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PubMedDate not supplied

Temperature mapping of laser-induced hyperthermia in an ocular phantom using magnetic resonance thermography.

Laser-induced heating in an ocular phantom is measured with magnetic resonance thermography (MRT) using temperature-dependent phase changes in proton resonance frequency. The ocular phantom contains a layer of melanosomes isolated from bovine retinal pigment epithelium. The phantom is heated by the 806-nm output of a continuous wave diode laser with an irradiance of 2.4 to 21.6 W/cm2 in a beam radius of 0.8 or 2.4 mm, depending on the experiment. MRT is performed with a 2 T magnet, and a two-turn, 6-cm-diam, circular radio frequency coil. Two-dimensional temperature gradients are measured within the plane of the melanin layer, as well as normal to it, with a temperature resolution of 1 degrees C or better. The temperature gradients extending within the melanin layer are broader than those orthogonal to the layer, consistent with the higher optical absorption and consequent heating in the melanin. The temperature gradients in the phantom measured by MRT closely approximate the predictions of a classical heat diffusion model. Three-dimensional temperature maps with a spatial resolution of 0.25 mm in all directions are also made. Although the temporal resolution is limited in the prototype system (22.9 s for a single image "slice"), improvements in future implementations are likely. These results indicate that MRT has sufficient spatial and temperature resolution to monitor target tissue temperature during transpupillary thermotherapy in the human eye.

Animals↗
PubMed1994

Direct observation of tube-like motion of a single polymer chain.

Tube-like motion of a single, fluorescently labeled molecule of DNA in an entangled solution of unlabeled lambda-phage DNA molecules was observed by fluorescence microscopy. One end of a 16- to 100-micrometer-long DNA was attached to a 1-micrometer bead and moved with optical tweezers. The molecule was stretched into various conformations having bends, kinks, and loops. As the polymer relaxed, it closely followed a path defined by its initial contour. The relaxation time of the disturbance caused by the bead was roughly 1 second, whereas tube-like motion in small loops persisted for longer than 2 minutes. Tube deformation, constraint release, and excess chain segment diffusion were also observed. These observations provide direct evidence for several key assumptions in the reptation model developed by de Gennes, Edwards, and Doi.

Bacteriophage lambda↗
PubMedDate not supplied

[Asymptotic solution of the model of the erythrocyte shape as an autowave process].

An asymptotic solution was plotted for a model of erythrocyte forms assuming that the biomembrane is anisotropic and of "small" thickness. This leads to small non-linearity and low diffusion, therefore the solution is unrelaxational. The model was investigated qualitatively assuming that the liquid current directed inside the spheric membrane induces its "distension", while that directed outside-its "crumpling". In the spherical system of coordinates the lines of solution level at theta = const are circumferences, while at phi-const-trochoids (Pascal coil, for example). Trochoids rotation areas show stomacyte and discocyte forms. Several hypotheses based on the analysis performed are advanced.

Erythrocyte Membrane↗
PubMed1991

Stromal regulation of epithelial function.

Stromal influences upon epithelia are part of a continuum of cellular interactions that begins at fertilization and extends into adulthood. In parenchymal organs, the most thoroughly characterized interactions have been those that occur during development between mesenchyme, embryonic stroma, and epithelium. Mesenchyme is essential for epithelial proliferation, morphogenesis, and differentiation. Hormones affect stromal-epithelial interactions, and in some cases, steroid hormones may produce their effects on the epithelium indirectly, acting via the mesenchyme. In many adult organs the epithelia continually proliferate and differentiate and consequently may be considered developing systems within the mature organism. This is especially true in organs with a rapidly renewing epithelium, such as the intestine, and in organs that have cycles of functional activity, such as those of the female reproductive system. The mechanisms by which stroma affects epithelial structure and function are not well understood. Current models of how signaling may be accomplished include transmission via diffusible substances, via the extracellular matrix (ECM), and via direct cell-cell contact. Growth factors and organ-specific paracrine factors are candidates for stromal cues that affect the epithelium in some systems. Components of the ECM appear to play a role in permissive interactions and may affect epithelial function by changing cell shape or by binding ECM to the cell surface integrin receptors. Signaling via direct stromal-epithelial contact may be accomplished via interactions between complimentary cell surface adhesion molecules. The importance of stromal-epithelial interactions is reemphasized by several models of carcinogenesis that suggest that perturbations in these interactions may be involved in tumor progression.

Adult↗
PubMed2005

Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.

PURPOSE: Ischemia/reperfusion injury is a leading cause of renal damage and antisense gene therapy has been shown to ameliorate its effects. However, this approach has been limited by current delivery methods that require high concentrations of intravenous nucleic acids lacking specificity for targeting tissues. To overcome these limitations we developed a novel murine partial nephrectomy model to evaluate polyethylene-glycol (PEG) hydrogel tissue sealant as a topical oligonucleotide delivery system. MATERIALS AND METHODS: A total of 18 male C57BL/6 mice underwent left partial nephrectomy with vascular occlusion. Hydrogel primer and then sealant were applied to the cut surface and photopolymerized. Using this method 16 additional mice received hydrogel primer mixed with Cy5 labeled fluorescent oligonucleotide (10 to 100 microg). Kidneys were harvested at various time points and assessed for oligonucleotide penetration using fluorescence microscopy. RESULTS: A survival rate of 100% (34 subjects) was obtained using this mouse model of partial nephrectomy. PEG hydrogel provided adequate protection against renal hematoma and intraperitoneal blood. Fluorescent images revealed that 50 microg was the minimum dose resulting in complete progressive cellular penetration with time. In addition to direct diffusion from the application site, movement of oligonucleotide through the subcapsular space into the cortex was an observed mechanism of distribution. CONCLUSIONS: A murine partial nephrectomy model was successfully created using PEG hydrogel. In addition to achieving hemostasis, hydrogel served as a successful depot for delivering oligonucleotides throughout the kidney.

Animals↗
PubMed2002

Transepithelial ultrafiltration and fractal power diffusion of D-glucose in the perfused rat intestine.

Despite an enormous body of research investigating the mass transfer of D-glucose through biological membranes, carrier-mediated and first-order models have remained the prevalent models describing glucose's quantitative behavior even though they have proven to be inadequate over extended concentration ranges. Recent evidence from GLUT2 knockout studies further questions our understanding of molecular models, especially those employing Michaelis-Menten (MM)-type kinetic models. In this report, evidence is provided that D-glucose is absorbed by rat intestinal epithelium by a combination of convective ultrafiltration and nonlinear diffusion. The diffusive component of mass transfer is described by a concentration-dependent permeability coefficient, modeled as a fractal power function. Glucose and sodium chloride-dependent-induced aqueous convection currents are the result of prevailing oncotic and osmotic pressure effects, and a direct effect of glucose and sodium chloride on intestinal epithelium resulting in enhanced glucose, sodium ion, and water mobility. The fractal power model of glucose diffusion was superior to the conventional MM description. A convection-diffusion model of mass transfer adequately characterized glucose mass transfer over a 105-fold glucose concentration range in the presence and absence of sodium ion.

Animals↗
PubMed1991

A new view of convective-diffusive transport processes in the arterial intima.

In this paper a new theoretical framework is presented for analyzing the filtration and macromolecular convective-diffusive transport processes in the intimal region of an artery wall with widely dispersed macromolecular cellular leakage sites, as proposed in the leaky junction-cell turnover hypothesis of Weinbaum et al. In contrast to existing convection-diffusive models, which assume that the transport is either 1-D, or convection is primarily in a direction normal to the endothelial surface, the present model considers for the first time the nonuniform subendothelial pressure field that arises from the different hydraulic resistances of normal and leaky endothelial clefts and the special role of the internal elastic lamina (IEL) in modulating the horizontal transport of macromolecules after they have passed through the leaky clefts of cells that are either in mitosis or demonstrate IgG labeling. The new theory is able to quantitatively explain the growing body of recent experiments in which an unexpectedly rapid early-time growth of the leakage spot has been observed and the longer time asymptotic behavior in which the leakage spot appears to approach an equilibrium diameter. The new theory also predicts the observed doubling in macromolecular permeability between EBA labeled blue and white areas when the frequency of leakage sites is doubled. This frequency for doubling of permeability, however, is an order of magnitude smaller than predicted by the author's previous model, Tzeghai et al., in which only convection normal to the endothelial surface was considered and the pressure was uniform in the intima. The longer time model predictions are used to explain the time scale for the formation of liposomes in subendothelial tissue matrix in animal feeding experiments where it has been observed that the extracellular lipid concentration rises sharply prior to the entry of monocytes into the intima.

Arteries↗
PubMed1999

Zebrafish angiogenesis: a new model for drug screening.

Angiogenesis is necessary for tumor growth, making inhibition of vessel formation an excellent target for cancer therapy. Current assays for angiogenesis, however, are too complex to be practical for drug screening. Here, we demonstrate that the zebrafish is a viable whole animal model for screening small molecules that affect blood vessel formation. Blood vessel patterning is highly characteristic in the developing zebrafish embryo and the subintestinal vessels (SIVs) can be stained and visualized microscopically as a primary screen for compounds that affect angiogenesis. Small molecules added directly to the fish culture media diffuse into the embryo and induce observable, dose-dependent effects. To evaluate the zebrafish as a model, we used two angiogenesis inhibitors, SU5416 and TNP470, both of which have been tested in mammalian systems. Both compounds caused a reduction in vessel formation when introduced to zebrafish embryos prior to the onset of angiogenesis. Short duration (1 h) exposure of SU5416 was sufficient to block new angiogenic and vasculogenic vessel formation. In contrast, TNP470 required continuous exposure to block SIV formation and had no apparent effect on vasculogenic vessel formation. To ascertain whether blood vessels in the zebrafish embryo respond to angiogenic compounds, we introduced human VEGF into embryos. Injection of VEGF caused an observable increase in SIV formation.

Journal Article↗
PubMed2004

A diffusion model account of normal and impaired readers.

Acquired aphasics and dyslexics with even very profound word reading impairments have been shown to perform relatively well on the lexical decision task, but direct contrasts with unimpaired participant's data is often complicated by extremely long reaction times for patient data. The dissociation between lexical decision and word naming performance shown by these patients is of theoretical importance, and here we present an analysis of processing underlying the lexical decision task. We are able to determine what aspects of performance are affected by acquired aphasics in the lexical decision task. We fit lexical decision data from aphasic patients and from normal readers with a sequential sampling model (the diffusion model) that simultaneously considers reaction time and accuracy. This model provides a powerful means of assessing processes involved in impaired and unimpaired lexical decision. Our results suggest that lexical decision may tap impairments at both a linguistic and a nonlinguistic level. These impairments combine to make patients produce the exaggerated lexical decision reaction times typical of neurolinguistic patients: we demonstrate that patients have compromised decision and nondecision processes but that the quality of the information upon which they base their decisions is not much different from that of unimpaired participants.

Aphasia↗
PubMed2005

Is anoxic depolarisation associated with an ADC threshold? A Markov chain Monte Carlo analysis.

A Bayesian nonlinear hierarchical random coefficients model was used in a reanalysis of a previously published longitudinal study of the extracellular direct current (DC)-potential and apparent diffusion coefficient (ADC) responses to focal ischaemia. The main purpose was to examine the data for evidence of an ADC threshold for anoxic depolarisation. A Markov chain Monte Carlo simulation approach was adopted. The Metropolis algorithm was used to generate three parallel Markov chains and thus obtain a sampled posterior probability distribution for each of the DC-potential and ADC model parameters, together with a number of derived parameters. The latter were used in a subsequent threshold analysis. The analysis provided no evidence indicating a consistent and reproducible ADC threshold for anoxic depolarisation.

Algorithms↗
PubMed2004

Olfactory ensheathing cells promote neurite sprouting of injured axons in vitro by direct cellular contact and secretion of soluble factors.

Olfactory ensheathing cells (OECs) represent an exciting possibility for promoting axonal regeneration within the injured spinal cord. A number of studies have indicated the ability of these cells to promote significant reactive sprouting of injured axons within the injured spinal cord, and in some cases restoration of functional abilities. However, the cellular and/or molecular mechanisms OECs use to achieve this are unclear. To investigate such mechanisms, we report for the first time the ability of OECs to promote post-injury neurite sprouting in an in vitro model of axonal injury. Using this model, we were able to differentiate between the direct and indirect mechanisms underlying the ability of OECs to promote neuronal recovery from injury. We noted that OECs appeared to act as a physical substrate for the growth of post-injury neurite sprouts. We also found that while post-injury sprouting was promoted most when OECs were allowed to directly contact injured neurons, physical separation using tissue culture inserts (1 mm pore size, permeable to diffusible factors but not cells) did not completely block the promoting properties of OECs, suggesting that they also secrete soluble factors which aid post-injury neurite sprouting. Furthermore, this in vitro model allowed direct observation of the cellular interactions between OECs and sprouting neurites using live-cell-imaging techniques. In summary, we found that OECs separately promote neurite sprouting by providing a physical substrate for growth and through the expression of soluble factors. Our findings provide new insight into the ability of OECs to promote axonal regeneration, and also indicate potential targets for manipulation of these cells to enhance their restorative ability.

Animals↗
PubMed2002

Non-Fc-mediated mechanisms are involved in clearance of amyloid-beta in vivo by immunotherapy.

Transgenic (Tg) mouse models overexpressing amyloid precursor protein (APP) develop senile plaques similar to those found in Alzheimer's disease in an age-dependent manner. Recent reports demonstrated that immunotherapy is effective at preventing or removing amyloid-beta deposits in the mouse models. To characterize the mechanisms involved in clearance, we used antibodies of either IgG1 (10d5) or IgG2b (3d6) applied directly to the brains of 18-month-old Tg2576 or 20-month-old PDAPP mice. Both 10d5 and 3d6 led to clearance of 50% of diffuse amyloid deposits in both animal models within 3 d. Fc receptor-mediated clearance has been shown to be important in an ex vivo assay showing antibody-mediated clearance of plaques by microglia. We now show, using in vivo multiphoton microscopy, that FITC-labeled F(ab')2 fragments of 3d6 (which lack the Fc region of the antibody) also led to clearance of 45% of the deposits within 3 d, similar to the results obtained with full-length 3d6 antibody. This result suggests that direct disruption of plaques, in addition to Fc-dependent phagocytosis, is involved in the antibody-mediated clearance of amyloid-beta deposits in vivo. Dense-core deposits that were not cleared were reduced in size by approximately 30% with full-length antibodies and F(ab')2 fragments 3 d after a topical treatment. Together, these results indicate that clearance of amyloid deposits in vivo may involve, in addition to Fc-dependent clearance, a non-Fc-mediated disruption of plaque structure.

Administration, Topical↗
PubMedDate not supplied

Determination of mass and heat transfer parameters during freeze-drying cycles of pharmaceutical products.

The principal aim of this study was to evaluate the water vapour mass transfer resistance of the dried layer and the vial heat transfer coefficient values of a pharmaceutical product during the primary drying period. First, overall vial heat transfer coefficient values, Kv, were determined by a gravimetric method based on pure ice sublimation experiments. Thus, it was possible to set up a map of the total heat flux received by each vial throughout the plate surface of our pilot scale freeze-dryer. Important heterogeneities were observed for the vials placed at the plate edges and for the vials placed at the center of the plate. As well, the same gravimetric method was also used to precisely determine the influence of main lyophilization operating parameters (shelf temperature and gas total pressure) or the vial types and sizes on these overall heat transfer coefficient values. A semi-empirical relationship as a function of total gas pressure was proposed. The transient method by pressure rise analysis (PRA method) after interrupting the water vapour flow between the sublimation chamber and the condenser, previously set up and validated in our laboratory, was then extensively used with an amorphous BSA-based formulation to identify the dried layer mass transfer resistance values, Rp, the ice front temperature, and the total heat transfer coefficient values, Kv, with or without annealing treatment. It was proved that this method gave accurate and coherent data only during the first half of the sublimation period when the totality of the vials of the set was still sublimating. Thus, this rapid method allowed estimation of, on line and in situ, the sublimation front temperature and the characterization of the morphology and structure of the freeze-dried layer, all along the first part of the sublimation period. The estimated sublimation temperatures shown by the PRA model were about 2 degrees C lower than the experimental values obtained using thermocouples inserted inside the vial, in accordance with previous data given by this method for similar freeze-drying conditions. As well, by using this method we could confirm the homogenization of the dried layer porous structure by annealing treatment after the freezing step. Furthermore, frozen matrix structure analysis (mean pore diameter) using optical microscopy and mass transfer modelling of water vapour by molecular diffusion (Knudsen regime) allowed, in some cases, to predict the experimental values of this overall mass transfer resistance directly related to the freeze-dried cake permeability.

Algorithms↗
PubMed2005

Velocity half-sphere model for multiple light scattering in turbid media.

We extend the traditional diffusion theory by distinguishing between the energy radiance in the forward and backward directions at each point in space. This approach leads to a new effective source for the diffusion equation that is nonzero for an anisotropic light source. It differs significantly from the diffusion theory for short source-detector spacings. We derive an analytical solution for the two lowest-order velocity moments of the radiance.

Algorithms↗
PubMed2006

Diffusion with attrition.

This article treats the problem of the sharp front observed when a diffusing substance interacts irreversibly with binding sites within the medium. The model consists of two simultaneous partial differential equations that are nonlinear and cannot be solved in closed form. The parameters are the diffusion coefficient D in the direction under consideration (x), the interaction constant k, the binding-site concentration mu and the boundary concentration of the diffusing ion c(0). Our aim is to develop methods to enable the estimation of these parameters from the experimental data. An analytical solution for the case k --> infinity, as found by others, is given first and then a finite element analysis package is used to obtain numerical solutions for the general case. Graphs are presented to illustrate the effects of the various parameters. Simple graphical procedures are described to compute mu and c (0). The position of the advancing front xi then provides, together with mu, a way to estimate D. A mathematical identity relating D and x and a second one involving D, k and t help to reduce the complexity of the problem. A new, measurable quantity S(t) is defined as [see text] where f is the total concentration (free + bound) of the diffusing ion at time t, and detailed plots are furnished that permit the computation of k directly from S(t), mu and D. The accuracy with which such methods can be expected to determine the various parameters of the model is considered at some length. Finally, in a concluding section, we simulate typical experimental data, examine the validity of our methods, and see how their accuracy is affected by controlled amounts of various kinds of noise.

Biometry↗
PubMed2006

Complete breakdown of the Debye model of rotational relaxation near the isotropic-nematic phase boundary: effects of intermolecular correlations in orientational dynamics.

The Debye-Stokes-Einstein (DSE) model of rotational diffusion predicts that the orientational correlation times tau l vary as [l(l+1)]-1, where l is the rank of the orientational time correlation function (given in terms of the Legendre polynomial of rank l). One often finds significant deviation from this prediction, in either direction. In supercooled molecular liquids where the ratio tau 1/tau 2 falls considerably below 3 (the Debye limit), one usually invokes a jump diffusion model to explain the approach of the ratio tau 1/tau 2 to unity. Here we show in a computer simulation study of a standard model system for thermotropic liquid crystals that this ratio becomes much less than unity as the isotropic-nematic phase boundary is approached from the isotropic side. Simultaneously, the ratio tau 2/eta, eta, being the shear viscosity of the liquid, becomes much larger than the hydrodynamic value near the I-N transition. We also analyze the breakdown of the Debye model of rotational diffusion in ratios of higher order orientational correlation times. We show that the breakdown of the DSE model is due to the growth of orientational pair correlation and provide a mode coupling theory analysis to explain the results.

Journal Article↗
PubMed2005

A new general dynamic model predicting radionuclide concentrations and fluxes in coastal areas from readily accessible driving variables.

This paper presents a general, process-based dynamic model for coastal areas for radionuclides (metals, organics and nutrients) from both single pulse fallout and continuous deposition. The model gives radionuclide concentrations in water (total, dissolved and particulate phases and concentrations in sediments and fish) for entire defined coastal areas. The model gives monthly variations. It accounts for inflow from tributaries, direct fallout to the coastal area, internal fluxes (sedimentation, resuspension, diffusion, burial, mixing and biouptake and retention in fish) and fluxes to and from the sea outside the defined coastal area and/or adjacent coastal areas. The fluxes of water and substances between the sea and the coastal area are differentiated into three categories of coast types: (i) areas where the water exchange is regulated by tidal effects; (ii) open coastal areas where the water exchange is regulated by coastal currents; and (iii) semi-enclosed archipelago coasts. The coastal model gives the fluxes to and from the following four abiotic compartments: surface water, deep water, ET areas (i.e., areas where fine sediment erosion and transport processes dominate the bottom dynamic conditions and resuspension appears) and A-areas (i.e., areas of continuous fine sediment accumulation). Criteria to define the boundaries for the given coastal area towards the sea, and to define whether a coastal area is open or closed are given in operational terms. The model is simple to apply since all driving variables may be readily accessed from maps and standard monitoring programs. The driving variables are: latitude, catchment area, mean annual precipitation, fallout and month of fallout and parameters expressing coastal size and form as determined from, e.g., digitized bathymetric maps using a GIS program. Selected results: the predictions of radionuclide concentrations in water and fish largely depend on two factors, the concentration in the sea outside the given coastal area and/or adjacent coastal areas and the ecological half-life of the radionuclide in the sea. Uncertainties in these factors generally dominate all other uncertainties, e.g., concerning the surface water retention time, the settling velocity of the particulate fraction, the distribution coefficient regulating the fluxes in dissolved and particulate phases, the catchment area influences and the factors regulating biouptake and excretion of the radionuclide in fish. This means that the conditions in the sea are of paramount importance for the conditions in the coastal area, even for relatively enclosed coastal areas. This coastal model may be regarded as a tool for testing working hypotheses on the relative roles of different processes in different coastal areas. Such information is essential for getting realistic expectations of various remedial measures, such as coastal dredging discussed in this work.

Algorithms↗
PubMed2006

Simple data-driven models of intracellular calcium dynamics with predictive power.

Biology is complex. However, it is not clear how much of this complexity must necessarily translate into complicated mathematical models of biological processes. Simple models can be appealing to physicists but are usually deceiving for biologists. Complicated models, on the other hand, depend on too many parameters whose values are frequently unknown. Therefore, complicated models, although in principle more realistic, can lead to erroneous results if they are sensitive to these unknown parameter values. Intracellular calcium signals provide an example of utmost biological importance in which the issue of "simple vs complex" can be explored. In this paper we show that simple models describing the dynamics of intracellular calcium can be directly inferred from experimental data, without no a priori information on unknown parameters. A similar approach can be followed to study other reaction-diffusion systems. In spite of their simplicity, these models can provide quantitative information on some of the processes that shape calcium signals, such as the calcium current that underlies an experimental observation. This shows that simple models of biological systems are not limited to qualitative descriptions.

Animals↗