like substance (HULIS), and NaCl, with dry diameters of 30–230 nm and compositions spanning the full range of relative NAFA and NaCl mixing ratios. For comparison with the model presented, several other predictive Köhler frameworks, with simplified treatments of surface-active NAFA, are also applied. Effects of NAFA surface activity are gauged via a suite of properties evaluated for growing and activating droplets. The presented framework predicts a similar influence of surface activity of the chemically complex NAFA on CCN activation as was previously shown for single, strong surfactants. Comparison to experimental CCN data shows that NAFA bulk–surface partitioning is well-represented by Gibbs adsorption thermodynamics. Contrary to several recent studies, no evidence of significantly reduced droplet surface tension at the point of activation was found. Calculations with the presented thermodynamic model show that throughout droplet growth and activation, the finite amounts of NAFA in microscopic and submicron droplets are strongly depleted from the bulk, due to bulk–surface partitioning, because surface areas for a given bulk volume are very large. As a result, both the effective hygroscopicity and ability of NAFA to reduce droplet surface tension are significantly lower in finite-sized activating droplets than in macroscopic aqueous solutions of the same overall composition. The presented framework enables the influence of surface activity on CCN activation for other chemically complex and unresolved aerosol mixtures, including actual atmospheric samples, to be systematically explored. Thermodynamic input parameters can be independently constrained from measurements, instead of being either approximated by a proxy or determined by retrofitting, potentially confounding several mechanisms influenced by surface activity.

Investigation on collision-coalescence of droplets under the synergistic effect of charge and sound waves: orthogonal design optimization

As an efficient approach to improve the visibility, defogging technology is essential for the operation of ports and airports. This paper proposes a new and hybrid defogging technology, i.e. electric–acoustic defogging method. Specifically, the droplets are charged by corona discharge, which is beneficial to overcome the hydrodynamic interaction force to improve the droplet collision efficiency. Meanwhile, sound waves (especially acoustic turbulence) promote the relative movement of droplets to increase the collision probability. In this study, the effects of acoustic frequency ( f ), sound pressure level (SPL), and voltage (V) on the droplet growth ratio were studied by orthogonal design analysis. The results of difference analysis and multi-factor variance analysis show that frequency and sound pressure level are the dominant factors that affect the collision of droplets, and the effect of voltage is relatively weak. And f = 400 Hz, SPL = 132 dB, and V = -7.2 kV are the optimal parameters in our experiment. In addition, we further studied the impact of single factor on droplet growth ratio. The results show that there is an optimal frequency of 400 Hz. That is, the impact of frequency is non-linear. The droplet growth ratio increases with sound pressure level and voltage level. The new technology proposed in this paper can provide a new approach for defogging in open space.

mmBCFA C17iso ensures endoplasmic reticulum integrity for lipid droplet growth

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.

Dropwise Condensation Mechanism on Smooth Hydrophilic Surfaces

The objective of this work is to identify the mechanism of dropwise condensation on a smooth solid surface. We investigate the stable dropwise condensation that occurs at a droplet growth rate of 1 µm/s in diameter on a gold-coated glass surface. Additionally, we present our observations on unstable dropwise condensation, i.e., degradation of dropwise condensation of steam on a gold surface. Surface Plasmon Resonance Imaging (SPRi) is used to evaluate the existence and structure of thin films and occurrence of initial nuclei during condensation. SPRi approach used in this study has lateral resolutions of 4–10 µm, thickness resolutions of 0.1–1 nm, and temporal resolutions of 200–10,000 frames per second (FPS). Visualization of the onset of stable dropwise condensation suggests droplets form at heterogeneous nucleation sites and that no film greater than a monolayer exists on the surface before the formation of droplets. Observation of the unstable dropwise condensation of steam shows the existence of water films that are several nanometers thick between droplets. This work shows that neither the nucleation theory nor film rupture theory can individually explain the physics of dropwise condensation. Therefore, there is a need for a more comprehensive theory that can explain the mechanism of dropwise condensation.

Simulation-aided characterization of a versatile water condensation particle counter for atmospheric airborne research

Capturing the vertical profiles and horizontal variations of atmospheric aerosols often requires accurate airborne measurements. With the advantage of avoiding health and safety concerns related to the use of butanol or other chemicals, a water-based condensation particle counter (wCPC) has emerged to provide measurements under various environments. However, the airborne deployment of wCPC is relatively rare due to the lack of characterization of wCPC performance. This study investigates the performance of a commercial "versatile" water CPC (vWCPC Model 3789, TSI) under low-pressure conditions. The effect of conditioner temperature on wCPC performance at low pressure is examined through numerical simulation and laboratory experiments. We show that the default instrument temperature setting of 30 °C for the conditioner is not suitable for airborne measurement and that the optimal conditioner temperature for low-pressure operation is 27 °C. Additionally, we show that insufficient droplet growth becomes more significant under the low-pressure operation. The variation in the chemical composition can contribute up to 20 % uncertainty in the counting efficiency of the wCPC, but this variation is independent of pressure.