Molecular Transport Model Research Articles

Determining Rates of Molecular Secretion from Supernatant Concentration Measurements in a 3D-Bioprinted Human Liver Tissue Model.

The secretion rate of albumin is a key indicator of function in liver tissue models used for hepatotoxicity and pharmacokinetic testing. However, it is not generally clear how to determine molecular secretion rates from measurements of the molecular concentration in supernatant media. Here, we develop computational and analytical models of molecular transport in an experimental system that enable determination of albumin secretion rates based on measurements of albumin concentration in supernatant media. The experimental system is a 3D-bioprinted human liver tissue construct embedded in a 3D culture environment made from packed microgel particles swollen in liquid growth media. The mathematical models reveal that the range of albumin synthesis rates necessary to match experimentally measured albumin concentrations corresponds to reaction-limited conditions, where a steady state of albumin spatial distribution is rapidly reached between media exchanges. Our results show that temporally resolved synthesis rates can be inferred from serial concentration measurements of collected supernatant media. This link is critical to confidently assessing in vitro tissue performance in applications where critical quality attributes must be quantified, like in drug development and screening.

Benthic fluxes and mineralization processes at the scale of a coastal lagoon: Permeable versus fine-grained sediment contribution

Benthic fluxes of biogenic compounds play a major role in the biogeochemistry of shallow aquatic environments. Quantifying these fluxes at the scale of a lagoon is a challenge, especially when sediments are heterogeneous and fluxes at the sediment-water interface combine diffusive and advective transport processes. Diagenetic processes and associated benthic fluxes were quantified across different seasons in a lagoon of the French Mediterranean coast (La Palme lagoon) from vertical profiles of pore water and sedimentary solid fraction carried out at many representative stations of the lagoon. The northwestern part of the lagoon is covered with fine-grained sediment with low permeability and the rest of the lagoon contains permeable sandy sediment. We obtained vertical profiles with centimetre-scale resolution of water content, salinity, and major particulate and dissolved biogenic compounds of C, N, P, Si, S, Fe and Mn. This study allowed us to refine the sedimentary mapping of the lagoon, to specify the spatio-temporal evolution of biogeochemical processes, and to determine more precisely the part of the diffusive fluxes of nutrient compared to advective fluxes. Comparison of the vertical profiles with a molecular diffusion transport model shows that molecular diffusion is the dominant process in fine-grained sediments, while sandy sediments are dominated by advection due to circulation of lagoon water in shallow sediments. Benthic respiration renders fine-grained and sandy sediments anoxic from the first few mm below the sediment-water interface, particularly due to the availability of labile organic matter. Benthic dissolved inorganic nitrogen fluxes are of the same order of magnitude in both sediment types, despite the different flux mechanisms. This suggests that the intensity of organic matter mineralization processes is the same in fine and sandy sediments. Benthic phosphate fluxes are greater in sandy than in fine sediments because phosphorus is more efficiently retained in the solid fraction of fine sediments. Thus, sandy sediments play a dominant role in the pelagic-benthic coupling of the lagoon.

A Model of Thermally Activated Molecular Transport: Implementation in a Massive FPGA Cluster

In this paper, a massively parallel implementation of Boltzmann’s thermally activated molecular transport model is presented. This models allows taking into account potential energy barriers in molecular simulations and thus modeling thermally activated diffusion processes in liquids. The model is implemented as an extension to the basic Dynamic Lattice Liquid (DLL) algorithm on ARUZ, a massively parallel FPGA-based simulator located at BioNanoPark Lodz. The advantage of this approach is that it does not use any exponentiation operations, minimizing resource usage and allowing one to perform simulations containing up to 4,608,000 nodes.

Performance, energy and economic investigation of airgap membrane distillation system: An experimental and numerical investigation

Airgap membrane distillation (AGMD) is an efficient configuration employed widely for the solar membrane distillation desalination process. In the present work, 1-D Knudsen and molecular transport (KMT) model has been developed to investigate the performance of the flat sheet PVDF membrane. A new solution algorithm for the co-current and counter-current flow regime has been designed to solve the heat and mass transfer equations iteratively for a single-stage AGMD module. The feed temperature, feed flow rate, airgap size, salinity, membrane porosity and module length were varied and compared with experimental results. The increase in feed temperature from 40 °C to 80 °C resulted in 10.38 times increase in flux for co-current flow and 11.05 times for counter-current flow. The maximum permeate flux at 80 °C was 8.668 kg/m2h and 8.871 kg/m2h for the co-current and counter-current processes, respectively. Optimizing the feed temperature, flow rate, and membrane length using RSM suggests 80 °C, 1.528 LPM and 10 m as the optimum operating condition. An AGMD module of size 0.8 m width and 10 m length under the optimum operating condition exhibited a freshwater yield of 8.73 kg/h by consuming 24.98 kWh/m3 of specific energy, and the water production cost would be around $2.25/m3.

Influence of equivalence ratio on turbulent burning velocity and extreme fuel consumption rate in lean hydrogen-air turbulent flames

• The extreme fuel consumption rate (FCR) exhibits a high degree of universality. • The time-averaged extreme values are very close to the peak critically strained laminar flames. • This work supports a corner-stone hypothesis of the leading point concept of premixed turbulent burning. Unsteady three-dimensional Direct Numerical Simulations of seven statistically one-dimensional, planar, highly turbulent, complex-chemistry, lean H 2 -air flames are performed using either mixture averaged or equidiffusive model of molecular transport. The equivalence ratio is varied from 0.35 to 0.70 and the Karlovitz number Ka is varied from 3 to 565. Normalized turbulent burning velocities U T /S L are strongly increased when using the mixture-averaged model, with an increase by a factor of 4.1 being documented even at Ka as high as 565. Here, S L is the laminar flame speed. Moreover, the increase in U T /S L is significantly more pronounced in leaner flames, which are characterized by a thinner reaction zone and a larger Zel’dovich number. Furthermore, U T /S L is increased by the turbulence length scale. The extreme (maximum over the computational domain at a single instant) local values of fuel consumption rate (FCR) exhibit a high degree of universality, i.e., in all studied cases and at all instants, these rates are close to the peak values of FCR obtained from the counterpart critically strained, twin, counter-flow laminar premixed flames. This finding appears to directly support a corner-stone hypothesis of the leading point concept of premixed turbulent burning, thus, suggesting the use of characteristics of the critically strained laminar premixed flames as input parameters for models of turbulent combustion of lean H 2 /air mixtures.

A multiparametric advection-diffusion reduced-order model for molecular transport in scaffolds for osteoinduction

Scaffolds are microporous biocompatible structures that serve as material support for cells to proliferate, differentiate and form functional tissue. In particular, in the field of bone regeneration, insertion of scaffolds in a proper physiological environment is known to favour bone formation by releasing calcium ions, among others, triggering differentiation of mesenchymal cells into osteoblasts. Computational simulation of molecular distributions through scaffolds is a potential tool to study the scaffolds’ performance or optimal designs, to analyse their impact on cell differentiation, and also to move towards reduction in animal experimentation. Unfortunately, the required numerical models are often highly complex and computationally too costly to develop parametric studies. In this context, we propose a computational parametric reduced-order model to obtain the distribution of calcium ions in the interstitial fluid flowing through scaffolds, depending on several physical parameters. We use the well-known Proper Orthogonal Decomposition (POD) with two different variations: local POD and POD with quadratic approximations. Computations are performed using two realistic geometries based on a foamed and a 3D-printed scaffolds. The location of regions with high concentration of calcium in the numerical simulations is in fair agreement with regions of bone formation shown in experimental observations reported in the literature. Besides, reduced-order solutions accurately approximate the reference finite element solutions, with a significant decrease in the number of degrees of freedom, thus avoiding computationally expensive simulations, especially when performing a parametric analysis. The proposed reduced-order model is a competitive tool to assist the design of scaffolds in osteoinduction research.

A FEM Study of Molecular Transport Through a Single Nanopore in a Spherical Cell

Electroporation has a specific application in the delivery of drugs into the cells. In addition, the challenge is to be able to deliver the drugs effectively. The key to the electroporation-based delivery method is regulated induced transmembrane voltage (ITMV). Recently, with the advent of COVID-19, there has been an increase in clinical trials on the delivery of DNA plasmids by electroporation. As a result, the substantial number of laboratory experiments are not feasible, thereby increasing the dependency on simulation-based research. Simulations of delivery of extracellular material into the cell depend upon molecular transport modeling in an electroporated cell. In this paper, molecular transport through a single nanopore is being studied theoretically. The closed-form expression of molecular transport is used in COMSOL Multiphysics simulation to obtain extracellular concentration variation as a function of time. Sinusoidal pulses with the varying magnitude of electric field (8kV/cm and 10 kV/cm) and time duration were used to understand pulse parameters' effect on molecular transport. The simulation results match the empirical result from the literature hence validate the simulation study.

Experimental and numerical investigations on extinction strain rates in non-premixed counterflow methane and propane flames in an oxygen reduced environment

The aim of this work is to contribute to the better understanding of the oxidation process of light hydrocarbons, low calorific value gas and components of natural gas in the presence of inert gases and the influence of oxygen reduction in exhaust gas recirculation situations. The extinction behavior of laminar counterflow diffusion flames of methane (CH4), ethene (C2H4) and propane (C3H8) under nitrogen diluted condition has been investigated experimentally and numerically. In the experimental set-up, a counterflow burner was employed to investigate the extinction behavior under atmospheric conditions (1 bar and 298 K). The present study highlights the non-linear influence on the decrease in the extinction strain rate (ESR) that were found with decreasing fuel content and decreasing oxygen content. The oxygen content on the oxide side was stepwise diluted with nitrogen in order to distinctly show the possible oxygen-depleted influence in the recirculation areas. Additionally, it has been shown that the distance between the nozzles has an impact on the ESR but not on the general rising trend with the increasing fuel content in the non-premixed flames. Moreover, to clarify the influence, the flame zones were visualized using a system of high-speed OH* chemiluminescence camera. It was possible to investigate the width, intensity and position of the flame front from the radical detection. This provided a comprehensive data base for the subsequent numerical validation. In order to complement the experimental investigations, extensive uncertainty analyses were conducted and a new laser-based approach for the detection of flame extinction were demonstrated for the low-visible flames. Besides the experimental study, ESRs of CH4 and C3H8 combustion obtained from the experimental measurements were compared with those predicted by the numerical simulations. The San Diego-2014 reaction mechanism was used to represent the detailed chemical reaction, in which the predicted ESRs agree well with the experimental data was shown. Additionally, the effects of radiative heat loss, molecular transport model and chemical reactions on the ESRs were studied numerically. The present results suggest that the radiative heat loss plays a minor role on the ESRs, the molecular transport model is more significant and the ESRs are quite sensitive to several key reactions.

Phase transitions in two-channel TASEPs based on a new method of cluster mean-field analyses

A molecular motor transport model which is much closer to the actual situation is studied in this work. The two-chain totally asymmetric simple exclusion process (TASEP) with transverse and longitudinal binding energy is proposed, where particles transport in parallel. A new analytical method of cluster mean-field (CMF) analysis is proposed, which fully considers the boundary effects. The given new method of CMF is found to greatly improve the analytical accuracy of the traditional CMF and simple mean-field (SMF) analyses. Since the interactions among particles in the two channels are heavily considered, the state of the system is found to be sensitive to the change of external energy. Phase diagram and its evolution and the relationship between average density and total flux in the chain are found to be affected by the participation of energy. At the same time, a platform is found in the relationship curve reflecting total current versus average density. This relationship curve is also found to be symmetry to the average density 0.5. This paper presents a new system based on TASEPs in terms of the chain number and coupling binding energy. It will be conducive for proposing physical systems of real active systems and providing a new way for future research on real transport of molecular motors depicted by TASEPs.

The Concept of Cooperative Dynamics in Simulations of Soft Matter

In this review we compiled recent advances concerning the cooperative motion in crowded soft matter systems. We tried to answer the question how to perform dynamic Monte Carlo simulations of dense macromolecular systems effectively. This problem is not simple due to the fact that the movement in such systems is strictly correlated which leads to cooperative phenomena. The influence of crowding was found interesting especially for two-dimensional cases, e.g., in membranes where the presence of macromolecules, proteins and cytoskeleton often changed the mean-square displacement as a function of the lag time and anomalous diffusion appeared. Simple models are frequently used to shed a light on molecular transport in biological systems. The emphasis was given to the Dynamic Lattice Liquid model. The latter model became a basis for a parallel algorithm that takes into account coincidences of elementary molecular motion attempts resulting in local cooperative structural transformations. The emphasis is put on influence of the model of molecular transport on the diffusion. The comparison to alternative approaches like single agent model was carried out.

Stabilization mechanisms of CH4 premixed swirled flame enriched with a non-premixed hydrogen injection

High-fidelity Large Eddy Simulations (LES) are performed to study the effect of hydrogen injection on a lean turbulent CH4/Air premixed flame. An Analytically Reduced Chemistry (ARC) mechanism is used to achieve a detailed description of CH4/Air-H2 chemistry. First, a validation of this kinetic scheme against the detailed GRI-Mech 3.0 mechanism is presented considering both simplified and complex transport properties. When hydrogen is added to the mixture, large variations of the mixture Prandtl and of the N2 Schmidt numbers are observed depending on the local species concentrations, features that are missed by simplified models. LES is then applied to study the structure and stabilization mechanisms of a lean (ϕ = 0.8) premixed CH4/Air swirled flame enriched with hydrogen by using different transport modeling strategies. First, the fully premixed CH4/Air case is considered and results are found to validate the LES approach. In agreement with experiments, a classical V-shape flame is stabilized in the low-velocity region near the flame holder created by a central recirculation zone (CRZ). Then, hydrogen enrichment is achieved injecting 2% of the CH4 thermal power with a central fuel injection lance. Both premixed and diffusion flame branches are present in this case, impacting flame stabilization and flame angle. The flame root of the main premixed flame is stabilized by a diffusion flame kernel created by the injected hydrogen reacting with the oxygen in excess of the premixed stream. Moreover, the H2 consumed with the remaining oxygen in burnt gases leads to the formation of a second flame branch inside the CRZ which is responsible of an increase of the flame angle. Given the high concentration of hydrogen, an impact of the molecular transport models is observed on the flame lift-off height highlighting the importance of using complex transport properties in any LES involving hydrogen combustion.

Computational Model to Predict Tissue Concentration of Drugs Delivered via Intravital Fluid Exchange Devices

The microcirculation is capable of precise blood flow regulation enabling fine control over the distribution of oxygen (O2) to tissues in the body. The objective is to determine the role of capillaries in sensing and reporting local O2 concentration within tissue to upstream arterioles. It is hypothesized that red blood cells (RBCs) release ATP into the vessel lumen following O2 desaturation; ATP in the plasma binds to purinergic receptors on the endothelium triggering a signalling cascade that leads to a conducted vasodilatory response. Luminal application of ATP is known to initiate conducted dilation in arterioles yet whether or not this conducted response is present in capillaries has yet to be demonstrated.To investigate this mechanism of vascular control, we developed gas and liquid microfluidic devices for use in intravital video microscopy experiments to enable the local control of gases and agonists in skeletal muscle. These devices consist of a microfluidic flow channel interfaced with a glass slide with a laser cut micro‐outlet to allow exchange between the device and skeletal muscle during in vivo experiments. Experimentally, the gas exchange device was used to control the spatial distribution of O2 in the tissue to cause a highly localized hypoxic condition, to induce the release of ATP from RBCs. The liquid device was used to introduce ATP to a localized region of the capillary bed to stimulate ATP mediated mechanisms downstream. Further, we used acetylcholine (ACh) and phenylephrine (PE) as positive and negative controls, respectively. All animal protocols were approved by Memorial University’s Institutional Animal Care Committee.To quantify the local distribution of solutes in skeletal muscle we developed a transient, 3D transport model to predict the concentration of solutes applied experimentally in skeletal muscle. The transport equation was discretized and solved in parallel on a graphics processing unit. The computational model predicts highly localized spatial distributions of these solutes. As expected, the highest concentration of simulated solutes was at the surface of the tissue in contact with the exchange window, with steep decreases in concentration with increasing distance from the exchange window, falling by two orders of magnitude within 240 μm of the edge of the window in both the x and y directions, and by 300 μm in the z direction (see Fig. 1& 2). Logarithmic increases in applied drugs within the simulated microfluidic channel raise relative tissue concentrations proportionally. Predicted steady state concentrations of ACh, PE, and ATP varied due to the assumed rate of enzymatic degradation and efflux into the vasculature.In conclusion, our novel intravital video microscopy devices allow the exchange of gas and drugs to tissue to investigate the mechanisms of regulation in the microcirculation. Further, we quantified the localization of our devices using computational models of molecular transport, confirming the highly‐localized concentration gradients.Support or Funding InformationProject funded through NSERC Discovery Grant to GM Fraser.Tissue model results for 15 mmHg oxygen. The colour map shows the predicted tissue concentrations with 15 mmHg oxygen at the micro‐outlet. The top panel shows the gradients at the surface of the tissue closest to the gas‐based microfluidic device, in the x–y plane. The bottom panel illustrates the tissue partial pressure of oxygen perpendicular to the x–z plane centred at the middle of the micro‐outlet.Figure 1Tissue model results for adenosine triphosphate 10−4 M. The log scale colour map shows predicted tissue concentrations with 10−4 M adenosine triphosphate (ATP) at the micro‐outlet. The top panel shows the gradients at the surface of the tissue at the micro‐outlet. The bottom panel illustrates tissue ATP levels in the x–z plane centred on the micro‐outlet. ATP levels within the volume were above 3.47 × 10−7 M due to the initial assumption of blood ATP concentration.Figure 2

Effect of Moisture Sorption on Free Volume and Relaxation of Spray Dried Dispersions: Relation to Drug Recrystallization

The effect of vapor sorption on the free volume of drug-polymer spray-dried dispersions (SDDs) was investigated, along with the crystallization propensity of drug molecules in SDDs after exposure to humidity. Subsequently, the correlation of free volume change and relaxation time with drug recrystallization was examined. Four polymers, including polyvinylpyrrolidone, polyvinylpyrrolidone vinyl acetate copolymer, hydroxypropyl cellulose, and hydroxypropyl methylcellulose acetate succinate, and 2 drugs (indomethacin and ketoconazole) were selected for preparing SDDs. Free volume data of the exposed SDDs were obtained with positron annihilation lifetime spectroscopy, while the relaxation time was measured using a TA rheometer. Additionally, the crystallization propensity of active pharmaceutical ingredients (APIs) in the exposed SDDs was assessed using both polarized light microscopy and powder X-ray diffraction, followed by relating API crystallization inclination with expansion of holes and relaxation time. Finally, Cohen and Turnbull molecular transport model, along with its extensions by Vrentas and Duda, was qualitatively utilized for interpreting the recrystallization propensity of API molecules. In conclusion, API recrystallization is closely related to free volume change upon moisture sorption and relaxation time, but system dependent; overall, drug-hydroxypropyl methylcellulose acetate succinate SDDs appear physically stable against recrystallization due to less increase in free volume.

Molecular Transport through Self-Assembled DNA Nanofluidic Channels

Nanoscale channels are a fundamental mechanism for directed transport within living systems. Confinement of transport to one dimension makes transport rapid, and gating at channel entrances can make transport selective. However, little is known about the mechanisms and rates of transport of small molecules within nanoscale channels, particularly those that extend beyond the dimensions of lipid membranes and across hundreds of nanometers or microns. We have used techniques from structural DNA nanotechnology, which makes it possible to precisely control the geometry and chemical functionality of self-assembled structures, to construct synthetic nanoscale channels for molecular transport. The channel we have designed and constructed has an internal diameter of 4-6 nm and a length that can extend for multiple microns. It is composed of a DNA origami pore that penetrates and spans a lipid membrane and a DNA nanotube self-assembled from DAE-E double crossover tiles, consisting of five DNA oligomers that grows from the DNA origami pore. Membrane incorporation is facilitated by hydrophobic functionalization of DNA origami pore via 12 cholesterol moieties. These self-assembled channels can self-repair and can be grown such that their endpoints specifically attach at molecular landmarks, making them a promising biomolecular device for single-molecule biosensing, for studying intercellular signaling, and for drug delivery. We characterized molecular transport through these DNA channels by confocal microscopy and a dye influx assay, in which synthesized DNA channels spontaneously inserted onto giant unilamellar vesicles. The rates of fluorescent dye transport through the channels were quantified by time-lapse observation of intensities inside many vesicles through a confocal microscope and comparing to a diffusion-dominated molecular transport model. Our results indicate that transport of small molecules through these channels is diffusive and that molecule size determines the degree to which transport may occur.

Molecular transport in systems containing binding obstacles

We studied the movement of particles in crowded environments by means of extensive Monte Carlo simulations. The dynamic lattice liquid model was employed for this purpose. It is based on the cooperative movement concept and allows the study of systems at high densities. The cooperative model of molecular transport is assumed: the motion of all moving particles is highly correlated. The model is supposed to mimic lateral motion in a membrane and therefore the system is two-dimensional with moving objects and traps placed on a triangular lattice. In our study the interaction (binding) of traps with moving particles was assumed. The conditions in which subdiffusive motion appeared in the system were analysed. The influence of the strength of binding on the dynamic percolation threshold was also shown. The differences in the dynamics compared to systems with impenetrable obstacles and with systems without correlation in motion were presented and discussed. It was shown that in the case of correlated motion the influence of deep traps is similar to that of impenetrable obstacles. If the traps are shallow a recovery to normal diffusion was observed for longer time periods.

Simulations of a Turbulent Line Fire with a Steady Flamelet Combustion Model and Non-Gray Gas Radiation Models

The general objective of this project is to develop an accurate combustion and radiation modeling framework for high-fidelity large eddy simulations (LES) of well-controlled turbulent laboratory-scale fires for which the fuel composition and fuel oxidation chemistry are known. This modeling framework is aimed at providing a solid basis for the development and validation of engineering-level models used in simulations of real-world fire problems for which the sources of fuel are diverse, complex, and in many cases, poorly characterized. The combustion model features a library of flamelet solutions corresponding to one-dimensional, steady, laminar, counterflow diffusion flames simulated with specialized software, a chemical kinetic mechanism and an equi-diffusive molecular transport model (i.e., unity Lewis numbers). Two different flamelet libraries are considered here: a first library generated with a solver called libOpenSMOKE and a detailed chemical kinetic mechanism developed for C1-C3 combustion chemistry and a second library generated with a solver called FlameMaster and the GRI-Mech v3.0 chemical kinetic mechanism developed for methane combustion chemistry. The radiation model features a banded Weighted-Sum-of-Gray-Gases model but (so far) no description of subgrid-scale turbulence-radiation interactions (TRI). This modeling framework is incorporated into a LES solver developed by FM Global and called FireFOAM, and is evaluated in simulations of a two-dimensional, plane, buoyancy-driven, methane-air, turbulent diffusion flame experimentally studied at the University of Maryland. The configuration corresponds to an intermediate validation step in our model development strategy without the complications of flame extinction. The flame structure is characterized by new micro-thermocouple measurements of the temporal mean and root-mean-square gas temperatures. Comparisons between simulated and measured temperatures show significant discrepancies that are explained by the large values of the width of the presumed probability density function (PDF) representing subgrid-scale variations of mixture fraction and by the absence of a model for subgrid-scale TRI.

Numerical Model for Molecular and Particulate Contamination Transport

A new model for simulating molecular and particulate contamination transport is described. This model is implemented in the Contamination Transport Simulation Program (CTSP). The code uses techniques found in rarefied gas and plasma dynamics codes and represents the contaminants as simulation macroparticles. This kinetic approach allows the code to consider external forces and interparticle interactions. Macroscopic properties such as contaminant plume partial pressure can also be computed. CTSP implements various contamination-specific material sources including a detailed model for molecular outgassing and a model for particulate detachment. The code is demonstrated with four examples focusing on mass transport between two parallel plates, computation of the steady-state equilibrium in a closed vessel, characterization of a test article outgassing rate from a quartz crystal microbalance measurement, and the use of purge gas to reduce the particulate fallout in atmospheric conditions. Simulation results are compared to analytical models.

In vitro models of molecular and nano-particle transport across the blood-brain barrier.

The blood-brain barrier (BBB) is the tightest endothelial barrier in humans. Characterized by the presence of tight endothelial junctions and adherens junctions, the primary function of the BBB is to maintain brain homeostasis through the control of solute transit across the barrier. The specific features of this barrier make for unique modes of transport of solutes, nanoparticles, and cells across the BBB. Understanding the different routes of traffic adopted by each of these is therefore critical in the development of targeted therapies. In an attempt to move towards controlled experimental assays, multiple groups are now opting for the use of microfluidic systems. A comprehensive understanding of bio-transport processes across the BBB in microfluidic devices is therefore necessary to develop targeted and efficient therapies for a host of diseases ranging from neurological disorders to the spread of metastases in the brain.

Spiral waves and vertebrate embryonic handedness

During early embryonic development, the vertebrate main body axis is segmented from head-to-tail into somites. Somites emerge sequentially from the presomitic mesoderm (PSM) as a consequence of oscillatory waves of genetic activity, called somitogenesis waves. Here, we discuss the implications of the dynamic patterns of early X-Delta-2 expression in the prospective somites (somitomeres) of Xenopus laevis. We report that right somitomeres normally emerge before left to form chiral structures (i.e. structures having clockwise or counter-clockwise handedness). From our observations, we infer that somitogenesis waves are normally counter-clockwise spirals, a novel dynamic mechanism for the control of handedness development in Xenopus. We propose that the same mechanism could control handedness development in all vertebrate embryos, providing a dynamical basis for the current asymmetric molecular transport model for generating left-right asymmetry.

Breathable Vapor Toxicant Barriers Based on Multilayer Graphene Oxide.

There is tremendous interest in graphene-based membranes as protective molecular barriers or molecular sieves for separation technologies. Graphene oxide (GO) films in the dry state are known to be effective barriers for molecular transport and to expand in the presence of moisture to create enlarged intersheet gallery spaces that allow rapid water permeation. Here we explore an application for GO membranes as water-breathable barrier layers for personal protective equipment, which are designed to allow outward perspiration while protecting the wearer from chemical toxicants or biochemical agents in the local environment. A device was developed to measure permeation rates of small-molecular toxicants in the presence of counter-current water flow simulating active perspiration. The technique was applied to trichloroethylene (TCE) and benzene, which are important environmental toxicants, and ethanol as a limiting case to model very small, highly water-soluble organic molecules. Submicron GO membranes are shown to be effective TCE barriers, both in the presence and absence of simulated perspiration flux, and to outperform current barrier technologies. A molecular transport model is developed, which suggests the limited toxicant back-permeation observed occurs not by diffusion against the convective perspiration flow in hydrophobic channels, but rather through oxidized domains where hydrogen-bonding produces a near-stagnant water phase. Benzene and ethanol permeation fluxes are higher than those for TCE, likely reflecting the effects of higher water solubility and smaller minimum molecular dimension. Overall, GO films have high water breathability relative to competing technologies and are known to exclude most classes of target toxicants, including particles, bacteria, viruses, and macromolecules. The present results show good barrier performance for some very small-molecule species, but not others, with permeation being favored by high water solubility and small minimum molecular dimension.