External Concentration Research Articles

Computational Fluid Dynamics Modeling of Pressure-Retarded Osmosis: Towards a Virtual Lab for Osmotic-Driven Process Simulations

Pressure-Retarded Osmosis (PRO) is an osmotically driven membrane-based process that has recently garnered significant attention from researchers due to its potential for clean energy harvesting from salinity gradients. The complex interactions between mixed-mode channel flows and osmotic fluxes in real PRO membrane modules necessitate high-fidelity modeling approaches. In this work, an efficient CFD framework is developed for the 3D simulation of osmotically driven membrane processes. This approach is based on a two-way coupling between a CFD solver, which captures external concentration polarization (ECP) effects, and an analytical representation of internal concentration polarization (ICP). Consequently, the osmotic water flux and reverse salt flux (RSF) can be accurately determined, accounting for all CP effects without any limitations on the geometrical complexity of the membrane chamber or its flow mode/regime. The proposed model is validated against experimental data, showing good agreement across various PRO case studies. Additionally, the model’s flexibility to simulate other types of osmotically driven processes such as forward osmosis (FO) is examined. Thus, the contributions of ECP and ICP effects in local osmotic pressure drop along the membrane chamber are comprehensively compared for FO and PRO modes. Finally, the capability of the CFD model to simulate a lab-scale PRO module is demonstrated across a range of Reynolds numbers from low-speed laminar up to turbulent flow regimes.

The efflux system CdfX exports zinc that cannot be transported by ZntA in Cupriavidus metallidurans.

Cupriavidus metallidurans is able to survive exposure to high concentrations of transition metals, but is also able to grow under metal starvation conditions. A prerequisite of cellular zinc homeostasis is a flow equilibrium combining zinc uptake and efflux processes. The mutant strain ∆e4 of the parental plasmid-free strain AE104 with a deletion of all four chromosomally encoded genes of previously known efflux systems ZntA, CadA, DmeF, and FieF was still able to efflux zinc in a pulse-chase experiment, indicating the existence of a fifth efflux system. The gene cdfX, encoding a protein of the cation diffusion facilitator (CDF) family, is located in proximity to the cadA gene, encoding a P-type ATPase. Deletion of cdfX in the ∆e4 mutant resulted in a further decrease in zinc resistance. Pulse-chase experiments with radioactive 65Zn(II) and stable-isotope-enriched 67Zn(II) provided evidence that CdfX was responsible for the residual zinc efflux activity of the mutant strain ∆e4. Reporter gene fusions with cdfX-lacZ indicated that the MerR-type regulator ZntR, the main regulator of zntA expression, was responsible for zinc- and cadmium-dependent upregulation of cdfX expression, especially in mutant cells lacking one or both of the previously characterized efflux systems, ZntA and CadA. Expression of zntR also proved to be controlled by ZntR itself as well as by zinc and cadmium availability. These data indicate that the cdfX-cadA region provides C. metallidurans with a backup system for the zinc-cadmium-exporting P-type ATPase ZntA, with CdfX exporting zinc and CadA cadmium.IMPORTANCEBacteria have evolved the ability to supply the important trace element zinc to zinc-dependent proteins, despite external zinc concentrations varying over a wide range. Zinc homeostasis can be understood as adaptive layering of homeostatic systems, allowing coverage from extreme starvation to extreme resistance. Central to zinc homeostasis is a flow equilibrium of zinc comprising uptake and efflux reactions, which adjusts the cytoplasmic zinc content. This report describes what happens when an imbalance in zinc and cadmium concentrations impairs the central inner-membrane zinc efflux system for zinc by competitive inhibition for this exporter. The problem is solved by activation of Cd-exporting CadA or Zn-exporting CdfX as additional efflux systems.

Mutation of the K+ transporter SlHAK5 of tomato alters pistil morphology, ionome, metabolome and transcriptome in flowers.

K+ accumulation in plant tissues is a crucial factor for plant growth and development. The tomato high-affinity K+ transporter SlHAK5 is essential for root K+ acquisition from low external concentrations. It is also involved in K+ accumulation in pollen and plant fertility as slhak5 KO plants show a low rate of pollen germination, impaired pollen tube growth and parthenocarpic fruits. Here, we present a thorough analysis of slhak5 flowers, which showed relevant defects at the anatomic, ionomic, metabolomic and transcriptomic levels. First, slhak5 flowers exhibited shorter styles and enlarged ovaries that, together with a low number of seeds in fruits from slhak5 X WT crosses, indicated an effect of the slhak5 mutation on female fertility. Second, a lower accumulation of Ca2+, as well as of several metabolites such as amino acids, citric acid and sugars, was observed in mutant flowers, whereas indole-3-acetic acid content was increased when compared to the wild-type. Third, RNAseq conducted on pistils and stamens of wild-type and slhak5 plants revealed that transport and signalling pathways are significantly enriched in the gene expression analyses of stamens. Thus, it can be concluded that a functional SlHAK5 transporter is required to maintain appropriate Ca2+, metabolite and gene expression levels in flowers, and its absence leads to important reductions in both male and female fertility.

The Effect of Grain Boundary Misorientation on Hydrogen Flux Using a Phase‐Field‐Based Diffusion and Trapping Model

Understanding hydrogen–grain boundary (GB) interactions is critical to the analysis of hydrogen embrittlement in metals. This work presents a mesoscale fully kinetic model to investigate the effect of GB misorientation on hydrogen diffusion and trapping using phase‐field‐based representative volume elements (RVEs). The flux equation consists of three terms: a diffusive term and two terms for high and low angle grain boundary (H/LAGB) trapping. Uptake simulations show that decreasing the grain size results in higher hydrogen content due to increasing the GB density. Permeation simulations show that GBs are high‐flux paths due to their higher enrichment with hydrogen. Since HAGBs have higher enrichment than LAGBs, due to their higher trap‐binding energy, they generally have the highest hydrogen flux. Nevertheless, the flux shows a convoluted behavior as it depends on the local concentration, alignment of GB with external concentration gradient as well as the GB network connectivity. Finally, decreasing the grain size resulted in a larger break‐through time and a larger steady‐state exit flux.

Marine Amoebae‐Inspired Salting Hydrogels to Reconfigure Anisotropy for Reprogrammable Shape Morphing

Reprogrammable shape morphing is ubiquitous in living beings and highly crucial for them to move in normal situations, even to survive under dangerous conditions. There is increasing interest in using asymmetric hydrogel structures to understand and mimic living beings’ shape morphing upon an external trigger in a controlled way. However, these asymmetric or heterogeneous configurations cannot be further modified once the polymer hydrogels are prepared. Therefore, it is a great challenge to achieve reprogrammable shape morphing using the existing hydrogels. Inspired by marine amoebae, which transform into several different morphologies according to the various external salt concentrations, a new strategy is developed for salting hydrogels to reconfigure their anisotropy toward reprogrammable shape morphing. Polyampholyte hydrogels with equal stoichiometric COO‒ and N+(CH3)3 groups were first swollen in HCl/NaCl solution. After being then transferred into water, they first swollen again by water uptake driven by the osmotic pressure, and then were spontaneously deswollen due to increase in internal pH and dialysis of ions leading to deprotonation of COOH to COO‒ and regeneration of COO‒/N+(CH3)3 electrostatic attraction. This work provides a novel strategy to reconfigure anisotropy of hydrogel soft actuators and to open up an avenue for reprogrammable shape morphing.

Marine Amoebae-Inspired Salting Hydrogels to Reconfigure Anisotropy for Reprogrammable Shape Morphing.

Reprogrammable shape morphing is ubiquitous in living beings and highly crucial for them to move in normal situations, even to survive under dangerous conditions. There is increasing interest in using asymmetric hydrogel structures to understand and mimic living beings' shape morphing upon an external trigger in a controlled way. However, these asymmetric or heterogeneous configurations cannot be further modified once the polymer hydrogels are prepared. Therefore, it is a great challenge to achieve reprogrammable shape morphing using the existing hydrogels. Inspired by marine amoebae, which transform into several different morphologies according to the various external salt concentrations, a new strategy is developed for salting hydrogels to reconfigure their anisotropy toward reprogrammable shape morphing. Polyampholyte hydrogels with equal stoichiometric COO‒ and N+(CH3)3 groups were first swollen in HCl/NaCl solution. After being then transferred into water, they first swollen again by water uptake driven by the osmotic pressure, and then were spontaneously deswollen due to increase in internal pH and dialysis of ions leading to deprotonation of COOH to COO‒ and regeneration of COO‒/N+(CH3)3 electrostatic attraction. This work provides a novel strategy to reconfigure anisotropy of hydrogel soft actuators and to open up an avenue for reprogrammable shape morphing.

Radionuclides distribution in soils and radon level assessment in dwellings of Mungo and Nkam Divisions, Cameroon.

Radionuclide and radon levels have been investigated in soil samples and residential environments within the Mungo and Nkam Divisions of the Littoral Region. These analyses employed gamma spectrometry facilitated by a NaI (Tl) detector for soil samples, yielding average activity concentrations of 226Ra, 232Th, and 40K at 23.8, 72, and 105Bqkg-1, respectively. Various radiological parameters were calculated to evaluate radiological hazards. Additionally, the indoor radon concentrations were quantified utilizing the CR-39 solid-state nuclear track detector (Radtrack), revealing an average concentration of 25Bqm-3 and an associated inhalation dose of 0.66mSv y-1. Risk assessments for lung cancer attributable to indoor radon exposure incorporated models such as the Harley model. An observed moderate correlation between indoor radon levels and external 226Ra concentrations implies that radon intrusion indoors might be substantially influenced by the 226Ra present in the subjacent soil, considering the construction of residential structures directly upon these terrains.

Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.

Quetiapine is a second-generation atypical antipsychotic drug that has been commonly prescribed for the treatment of schizophrenia, major depressive disorder (depression), and other psychological disorders. Targeted inhibition of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels, which generate Ih, may provide effective resistance against schizophrenia and depression. We investigated if HCN channels could contribute to the therapeutic effect of quetiapine, and its major active metabolite norquetiapine. Two-electrode voltage clamp recordings were used to assess the effects of quetiapine and its active metabolites 7-hydroxyquetiapine and norquetiapine on currents from HCN1 channels expressed in Xenopus laevis oocytes. Norquetiapine, but not quetiapine nor 7-hydroxyquetiapine, has an inhibitory effect on HCN1 channels. Norquetiapine selectively inhibited HCN1 currents by shifting the voltage-dependence of activation to more hyperpolarized potentials in a concentration-dependent manner with an IC50 of 13.9 ± 0.8μM for HCN1 and slowing channel opening, without changing the kinetics of closing. Inhibition by norquetiapine primarily occurs from in the closed state. Norquetiapine inhibition is not sensitive to the external potassium concentration, and therefore, likely does not block the pore. Norquetiapine inhibition also does not dependent on the cyclic-nucleotide binding domain. Norquetiapine also inhibited HCN4 channels with reduced efficacy than HCN1 and had no effect on HCN2 channels. Therefore, HCN channels are key targets of norquetiapine, the primary active metabolite of quetiapine. These data help to explain the therapeutic mechanisms by which quetiapine aids in the treatment of anxiety, major depressive disorder, bipolar disorder, and schizophrenia, and may represent a novel structure for future drug design of HCN inhibitors.

Challenges of forward osmosis desalination processes using hydrogels as draw agents

The present study aims to investigate the properties, identification, and comprehension of the obstacles encountered in the forward osmosis process when utilizing a hydrogel drawing agent (FO-HG). Furthermore, a comparison is made between the FO-HG system and conventional forward osmosis systems employing a salt solution drawing agent. The comparison and evaluation of the swelling process of hydrogel and the kinetics of water penetration are conducted in both un-constrained and constrained states. Furthermore, the investigation and analysis are carried out to determine the presence or absence of internal concentration polarization (ICP) and external concentration polarization (ECP) phenomena. These phenomena are studied in situations with and without mixing, as well as in different orientations of the membrane (FO-mode and PRO-mode). The impact of these phenomena on the water flux of the systems FO-HG and FO-NaCl is also examined. An evaluation is conducted to determine the influence of the amount and size of hydrogel used as a draw agent in the FO-HG system on the water flux. The results of the study reveal that smaller hydrogel particles in the FO-HG system exhibit a higher flux compared to larger particles. Additionally, it is observed that the water flux in PRO-mode is unexpectedly higher when salt water is used as feed solution. This phenomenon can be ascribed to a counter-osmotic effect, originating from the FO state. Despite the high water absorption capacity of hydrogel and its potential as an ideal drawing agent in the forward osmosis process, the results demonstrate that the flux of the FO-HG system is inferior to that of the FO-NaCl system. Finally, the focus is on resolving the low flux issue by suggesting a process involving multiple cycles throughout day and night. We investigate the influence of hydrogel particle size, membrane surface, hydrogel layer thickness, as well as swelling and deswelling time in one cycle. The swelling time displays a peak at an optimal absorption duration, while the deswelling time does not show a similar optimal point, highlighting the difference between swelling and deswelling phenomena. Therefore, the hydrogels' high absorption capacity alone is insufficient for achieving desalination success. The research findings emphasize the high importance of synthesis of a membrane with minimal resistance, enabling a high water flux and suitable selectivity.

A proof-of-concept multi-tiered Bayesian approach for the integration of physiochemical properties and toxicokinetic time-course data for Daphnia magna

The use of in silico and in vitro methods, commonly referred to as New Approach Methodologies (NAMs), has been proposed to support environmental (and human) chemical safety decisions, ensuring enhanced environmental protection. Toxicokinetic models developed for environmentally relevant species are fundamental to the deployment of a NAMs-based safety strategy, enabling the conversion between external and internal chemical concentrations, although they require historical toxicokinetic data and robust physical models to be considered a viable solution. Daphnia magna is a key model organism in ecotoxicology albeit with limited and scattered quantitative toxicokinetic data, as for most invertebrates, resulting in a lack of robust toxicokinetic models. Moreover, current D. magna models are chemical specific, which restricts their applicability domain. One aim of this study was to address the current data availability limitations by collecting toxicokinetic time-course data for D. magna covering a broad chemical space and assessing the dataset's uniqueness. The collated toxicokinetic dataset included 48 time-courses for 30 chemicals from 17 studies, which was developed into an R package named AquaTK, with 11 studies unique to our work when compared to existing databases. Subsequently, a proof-of-concept Bayesian analysis was developed to estimate the steady-state concentration ratio (internal concentration / external concentration) from the data at three different levels of precision given three different data availability scenarios for environmental risk assessment. Specifically, an atrazine case study illustrates the multi-level modelling approach providing improvements (uncertainty reductions) in predictions of ratios for increasing amounts of data availability. Our work provides a consistent and self-contained Bayesian framework that irrespective of the hierarchy or resolution of individual experiments, can utilise the available information to generate optimal predictions of steady-state concentration ratios in D. magna. This approach is paramount to supporting the implementation of a NAMs based environmental safety paradigm shift in environmental risk assessment.

Distributed salinity sensor based on optical frequency domain reflectometry with polyimide coated single mode fiber

A distributed optical fiber sensor for salinity sensing is proposed and analyzed. The sensor uses a single mode fiber coated with polyimide and is based on optical frequency domain reflectometry. By applying the polyimide solution to the surface of the fiber, a layer of polyimide film is formed by heating. As the polyimide coating is very sensitive to changes in the salinity of the external solution, the polyimide film will expand or shrink as the external concentration changes. This converts the value of salt concentration into the frequency shift in the spectrum through cross-correlation. To characterize the sensor, four polyimide-coated sensors with different average coating thicknesses of 126 µm, 170 µm, 192 µm and 249 µm were fabricated. The sensitivities of -21.71 GHz/(mol/L), -28.55 GHz/(mol/L), -29.97 GHz/(mol/L) and -42.78 GHz/(mol/L) were achieved when the salinity was measured from 0 mol/L to 3.09 mol/L, respectively. The sensitivity and response time of polyimide fibers with different diameters were measured. The minimum salinity measurement uncertainty of the sensor is 0.05 mol/L. The sensor has high sensitivity and has promising applications in observing ocean parameters and ion chemical sensing.

Mathematical modeling of osmotic membrane bioreactor process for oily wastewater treatment

ABSTRACT To evaluate the disposal effluent from the Aldura refinery in Iraq, which comprises oily wastewater, a mathematical model has been developed for both forward osmosis (FO) and osmotic membrane bioreactor (OsMBR). The procedure is explained mathematically, accounting for both the concentration and polarization aspects. As a result of mathematical modeling, the water flux was determined by the osmotic pressure, the concentration, and the polarization of the feed and draw solutions. Based on traditional methods of predicting water flux using external and internal concentration polarizations, it is determined that water flux will occur in the first model (Model-1). To increase the accuracy of Model-1, the resistivity (K) of the solute has been modified to be independent of the diffusivity of the solute. The old model (Model-1) and the updated model (Model-2) overestimated water flux by 17 and 25%, respectively. It was possible to make a valid comparison between the experiment and theory based on the results of both experiments.

A gas sensing neural circuit for an olfactory neuron

A gas sensor can convert external gas concentration or species into electric voltage or current signals by physical adsorption or chemical changes. As a result, a gas sensor in a nonlinear circuit can be used as a sensitive sensor for detecting external gas signals from the olfactory system. In this paper, a gas sensor and a field-effect transistor are incorporated into a simple FithzHugh–Nagumo neural circuit for capturing and encoding external gas signals. An improved functional neural circuit is obtained, and the effect of gas concentration, gas species and neuronal activity can be discerned as the gate voltage, threshold voltage and activation coefficient of the field-effect transistor, respectively. The gas concentration can affect the neural activities from quiescent to normal working and, finally, to saturation state in bursting, spiking, periodic and chaotic firings with different frequencies. The effects of gas species and neuronal activity on the firing state can also be achieved in this functional neural circuit. In addition, variations in the gate voltage, threshold voltage and activation coefficient can cause switching between different firing modes. These results can be helpful in designing artificial olfactory devices for bionic gas recognition and other coupled systems arising in applied sciences.

Positional Information-Based Organization of Surfactant Droplet Swarms Emerging from Competition Between Local and Global Marangoni Effects.

Positional information is key for particles to adapt their behavior based on their position in external concentration gradients, and thereby self-organize into complex patterns. Here, position-dependent behavior of floating surfactant droplets that self-organize in a pH gradient is demonstrated, using the Marangoni effect to translate gradients of surface-active molecules into motion. First,fields of surfactant microliter-droplets are generated, in which droplets floating on water drive local, outbound Marangoni flows upon dissolution of surfactantand concomitantly grow myelin filaments. Next, a competing surfactant based on a hydrolysable amide is introduced, which is more surface active than the myelin surfactant and thereby inhibits the local Marangoni flows and myelin growth from the droplets. Upon introducing a pH gradient, the amide surfactant hydrolyses in the acidic region, so that the local Marangoni flows and myelin growth are reestablished. The resulting combination of local and global surface tension gradients produces a region of myelin-growing droplets and a region where myelin growth is suppressed, separated by a wave front of closely packed droplets, of which the position can be controlled by the pH gradient. Thereby, it is shown how "French flag"-patterns, in synthetic settings typically emerging from reaction-diffusion systems, can also be established via surfactant droplet systems.

Mechanics and thermodynamics of multivalent-binding induced shrinkage of hydrogels

Understanding the fundamental mechanism of shrink hydrogel sensors necessitates a complete comprehension of analyte-centered multivalent binding that occurs within their salt-rich microenvironments. However, the mechanics and thermodynamics governing this phenomenon remain insufficiently understood. Here, we aim to derive a theoretical framework that examines the impact of temporary cross-link formation on the hydrogel shrinkage due to specific binding interaction between the fixed receptors and the multivalent analytes. As a highlight of our theory, we mathematically quantify the hydrogels’ permanent and temporary cross-links using statistical thermodynamics to describe the multivalent complexation with different binding degrees while accounting for molecular-level transport factors when predicting the sensor’s shrinking characteristics. Consequently, our theory unveils the upper bounds set by the external analyte concentration and analyte binding valency onto the actuation sensitivity of these sensors, whereby tuning the receptor density permits further modulation of their performances. These findings tightly correlate the microscopic properties of the analyte and hydrogel to the macroscopic behaviors of shrink sensors, facilitating a structured design regime for advanced biomedical applications.

Methodology of integrated measurements with radon diffusion chamber

Calibration of Solid-State Nuclear Track Detectors - SSNTD in the diffusion chamber in most cases assumes a constant radon concentration outside the diffusion chamber and a steady state. Although this has been proven to be a valid approximation in most cases, the fact is that the radon concentration outside the chamber is not constant. In this way, the detectors are calibrated to measure the mean radon concentration. For this reason, there is doubt if the time-dependent concentration in dwellings results in the same number of tracks on the detector as the time-averaged radon concentration for the same exposure period. To obtain an answer, time-dependent and steady-state diffusion equations for radon and its progeny were solved. Then the number of tracks on the detector was calculated for these two cases and compared. For that goal, software for solving the time-dependent diffusion equation for time-varying external radon concentration was developed. Results show that concentrations measured using a diffusion chamber are the real concentrations at the measuring site. However, it was also found that the validity of results is not a universal property, as shown in the current paper. In some cases, results can be wrong. For some extreme conditions when diffusion coefficients are disrupted calibration using stationary conditions model will lead to incorrect results of real measurements in experiments where ambiental concentration is time-varying.

Understanding the influence of sodium chloride concentration on ion diffusion in charged polymers

Previous observations made on sulfonated polysulfones equilibrated with solutions of increasing salinity, where salt diffusion coefficients increase concurrently with reductions in water content driven by osmotic de-swelling, are currently unexplained. To further explain the molecular underpinnings of these observations, we characterized the influence of external salt solution concentration on the average salt and ion diffusion properties of two sulfonated polymers: a model cross-linked material (XLAMPS) and a series of sulfonated polysulfones (HQ:BP – XX). Analysis of the average salt and co- and counter-ion diffusion coefficients in these polymers suggest that the increase in charge screening (of electrostatic interactions between anionic sulfonate groups and co-ions) that occurs with increasing salinity affects the salt diffusion coefficients of sulfonated polysulfone in a manner that is different from what would be expected based on changes in water content alone and from what was observed for XLAMPS. Free volume theory describes the influence of these electrostatic effects on salt diffusion using a parameter related to the characteristic free volume element size necessary for diffusion. The results and analysis suggest that charge screening reduces the characteristic free volume element size necessary for diffusion in sulfonated polysulfone, which provides an explanation for the observed increase in average salt diffusion coefficients with increased salinity.

Length of Critical Streamers

The concept of equipotential length of positive quasi-stationary streamers is introduced as a criterion for assessing their degree of isolation. The equipotential length of positive critical streamers (streamers moving in the minimum electric field sufficient for the unrestricted propagation of a positive streamer) in the normal atmosphere is defined, both for individual streamers and those forming a thin bundle of streamers. The dependence of the equipotential length of positive quasi-stationary streamers on external field, velocity, radius, and electron concentration in the streamer head is investigated. A criterion is proposed for analytical models of quasi-stationary streamers, providing an additional independent equation to the system of equations describing the dynamics of quasi-stationary streamers, valid only for critical streamers. The insignificance of the influence of electrodes located at a distance greater than its equipotential length from the streamer head on the quasi-stationary streamer is proven, confirming the adequacy of using the equipotential length to assess the isolation of positive streamers.

PBPK model-based gender-specific risk assessment of N-nitrosodimethylamine (NDMA) using human biomonitoring data.

Despite several screening levels for NDMA reported in water, soil, air, and drugs, the human risk assessment using biomonitoring concentrations has not been performed. In this study, gender-specific exposure guidance values were determined in humans, then biomonitoring measurements in healthy Korean subjects (32 men and 40 women) were compared to the exposure guidance values to evaluate the current exposure level to NDMA. For the human risk assessment of NDMA, the gender-specific physiologically based pharmacokinetic (PBPK) model was developed in humans using proper physiological parameters, partition coefficients, and biochemical parameters. Using the PBPK model, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty on the single model predictions. The PBPK modeling and Monte Carlo simulation allowed the estimation of the relationship between external dose and blood concentration for the risk assessment. The procedure for the human risk assessment was summarized as follows: (1) estimating a steady-state blood concentration (Cavg) corresponding to the daily no observed adverse effect level (NOAEL) administration in rats; (2) applying uncertainty factors (UFs) for deriving the human Cavg; (3) determining the exposure guidance values as screening criteria; (4) interpreting the human biomonitoring measurements by forward and reverse dosimetry approaches. Using the biomonitoring concentrations, current daily exposures to NDMA were estimated to be 3.95μg/day/kg for men and 10.60μg/day/kg for women, respectively. The result of the study could be used as a basis for implementing further risk management and regulatory decision-making for NDMA.

Osmotic injury and cytotoxicity for hMSCs in contact with Me2SO: The effect of cell size distribution

The paper discusses the impact of cell size on cytotoxicity and expansion lysis during the osmotic excursions resulting from the contact of hMSCs from UCB with Me2SO. It builds upon the mathematical model recently presented by the authors, which pertains to a population of cells with uniform size. The objective is to enhance the model's relevance by incorporating the more realistic scenario of cell size distribution, utilizing a Population Balance Equations approach. The study compares the capability of the multiple-sized model to the single-sized one to describe system behavior experimentally measured through cytofluorimetry and Coulter counter when, first, suspending hMSCs in hypertonic solutions of Me2SO (at varying osmolality, system temperature, and contact times), and then (at room temperature) pelleting by centrifugation before suspending the cells back to isotonic conditions. Simulations demonstrate that expansion lysis and cytotoxic effect are not affected by cell size for the specific system hMSCs/Me2SO, thus confirming what was found so far by the authors through a single-size model. On the other hand, simulations show that, when varying the adjustable parameters of the model that are expected to change from cell to cell lineages, expansion lysis is sensitive to cell size, while cytotoxicity is not, being mainly influenced by external CPA concentration and contact duration. More specifically, it is found that smaller cells suffer expansion lysis more than larger ones. The findings suggest that different cells from hMSCs may require a multiple-sized model to assess cell damage during osmotic excursions in cryopreservation.