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At least 181 records · Page 10Linked to original sources

Physiological characterization of human ovarian cancer cells in a rat model of intraperitoneal antineoplastic therapy.

Destruction of cancer cells by therapies directed against new molecular targets requires their effective delivery to the tumor. To study diffusion and convection of intraperitoneal (ip) therapy to ip tumors, we established a new athymic rat (RNU) model with ovarian tumor cells (SKOV3 and OVCAR3) implanted in the abdominal wall. The model simulates metastatic tumor and facilitates the measurement of physiological parameters that govern transport forces. CD31 immunohistochemistry revealed unique patterns of angiogenesis, with a tissue-averaged vascular volume of approximately 0.01 ml/g for each tumor. The extracellular volume (SKOV3: 0.54 +/- 0.11 ml/g, n=5; OVCAR3: 0.61 +/- 0.03, n=5) was over twice that of the adjacent normal muscle (0.22 +/- 0.06 ml/g, n=5). Intravenous-injected antibody tumor clearance was two to three times that of muscle. Interstitial pressures were higher than normal tissue with a median of 10-15 mmHg. Quantitative autoradiography of frozen tissue slices from rats exposed to ip solutions containing [14C]mannitol or 125I-immunoglobulin G (trastuzumab) was performed to determine transport of small and large molecules. With ip pressure of 0-6 mmHg, both mannitol and immunoglobulin G displayed steep concentration profiles close to the tumor surface with limited penetration deeper within the tumor tissue; antibody penetration was significantly affected by ip pressure. These results demonstrated effects of molecular size, ip pressure, the limited but highly permeable tumor vasculature, and the expanded interstitium on drug penetration from the peritoneal cavity. In conclusion, we have characterized physical and chemical parameters that determine transport of therapeutic agents in our unique tumor-bearing rat model.

Animals↗

Modelling diffuse nutrient flow in eutrophication control scenarios.

The Swedish Water Management Research Programme (VASTRA) focuses on the development and demonstration of tools for more efficient eutrophication control when implementing the EU water framework directive in Sweden. During the first half of the programme, models for nitrogen flow were developed, and at present, similar models for phosphorus are under construction (e.g. HBV-P). The programme is interdisciplinary, and scientists are collaborating in actor-games and focus group evaluations including scenario analysis. The scenarios modelled in VASTRA phase I, show that (i) changed agricultural practices can be the most effective and least expensive way to reduce nitrogen transport from land to the sea; (ii) constructed agricultural wetlands may only have small impact on riverine nitrogen transport in some regions, due to natural hydrometeorological dynamics; (iii) removing planktivorous fish may be an efficient way of reducing the algal concentrations in lakes without the undesired side-effect of increased nutrient load to the down-stream river system. In VASTRA phase II, one of the highlights will be interdisciplinary scenario-modelling of different measure strategies in a pilot catchment of southern Sweden (Rönne å).

Agriculture↗

Prediction of pesticide concentrations in the atmosphere using an atmospheric diffusion model (linear source plume model).

The foundational model to predict concentration of pesticides in the atmosphere outside of the sprayed area was developed using the results of measured concentration in the atmosphere, in reference to the atmospheric diffusion model utilized for the air pollution prediction model. The atmospheric diffusion model assumes that the applied area was a topographically flat farmland, that wind direction and wind speeds were constant, and the pesticide was constantly discharged from the emission line sources. Therefore the linear source plume model (LSPLM) was developed. The concentration in the atmosphere was predicted by assigning the property of the pesticides and various conditions of measurements of the model, and compared with the measured them, then the adaptability of the model was examined. As a result, the correlation between the measured value and the predicted value in paddy and forested areas was significant (P < 0.01) although deviations in the order of tens were observed, the measured value and the predicted value were generally in agreement.

Agriculture↗

Cross-subject comparison of principal diffusion direction maps.

Diffusion tensor imaging (DTI) data differ fundamentally from most brain imaging data in that values at each voxel are not scalars but 3 x 3 positive definite matrices also called diffusion tensors. Frequently, investigators simplify the data analysis by reducing the tensor to a scalar, such as fractional anisotropy (FA). New statistical methods are needed for analyzing vector and tensor valued imaging data. A statistical model is proposed for the principal eigenvector of the diffusion tensor based on the bipolar Watson distribution. Methods are presented for computing mean direction and dispersion of a sample of directions and for testing whether two samples of directions (e.g., same voxel across two groups of subjects) have the same mean. False discovery rate theory is used to identify voxels for which the two-sample test is significant. These methods are illustrated in a DTI data set collected to study reading ability. It is shown that comparison of directions reveals differences in gross anatomic structure that are invisible to FA.

Algorithms↗

Aquaporin homologues in plants and mammals transport ammonia.

Using functional complementation and a yeast mutant deficient in ammonium (NH4+) transport (Deltamep1-3), three wheat (Triticum aestivum) TIP2 aquaporin homologues were isolated that restored the ability of the mutant to grow when 2 mM NH4+ was supplied as the sole nitrogen source. When expressed in Xenopus oocytes, TaTIP2;1 increased the uptake of NH4+ analogues methylammonium and formamide. Furthermore, expression of TaTIP2;1 increased acidification of the oocyte-bathing medium containing NH4+ in accordance with NH3 diffusion through the aquaporin. Homology modeling of TaTIP2;1 in combination with site directed mutagenesis suggested a new subgroup of NH3-transporting aquaporins here called aquaammoniaporins. Mammalian AQP8 sharing the aquaammoniaporin signature also complemented NH4+ transport deficiency in yeast.

Ammonia↗

Electrokinetics of diffuse soft interfaces. III. Interpretation of data on the polyacrylamide/water interface.

Streaming potential measurements were carried out on a family of polyacrylamide-co-sodium acrylate gels cross-linked with N,N'-methylenebisacrylamide in a homemade electrokinetic cell. Measurements of the ionic conductivity within thin films of these gels allowed the equilibrium Donnan potential difference between the bulk gel and the bulk electrolyte environments to be estimated at various ionic strengths. The resulting Donnan potential data were combined with the directly measurable streaming potential data and used to evaluate the diffuse soft interface model of electrokinetics (Langmuir 2004, 20, 10324). The model introduces the concept of a gradual decay of polymer density and fixed charge density within a narrow inter-phase at the gel/solution interface. The nature of the decay at the interface has a dramatic effect on the magnitude of the streaming potential as predicted by the diffuse soft interface model. In this investigation, the gradual decay of polymer density within the inter-phase is described with a hyperbolic tangent function. For the gels mentioned, the characteristic length scale of the decay, alpha, as calculated from the fit to the model, increases significantly with decreasing ionic strength, suggesting an osmotically driven swelling of the loosely cross-linked polymer chains at the interface. The experimental data and the results of the fitting are discussed in terms of the physical picture of the interface and compared to fitting results for a model which assumes a simple step function at the gel-solution interface.

Journal Article↗

In silico simulations reveal that replicators with limited dispersal evolve towards higher efficiency and fidelity.

The emergence of functional replicases, acting quickly and with high accuracy, was crucial to the origin of life. Although where the first RNA molecules came from is still unknown, it is nevertheless assumed that catalytic RNA enzymes (ribozymes) with replicase function emerged at some early stage of evolution. The fidelity of copying is especially important because the mutation load limits the length of replicating templates that can be maintained by natural selection. An increase in template length is disadvantageous for a fixed digit copying fidelity, however, longer molecules are expected to be better replicases. An iteration for longer molecules with better replicase function has been suggested and analysed mathematically. Here we show that more efficient replicases can spread, provided they are adsorbed to a prebiotic mineral surface. A cellular automaton simulation reveals that copying fidelity, replicase speed and template efficiency all increase with evolution, despite the presence of molecular parasites, essentially because of reciprocal atruism ('within-species mutualism') on the surface, thus making a gradual improvement of replicase function more plausible.

Adsorption↗

Broken symmetry and critical transport properties of random metals.

Recent experimental data on the conductivity final sigma+(T), T --> 0, on the metallic side of the metal-insulator transition in ideally random (neutron transmutation-doped) 70Ge:Ga have shown that final sigma+(0) ~ (N - Nc)mu with mu = (1/2), confirming earlier ultra-low-temperature results for Si:P. This value is inconsistent with theoretical predictions based on diffusive classical scaling models, but it can be understood by a quantum-directed percolative filamentary amplitude model in which electronic basis states exist which have a well-defined momentum parallel but not normal to the applied electric field. The model, which is based on a new kind of broken symmetry, also explains the anomalous sign reversal of the derivative of the temperature dependence in the critical regime.

Journal Article↗

Multitensor approach for analysis and tracking of complex fiber configurations.

A multidiffusion-tensor model (MDT) is presented containing two anisotropic and one isotropic diffusion tensors. This approach has the ability to detect areas of fiber crossings and resolve the direction of crossing fibers. The mean diffusivity and the ratio of the tensor compartments were merged to one independent parameter by fitting MDT to the diffusion-weighted intensities of a two-point data acquisition scheme. By an F-test between the errors of the standard single diffusion tensor and the more complex MDT, fiber crossings were detected and the more accurate model was chosen voxel by voxel. The performance of crossing detection was compared with the spherical harmonics approach in simulations as well as in vivo. Similar results were found in both methods. The MDT model, however, did not only detect crossings but also yielded the single fiber directions. The FACT algorithm and a probabilistic connectivity algorithm were extended to support the MDT model. For example, a mean angular error smaller than 10 degrees was found for the MDT model in a simulated fiber crossing with an SNR of 80. By tracking the corticospinal tract the MDT-based tracks reached a significantly greater area of the gyrus precentralis.

Algorithms↗

Mathematical model of TMA+ diffusion and prediction of light-dependent subretinal hydration in chick retina.

PURPOSE: To derive a mathematical model of TMA+ diffusion across the retina that can be used to estimate the amplitude and kinetics of the light-evoked increase in subretinal hydration and its effect on the concentration of other ions. METHODS: All experimental data were obtained in chick retina-pigment epithelium-choroid preparations as described in the accompanying paper. RESULTS: Diffusional properties of the retina were derived from the time course of [TMA+]o in the subretinal space (SRS) after changes in the retinal perfusate. Then, the SRS volume changes underlying the light-induced [TMA+]o response can be derived using a mathematical model of TMA+ diffusion. Complete retinal depth series of light-evoked [TMA+]o responses could be simulated by producing a corresponding expansion of the SRS. Volume changes inferred from the diffusion model were 2.2 to 3.8 times larger and more prolonged than could be derived directly from delta [TMA+]o. The model predicted up to a 20% peak increase in subretinal-space hydration during illumination. The effects of this volume increase on subretinal K+ and Ca2+ were estimated. These predictions were supported by inhibiting the volume increase with DIDS, which blocks retinal pigment epithelium basal membrane Cl- conductance. CONCLUSIONS: The primary source of light-evoked changes in extracellular TMA+ concentration recorded throughout the retina is an increase in hydration (volume) of the subretinal space. The response spreads to the inner retina by diffusion. Effects of TMA+ diffusion lead to large underestimates of the underlying volume changes. The light-evoked volume change alters the composition of the subretinal space and light-induced responses of other ions.

Animals↗

Axon shape as a basis for multinode functional units in a hierarchical neural model.

The ability of animals to perform fixed action patterns and to access information by categories suggests that there are several types of hierarchical organization in the nervous system. This paper employs data about axon shape and neurotransmitter effect to demonstrate the emergence of hierarchical structure in a neural model. Two dimensions of neural classification, axon shape and neurotransmitter effect, are used to generate a five-node-type neural model. Neurons are classified as interneurons, relay cells, and monoamine transmitters on the basis of axon shape; the transmitter classifications include excitatory, inhibitory, and parameter-changing. The five types of nodes in the model correspond to all the biologically observed combinations: excitatory and inhibitory short-range, excitatory and inhibitory long-range-directional, and long-lasting long-range-diffuse nodes. The emergence of multinode functional units (MFUs) from the five-node-type model is mathematically demonstrated. These units correspond to cortical columns anatomically defined by the axon fields of relay cells, and are called columnar multinode functional units (CMFUs). CMFUs may, in turn, be part of larger functional groups designated coherent populations, which consist of widely distributed CMFUs in retinotopically equivalent locations. The existence of coherent populations imposes a three-level hierarchical structure on the model. To represent this hierarchical structure, a new type of CMFU node, which has a set of vector-valued inputs and outputs, is introduced. Each CMFU node contains a system of short-range nodes which supplies it with vector-valued inputs. Sets of long-range-diffuse nodes are also treated as vector-valued nodes whose outputs control the size and number of coherent populations. The role of coherent populations and hierarchical organization in the nervous system is discussed for such cognitive tasks as visual perception, attention and learning. Physiological and behavioral evidence are cited which support the existence of a similar three-level hierarchy in vertebrate brains.

Animals↗

Anomalous photobleaching in fluorescence recovery after photobleaching measurements due to excitation saturation--a case study for fluorescein.

In this study we examine the implications of excitation saturation on fluorescence recovery after photobleaching (FRAP) experiments. In particular we present both experimental and theoretical evidence that fluorescein, one of the most frequently used fluorophores in FRAP, does not always comply with the basic assumptions that are made in many FRAP models: an invariant bleaching illumination intensity distribution (BID) in combination with first-order photobleaching kinetics. High light intensity levels, which are typical for the photobleaching phase of FRAP experiments, can cause excitation saturation of fluorescein in the excited triplet state. We show by experiments and computer simulations that under such saturating conditions the higher-order diffraction maxima of the BID substantially contribute to the photobleaching process and can no longer be neglected. As a result, the bleached regions are larger than expected theoretically from the FRAP models. Although this effect is not always directly evident from the FRAP experiments, neglecting it may shift the calculated diffusion coefficient by as much as over one order of magnitude. We present a discussion on the implications of this saturation effect on various types of FRAP models.

Algorithms↗

Modelling of Auger-induced DNA damage by incorporated 125I.

We have analyzed a newly available high resolution and precision repeat of the original Martin and Haseltine experiment which includes the influence of DMSO on the results. The new model includes the production and diffusion of radical species and .OH radical attack on DNA as well as the direct hits. Calculations of single-strand breaks use individual Auger electron along with the tracks of electrons and radical species superimposed on an atomistic model of B-DNA. Comparison of the preliminary calculations with the experiment supports the earlier choice of data for the amount of energy required to produce a single-strand break, i.e. 17.5 eV. In a separate simulation we found that an average of less than two ionizations inducing a single-strand break gave the best fit to experimental data. Direct hits were found to be predominantly occurring at short range while the damage by .OH radicals was mainly of the long-range type.

DNA, Single-Stranded↗

Statistical modelling of riverine nutrient sources and retention in the Lake Peipsi drainage basin.

Implementation of the Water Framework Directive calls for methodologies and tools to quantify nutrient losses from diffuse sources at a river basin district scale. Here, we examine the possibility of using a statistical model for source apportionment and retention of nutrients in a large transboundary drainage basin (44,000 km2). The model approach uses non-linear regression for simultaneous estimation of e.g. source strength, i.e. export coefficients to surface waters, for the different specified land-use or soil categories and retention coefficients for pollutants in a drainage basin. The model was tested on data from 26 water quality stations with corresponding sub-basin data, i.e., land cover, point sources and atmospheric deposition, from the Estonian part of the Lake Peipsi drainage basin. The model showed that it was statistically possible to derive reliable export coefficients (i.e. unit-area loads) for nitrogen on agricultural land and forests. Moreover, it was shown with simple empirical functions that lake retention was approximately 30-35% for both nitrogen and phosphorus and that the riverine retention was low for both nitrogen and phosphorus (approx. 10%). Results show that the MESAW model is a simple and powerful tool for simultaneous estimation of sources and retention of nutrient loads in a river basin.

Agriculture↗

Theoretical analysis of net tracer flux due to volume circulation in a membrane with pores of different sizes. Relation to solute drag model.

When osmotic pressure across an artificial membrane, produced by a permeable electrically neutral solute on one side of it, is balanced by an external pressure difference so that there is no net volume flow across the membrane, it has been found that there will be a net flux of a second electrically neutral tracer solute, present at equal concentrations on either side of the membrane, in the direction that the "osmotic" solute diffuses. This has been ascribed to solute-solute interaction or drag between the tracer and the osmotic solutes. An alternative model, presented here, considers the membrane to have pores of different sizes. Under general assumptions, this "heteroporous" model will account for both the direction of net tracer flux and the observed linear dependence of unidirectional tracer fluxes on the concentration of the osmotic solute. The expressions for the fluxes of solutes and solvent are mathematically identical under the two models. An inequality is derived which must be valid if the solute interaction model and/or the heteroporous model can account for the data. If the inequality does not hold, then the heteroporous model alone cannot explain the data. It was found that the inequality holds for most published observations except when dextran is the osmotic solute.

Cell Membrane Permeability↗

"Coarse" stability and bifurcation analysis using time-steppers: a reaction-diffusion example.

Evolutionary, pattern forming partial differential equations (PDEs) are often derived as limiting descriptions of microscopic, kinetic theory-based models of molecular processes (e.g., reaction and diffusion). The PDE dynamic behavior can be probed through direct simulation (time integration) or, more systematically, through stability/bifurcation calculations; time-stepper-based approaches, like the Recursive Projection Method [Shroff, G. M. & Keller, H. B. (1993) SIAM J. Numer. Anal. 30, 1099-1120] provide an attractive framework for the latter. We demonstrate an adaptation of this approach that allows for a direct, effective ("coarse") bifurcation analysis of microscopic, kinetic-based models; this is illustrated through a comparative study of the FitzHugh-Nagumo PDE and of a corresponding Lattice-Boltzmann model.

Computer Simulation↗

The finite element model for the propagation of light in scattering media: a direct method for domains with nonscattering regions.

We present a method for handling nonscattering regions within diffusing domains. The method develops from an iterative radiosity-diffusion approach using Green's functions that was computationally slow. Here we present an improved implementation using a finite element method (FEM) that is direct. The fundamental idea is to introduce extra equations into the standard diffusion FEM to represent nondiffusive light propagation across a nonscattering region. By appropriate mesh node ordering the computational time is not much greater than for diffusion alone. We compare results from this method with those from a discrete ordinate transport code, and with Monte Carlo calculations. The agreement is very good, and, in addition, our scheme allows us to easily model time-dependent and frequency domain problems.

Biophysical Phenomena↗

M5 mesoscopic and macroscopic models for mesenchymal motion.

In this paper mesoscopic (individual based) and macroscopic (population based) models for mesenchymal motion of cells in fibre networks are developed. Mesenchymal motion is a form of cellular movement that occurs in three-dimensions through tissues formed from fibre networks, for example the invasion of tumor metastases through collagen networks. The movement of cells is guided by the directionality of the network and in addition, the network is degraded by proteases. The main results of this paper are derivations of mesoscopic and macroscopic models for mesenchymal motion in a timely varying network tissue. The mesoscopic model is based on a transport equation for correlated random walk and the macroscopic model has the form of a drift-diffusion equation where the mean drift velocity is given by the mean orientation of the tissue and the diffusion tensor is given by the variance-covariance matrix of the tissue orientations. The transport equation as well as the drift-diffusion limit are coupled to a differential equation that describes the tissue changes explicitly, where we distinguish the cases of directed and undirected tissues. As a result the drift velocity and the diffusion tensor are timely varying. We discuss relations to existing models and possible applications.

Algorithms↗