Computational Model Of Transport Research Articles

Experimental and Computational Models of Transport of Galectin-3 Through Glycosylated Matrix.

Altered extracellular matrix (ECM) production is a hallmark of many fibroproliferative diseases, including certain cancers. The high incidence of glycan-rich components within altered ECM makes the use of glycan-binding proteins such as Galectin-3 (G3) a promising therapeutic strategy. The complexity of ECM as a rich 3D network of proteins with varied glycosylation states makes it challenging to determine the retention of glycan-binding proteins in altered ECM environments. Computational models capable of predicting the transport of glycan-binding proteins in altered ECM can benefit the design and testing of such proteins and associated novel therapeutic strategies. However, such computational models require many kinetic parameters that cannot be estimated from traditional 2D pharmacokinetic assays. To validate transport properties of G3 in 3D ECM constructs, we developed a species transport model that includes diffusion and matrix-binding components to predict retention of G3 fusion proteins in glycan-rich ECM. By iteratively comparing our computational model to experimental results, we are able to determine a reasonable range of parameters for a robust computational model of G3 transport. We anticipate this overall approach to building a data-driven model is translatable to other ECM-targeting therapeutic strategies.

TANDEM: biomicrofluidic systems with transverse and normal diffusional environments for multidirectional signaling.

Biomicrofluidic systems that can recapitulate complex biological processes with precisely controlled 3D geometries are a significant advancement from traditional 2D cultures. To this point, these systems have largely been limited to either laterally adjacent channels in a single plane or vertically stacked single-channel arrangements. As a result, lateral (or transverse) and vertical (or normal) diffusion have been isolated to their respective designs only, thus limiting potential access to nutrients and 3D communication that typifies in vivo microenvironments. Here we report a novel device architecture called "TANDEM", an acronym for "T̲ransverse A̲nd N̲ormal D̲iffusional E̲nvironments for M̲ultidirectional Signaling", which enables multiplanar arrangements of aligned channels where normal and transverse diffusion occur in tandem to facilitate multidirectional communication. We developed a computational transport model in COMSOL and tested diffusion and culture viability in one specific TANDEM configuration, and found that TANDEM systems demonstrated enhanced diffusion in comparison to single-plane counterparts. This resulted in improved viability of hydrogel-embedded cells, which typically suffer from a lack of sufficient nutrient access during long-term culture. Finally, we showed that TANDEM designs can be expanded to more complex alternative configurations depending on the needs of the end-user. Based on these findings, TANDEM designs can utilize multidirectional enhanced diffusion to improve long-term viability and ultimately facilitate more robust and more biomimetic microfluidic systems with increasingly more complex geometric layouts.

Computational Modeling of Transport in Porous Media Using an Adaptive Network-Based Fuzzy Inference System.

This investigation is conducted to study the integration of the artificial intelligence (AI) method with computational fluid dynamics (CFD). The case study is hydrodynamic and heat-transfer analyses of water flow in a metal foam tube under a constant wall heat flux (i.e., 55 kW/m2). The adaptive network-based fuzzy inference system (ANFIS) is an AI method. A 3D CFD model is established in ANSYS-FLUENT software. The velocity of the fluid in the x-direction (Ux) is considered as an output of the ANFIS. The x, y, and z coordinates of the node’s location are added to the ANFIS step-by-step to achieve the best intelligence. The number and type of membership functions (MFs) are changed in each step. The training process is done by the CFD results on the tube cross-sections at different lengths (i.e., z = 0.1, 0.2, 0.3, 0.4, 0.6, 0.7, 0.8, and 0.9), while all data (including z = 0.5) are selected for the testing process. The results showed that the ANFIS reaches the best intelligence with all three inputs, five MFs, and “gbellmf”-type MF. At this condition, the regression number is close to 1.

Impact of angiotensin II-mediated stimulation of sodium transporters in the nephron assessed by computational modeling.

Angiotensin II (ANG II) raises blood pressure partly by stimulating tubular Na+ reabsorption. The effects of ANG II on tubular Na+ transporters (i.e., channels, pumps, cotransporters, and exchangers) vary between short-term and long-term exposure. To better understand the physiological impact, we used a computational model of transport along the rat nephron to predict the effects of short- and long-term ANG II-induced transporter activation on Na+ and K+ reabsorption/secretion, and to compare measured and calculated excretion rates. Three days of ANG II infusion at 200 ng·kg-1·min-1 is nonpressor, yet stimulates transporter accumulation. The increase in abundance of Na+/H+ exchanger 3 (NHE3) or activated Na+-K+-2Cl- cotransporter-2 (NKCC2-P) predicted significant reductions in urinary Na+ excretion, yet there was no observed change in urine Na+. The lack of antinatriuresis, despite Na+ transporter accumulation, was supported by Li+ and creatinine clearance measurements, leading to the conclusion that 3-day nonpressor ANG II increases transporter abundance without proportional activation. Fourteen days of ANG II infusion at 400 ng·kg-1·min-1 raises blood pressure and increases Na+ transporter abundance along the distal nephron; proximal tubule and medullary loop transporters are decreased and urine Na+ and volume output are increased, evidence for pressure natriuresis. Simulations indicate that decreases in NHE3 and NKCC2-P contribute significantly to reducing Na+ reabsorption along the nephron and to pressure natriuresis. Our results also suggest that differential regulation of medullary (decrease) and cortical (increase) NKCC2-P is important to preserve K+ while minimizing Na+ retention during ANG II infusion. Lastly, our model indicates that accumulation of active Na+-Cl- cotransporter counteracts epithelial Na+ channel-induced urinary K+ loss.

Unified computational model of transport in metal-insulating oxide-metal systems

A unified physics-based model of electron transport in metal-insulator-metal (MIM) systems is presented. In this model, transport through metal-oxide interfaces occurs by electron tunneling between the metal electrodes and oxide defect states. Transport in the oxide bulk is dominated by hopping, modeled as a series of tunneling events that alter the electron occupancy of defect states. Electron transport in the oxide conduction band is treated by the drift–diffusion formalism and defect chemistry reactions link all the various transport mechanisms. It is shown that the current-limiting effect of the interface band offsets is a function of the defect vacancy concentration. These results provide insight into the underlying physical mechanisms of leakage currents in oxide-based capacitors and steady-state electron transport in resistive random access memory (ReRAM) MIM devices. Finally, an explanation of ReRAM bipolar switching behavior based on these results is proposed.

Advanced computational modeling for in vitro nanomaterial dosimetry.

BackgroundAccurate and meaningful dose metrics are a basic requirement for in vitro screening to assess potential health risks of engineered nanomaterials (ENMs). Correctly and consistently quantifying what cells “see,” during an in vitro exposure requires standardized preparation of stable ENM suspensions, accurate characterizatoin of agglomerate sizes and effective densities, and predictive modeling of mass transport. Earlier transport models provided a marked improvement over administered concentration or total mass, but included assumptions that could produce sizable inaccuracies, most notably that all particles at the bottom of the well are adsorbed or taken up by cells, which would drive transport downward, resulting in overestimation of deposition.MethodsHere we present development, validation and results of two robust computational transport models. Both three-dimensional computational fluid dynamics (CFD) and a newly-developed one-dimensional Distorted Grid (DG) model were used to estimate delivered dose metrics for industry-relevant metal oxide ENMs suspended in culture media. Both models allow simultaneous modeling of full size distributions for polydisperse ENM suspensions, and provide deposition metrics as well as concentration metrics over the extent of the well. The DG model also emulates the biokinetics at the particle-cell interface using a Langmuir isotherm, governed by a user-defined dissociation constant, KD, and allows modeling of ENM dissolution over time.ResultsDose metrics predicted by the two models were in remarkably close agreement. The DG model was also validated by quantitative analysis of flash-frozen, cryosectioned columns of ENM suspensions. Results of simulations based on agglomerate size distributions differed substantially from those obtained using mean sizes. The effect of cellular adsorption on delivered dose was negligible for KD values consistent with non-specific binding (> 1 nM), whereas smaller values (≤ 1 nM) typical of specific high-affinity binding resulted in faster and eventual complete deposition of material.ConclusionsThe advanced models presented provide practical and robust tools for obtaining accurate dose metrics and concentration profiles across the well, for high-throughput screening of ENMs. The DG model allows rapid modeling that accommodates polydispersity, dissolution, and adsorption. Result of adsorption studies suggest that a reflective lower boundary condition is appropriate for modeling most in vitro ENM exposures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-015-0109-1) contains supplementary material, which is available to authorized users.

Quantification of Lacunar-Canalicular Interstitial Fluid Flow Through Computational Modeling of Fluorescence Recovery After Photobleaching.

Skeletal adaptation to mechanical loading has been widely hypothesized to involve the stimulation of osteocytes by interstitial fluid flow (IFF). However, direct investigation of this hypothesis has been difficult due in large part to the inability to directly measure IFF velocities within the lacunar-canalicular system. Measurements of fluorescence recovery after photobleaching (FRAP) within individual lacunae could be used to quantify lacunar-canalicular IFF when combined with mathematical modeling. In this study, we used a computational transport model to characterize the relationship between flow frequency (0.5-10 Hz), peak flow velocity (0-300 μm/s), tracer diffusion coefficient (100-300 μm(2)/s), and transport enhancement (i.e., (k/k(0)) - 1, where k and k(0) are the transport rates in the presence/absence of flow) during lacunar FRAP investigations. We show that this relationship is well described by a simple power law with frequency-dependent coefficients, and is relatively insensitive to variations in lacunar geometry. Using this power law relationship, we estimated peak IFF velocities in hindlimb mice subjected to intramedullary pressurization using values of k and k(0) previously obtained from ex vivo lacunar FRAP investigations. Together, our findings suggest that skeletal adaptation in hindlimb suspended mice subjected to dynamic intramedullary pressure occurred in the presence of IFF at levels associated with physiological loading.

Condensational Growth May Contribute to the Enhanced Deposition of Cigarette Smoke Particles in the Upper Respiratory Tract

Previous experimental studies have shown that concentrated cigarette smoke particles (CSPs) deposit in the upper airways like much larger 6 to 7 μ m aerosols. Based on the frequent assumption that relative humidity (RH) in the lungs does not exceed approximately 99.5%, the hygroscopic growth of initially submicrometer CSPs is expected to be a relatively minor factor. However, the inhalation of mainstream smoke may result in humidity values ranging from sub-saturated through supersaturated conditions. The objective of this study is to evaluate the effect of condensation particle growth on the transport and deposition of CSPs in the upper respiratory tract under various RH and temperature conditions. To achieve this objective, a computational model of transport in the continuous phase surrounding a CSP was developed for a multicomponent aerosol consisting of water soluble and insoluble species. To evaluate the transport and deposition of dilute hygroscopic CSPs in the upper airways, a model of the human mou...

Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI

Convection-enhanced delivery (CED), that is, direct tissue infusion, has emerged as a promising local drug delivery method for treating diseases of the nervous system. Determination of the spatial distribution of therapeutic agents after infusion is important in evaluating the efficacy of treatment, optimizing infusion protocols and improving the understanding of drug pharmacokinetics. In this study, we provide a methodology to determine the concentration distribution of Gd-labeled tracers during infusion using contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, MR studies that quantify concentration profiles for CED have not been previously reported. The methodology utilizes intrinsic material properties (T(1) and R(1)) and reduces the effect of instrumental factors (e.g., inhomogeneity of MR detection field). As a methodology investigation, this study used an agarose hydrogel phantom as a tissue substitute for infusion. An 11.1-T magnet system was used to image infusion of Gd-DTPA-labeled albumin (Gd-albumin) into the hydrogel. By using data from preliminary scans, Gd-albumin distribution was determined from the signal intensity of the MR images. As a validation test, MR-derived concentration profiles were found comparable to both results measured directly using quantitative optical imaging and results from a computational transport model in porous media. In future studies, the developed methodology will be used to quantitatively monitor the distribution of Gd tracer following infusion directly into tissues.

A Computational Transport Model for Wall-Cooled Catalytic Reactor

A computational transport model is proposed for simulating the concentration, temperature, and velocity distributions in a wall-cooled fixed-bed catalytic reactor producing vinyl acetate from acetic acid and acetylene without assuming empirical Sct and Prt numbers or using the experimental coefficient of dispersion. The model consists of the basic differential equation of mass transfer with the recently developed− εc model for its closure and the accompanied computational fluid dynamics and heat transfer models. With the present model, the radial and axial profiles of turbulent mass-transfer diffusivity Dt, turbulent thermal diffusivity αt, and turbulent kinematic viscosity νt, as well as their distributions in the reactor are obtained. It is found that the local ratios of νt/Dt and νt/αt, or the local Prandtl (Prt) and Schmidt (Sct) numbers, are varying in the reactor, although the shapes of the νt, αt, and Dt profiles show somewhat similarity. The simulated results are found to be in agreement with the experimental measurements reported by Valstar et al.33

Continuum transport model of Ogston sieving in patterned nanofilter arrays for separation of rod‐like biomolecules

This article proposes a simple computational transport model of rod-like short dsDNA molecules through a microfabricated nanofilter array. Using a nanochannel consisting of alternate deep wells and shallow slits, it is demonstrated that the complex partitioning of rod-like DNA molecules of different sizes over the nanofilter array can be well described by continuum transport theory with the orientational entropy and anisotropic transport parameters properly quantified. In this model, orientational entropy of the rod-like DNA is calculated from the equilibrium distribution of rigid cylindrical rod near the solid wall. The flux caused by entropic differences is derived from the interaction between the DNA rods and the solid channel wall during rotational diffusion. In addition to its role as an entropic barrier, the confinement of the DNA in the shallow channels also induces large changes in the effective electrophoretic mobility for longer molecules in the presence of EOF. In addition to the partitioning/selectivity of DNA molecules by the nanofilter, this model can also be used to estimate the dispersion of separated peaks. It allows for fast optimization of nanofilter separation devices, without the need of stochastic modeling techniques that are usually required.

Transport modeling in ionomeric polymer transducers and its relationship to electromechanical coupling

Ionomeric polymer transducers consist of an ion-conducting membrane sandwiched between two metal electrodes. Application of a low voltage (<5V) to the polymer produces relatively large bending deformation (>2% strain) due to the transport of ionic species within the polymer matrix. A computational model of transport and electromechanical transduction is developed for ionomeric polymer transducers. The transport model is based upon a coupled chemoelectrical multifield formulation and computes the spatiotemporal volumetric charge density profile to an applied potential at the boundaries. The current induced in the polymer is computed using the isothermal transient ionic current associated with surface charge accumulation at the electrodes induced by nonzero volumetric charge density within the polymer. The stress induced in the polymer is assumed to be a summation of linear and quadratic functions of the volumetric charge density. Euler-Bernoulli beam mechanics are used to compute the bending deflection of the transducer to an applied potential. The diffusion coefficient and permittivity of the polymer is identified from the measured current density to a step change in the applied potential. A comparison between the measured data and the predicted response demonstrates that this model accurately predicts the current discharge due to the applied potential at voltages over the range of 50–500mV. Furthermore, the measured strain response is accurately predicted by determining the two parameters of the mechanics model that relates volumetric charge density to induced stress. The coupled model with parameters identified from the step response analysis is used to predict the harmonic response of the current and the bending strain. Comparisons between measured data and simulations illustrate that the coupled transport-mechanics model accurately predicts the magnitude and trends associated with the current response and strain output. Excellent agreement is obtained at excitation periods above approximately 1s while good agreement is obtained at longer excitation periods. The transport model highlights the importance of the asymmetry that develops at large applied potentials and long excitation periods in the volumetric charge density due to the fixed anionic species in the polymer.

Physical stresses at the air-wall interface of the human nasal cavity during breathing

The nose is the front line defender of the respiratory system and is rich with mechanoreceptors, thermoreceptors, and nerve endings. A time-dependent computational model of transport through nasal models of a healthy human has been used to analyze the fields of physical stresses that may develop at the air-wall interface of the nasal mucosa. Simulations during quiet breathing revealed wall shear stresses as high as 0.3 Pa in the noselike model and 1.5 Pa in the anatomical model. These values are of the same order of those known to exist in uniform large arteries. The distribution of temperature near the nasal wall at peak inspiration is similar to that of wall shear stresses. The lowest temperatures occur in the vicinity of high stresses due to the narrow passageway in these locations. Time and spatial gradients of these stresses may have functional effects on nasal sensation of airflow and may play a role in the well-being of nasal breathing.

The character of transport caused by E×B drift turbulence

The basic character of diffusive transport in a magnetized plasma depends on what kind of transport is modeled. E×B turbulence under drift ordering has special characteristics: it is nearly incompressible, and it cannot lead to magnetic flux diffusion if it is electrostatic. The E×B velocity is also related to the Poynting energy flux. Under quasineutral dynamics, electric fields are not caused by transport of electric charge but by the requirement that the total current is divergence free. Consequences for well constructed computational transport models are discussed in the context of a general mean field analysis, which also yields several anomalous transfer mechanisms not normally considered by current models.