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Results for “Experimental validation”

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At least 541 records · Page 30Linked to original sources

PubMed2004

Excised porcine skin experimental systems to validate quantitative microdialysis methods for determination of drugs in skin after topical application.

Microdialysis is useful as a method to evaluate the disposition of drugs in the skin to design improved transdermal delivery systems (TDDSs). In this study, quantitative microdialysis methods were validated in excised porcine skin experimental systems in vitro. Flurbiprofen (FP), used as a model drug, showed high affinity for the skin tissues in equilibrium states between the medium and skin. The membrane clearances of FP for permeation through the membrane of a dialysis fiber placed in the skin (CL(m in S)) were lower than that in the medium. The adsorption of components in the skin to the membrane surface of the dialysis fiber and accumulation of FP near the dialysis fiber are the most likely reasons for this. When CL(m in S) was used to predict the extracellular FP concentration in skin (C(T)), the value obtained was lower than that expected from the FP concentration in the medium on the dermis side, which should be equal to C(T) at equilibrium. In the zero net flux (ZNF) method, in which the concentration difference of perfusate (DeltaC) between the inflow and outflow were used to obtain C(T), the predicted C(T) was similar to the expected value. In an in vitro skin permeation experiment, the ZNF method was used for the prediction of C(T) near the dialysis fiber. The predicted C(T) was over 10 times higher than the FP concentration in the medium on the dermis side, suggesting a concentration gradient in the dermis. Although the ZNF method is good for predicting the C(T) in skin, the mass balance has to be considered for the quantitative evaluation of the skin permeation of drugs. In this study, the effect of the mass transfer of FP from the perfusate to the skin on the cumulative amount of FP passing through the skin was relatively low because of the use of suitable solutions as perfusate. The perfusion conditions and schedules should be designed carefully for quantitative evaluations using the ZNF method. These results provide useful information for the in vivo application of quantitative microdialysis to evaluate TDDS.

Administration, Topical↗

PubMed2025

Iterative, multimodal, and scalable single-cell profiling for discovery and characterization of signaling regulators.

Cell signaling plays a critical role in regulating cellular state, yet uncovering regulators of signaling pathways and understanding their molecular consequences remains challenging. Here, we present an iterative experimental and computational framework to identify and characterize regulators of signaling proteins, using the mTOR marker phosphorylated RPS6 (pRPS6) as a case study. We present a customized workflow that uses the 10x Flex assay to jointly profile intracellular protein levels, transcriptomes, and CRISPR perturbations in single cells. We use this to generate a "glossary" dataset of paired protein-RNA measurements across targeted perturbations, which we leverage to train a predictive model of pRPS6 levels based solely on transcriptomic data. Applying this model to a genome-wide Perturb-seq dataset enables in silico screening for pRPS6 and nominates novel regulators of mTOR signaling. Experimental validation confirms these predictions and reveals mechanistic diversity among hits, including changes in signaling output driven by anabolic activity, cellular proliferation and multiple stress pathways. Our work demonstrates how integrated experimental and computational approaches provide a scalable framework for multimodal phenotyping and discovery.

Journal Article↗

PubMed2004

Physiologic-insensitive left ventricular assist predisposes right-sided circulatory failure: a pilot simulation and validation study.

Right-sided circulatory failure (RSCF) is a serious complication in 15-30% of patients receiving a left ventricular assist device (LVAD). It is hypothesized that left ventricular support which lacks physiologic properties predisposes to RSCF. An integral computer simulation and experimental validation protocol was performed. The results suggest that with conventional insensitive left ventricular support right-sided circulatory function is compromised, which may form a substrate for the onset or progress of RSCF. Feedback control of the LVAD could provide a means to counter this problem. A control concept for the LVAD which aims to preserve right-sided circulatory function, while supporting peripheral perfusion, is proposed

Assisted Circulation↗

PubMed2000

Computational and experimental investigation of flow and fluid mixing in the roller bottle bioreactor.

The fully three-dimensional velocity field in a roller bottle bioreactor is simulated for two systems (creeping flow and inertial flow conditions) using a control volume-finite element method, and validated experimentally using particle imaging velocimetry. The velocity fields and flow patterns are described in detail using velocity contour plots and tracer particle pathline computations. Bulk fluid mixing in the roller bottle is then examined using a computational fluid tracer program and flow visualization experiments. It is shown that the velocity fields and flow patterns are substantially different for each of these flow cases. For creeping flow conditions the flow streamlines consist of symmetric, closed three-dimensional loops; and for inertial flow conditions, streamlines consist of asymmetric toroidal surfaces. Fluid tracers remain trapped on these streamlines and are unable to contact other regions of the flow domain. As a result, fluid mixing is greatly hindered, especially in the axial direction. The lack of efficient axial mixing is verified computationally and experimentally. Such mixing limitations, however, are readily overcome by introducing a small-amplitude vertical rocking motion that disrupts both symmetry and recirculation, leading to much faster and complete axial mixing. The frequency of such motion is shown to have a significant effect on mixing rate, which is a critical parameter in the overall performance of roller bottles.

Bioreactors↗

PubMed2000

[Early cellular immune response in experimental labyrinthitis: immunohistochemical study].

Labyrinthitis ossificans is a recently recognized entity with the extending cochlear implant surgery. Up to date there are not so many studies of the cellular response leading the organization of the inflammatory reaction within the cochlea. Immunemediated labyrinthitis is a valid experimental model that allow the knowledge of the cellular infiltration mechanisms within the cochlea. The inner ear communicates with systemic immunity via the circulation by the passage of cells through the spiral modiolar vein (SMV) and its collecting venules in the scala tympani. Inflammatory reaction within the cochlea lead to the formation of fibrotic tissue and bone (osteoneogenesis) inside it and injuring the neurosensory organs of hearing and balance. To test which cells are proliferating early in an inflammatory response, an animal model of Keyhole limpet haemocyanin (KLH) induced labyrinthitis was utilized, showing a granulomatous lesions not previously reported in this experimental model.

Animals↗

PubMed2005

A fully predictive model for one-dimensional light attenuation by Chlamydomonas reinhardtii in a torus photobioreactor.

The light attenuation in a photobioreactor is determined using a fully predictive model. The optical properties were first calculated, using a data bank of the literature, from only the knowledge of pigments content, shape, and size distributions of cultivated cells which are a function of the physiology of the current species. The radiative properties of the biological turbid medium were then deduced using the exact Lorenz-Mie theory. This method is experimentally validated using a large-size integrating sphere photometer. The radiative properties are then used in a rectangular, one-dimensional two-flux model to predict radiant light attenuation in a photobioreactor, considering a quasi-collimated field of irradiance. Combination of this radiative model with the predictive determination of optical properties is finally validated by in situ measurement of attenuation profiles in a torus photobioreactor cultivating the microalgae Chlamydomonas reinhardtii, after a complete and proper characterization of the incident light flux provided by the experimental set-up.

Animals↗

PubMed2000

Conductivity tensor of striped quantum hall phases

We study the transport properties of pinned striped quantum Hall phases. We show that, under quite general assumptions, the macroscopic conductivity tensor satisfies a semicircle law. In particular, this result is valid for both smectic and nematic stripe phases, independent of the presence of topological and orientational defects such as dislocations and grain boundaries. As a special case, our results explain the experimental validity of a product rule for the dissipative part of the resistivity tensor, which was previously derived by MacDonald and Fisher (cond-mat/9907278) for a perfect stripe structure.

Journal Article↗

PubMed2003

Bridging simulations and experiments in microstructure evolution.

We demonstrate the importance of anisotropic interface properties in microstructure evolution by comparing computed evolved microstructures to final experimental microstructures of 5170 grains in 19 thin aluminum foil samples. This is the first time that a direct experimental validation of simulation has been performed at the level of individual grains. We observe that simulated microstructures using curvature-driven grain boundary motion and anisotropic interface properties agree well with experimentally evolved microstructures, whereas agreement is poor when isotropic properties are used.

Journal Article↗

PubMed2006

Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation.

BACKGROUND: Activation of naïve B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only stimulation through the B cell antigen receptor (BCR) induces apoptosis in resting splenic B cells. In order to define the common and unique biological responses to ligand stimulation, we compared the gene expression changes induced in normal primary B cells by a panel of ligands using cDNA microarrays and a statistical approach, CLASSIFI (Cluster Assignment for Biological Inference), which identifies significant co-clustering of genes with similar Gene Ontology annotation. RESULTS: CLASSIFI analysis revealed an overrepresentation of genes involved in ion and vesicle transport, including multiple components of the proton pump, in the BCR-specific gene cluster, suggesting that activation of antigen processing and presentation pathways is a major biological response to antigen receptor stimulation. Proton pump components that were not included in the initial microarray data set were also upregulated in response to BCR stimulation in follow up experiments. MHC Class II expression was found to be maintained specifically in response to BCR stimulation. Furthermore, ligand-specific internalization of the BCR, a first step in B cell antigen processing and presentation, was demonstrated. CONCLUSION: These observations provide experimental validation of the computational approach implemented in CLASSIFI, demonstrating that CLASSIFI-based gene expression cluster analysis is an effective data mining tool to identify biological processes that correlate with the experimental conditional variables. Furthermore, this analysis has identified at least thirty-eight candidate components of the B cell antigen processing and presentation pathway and sets the stage for future studies focused on a better understanding of the components involved in and unique to B cell antigen processing and presentation.

Algorithms↗

PubMed2000

Structural Interpretations of Static Light Scattering Patterns of Fractal Aggregates.

Information on the size and structure of aggregates is critical in predicting the formation kinetics, settling velocities, and reactivity of particle aggregates. For some systems, however, accessing this information may be very difficult. Light scattering measurements are among the most useful techniques for accessing such information. In the case of large primary particles forming aggregates, the common Rayleigh approximation is not valid. Instead, Mie scattering must be used and multiple scattering must be accounted for. Moreover, size polydispersity and structure of aggregates are combined in the scattered intensity measurements. This work presents an experimental validation of a new theoretical approach for extracting information on both aggregate structure and size when multiple scattering cannot be neglected. The chemically controlled aggregation of 0.8-µm latex particles demonstrates the following: (1) Polydispersity effects prevent the interpretation of data to obtain structural information from the Structure factor S(q). (2) The calculated optical contrast decreasing during the aggregation can be correlated with the structural changes in the growing aggregates independently of size polydispersity. We have shown that a strict correlation can be obtained between the fractal dimension D(f) and the scatterers' mean optical contrast calculated at large scattering angles. (3) The changes in the Form factor (F(q)) due to multiple scattering when particles are close together yield a predicted structure that is in agreement with expected fractal dimension values and therefore S(q) can be described in term of both structure and size polydispersity. Copyright 2000 Academic Press.

Journal Article↗

PubMed2001

Depth dependence of the analytical expression for the width of the point spread function (spatial resolution) in time-resolved transillumination.

Simple analytical expressions for the point spread function (PSF) at different depths can save computation time and improve the performance of inverse algorithms for optical imaging. In particular, application of such formulas simplifies quantification of the optical characteristics of tissue abnormalities inside highly scattering media. Earlier it was shown within the random walk theory framework that the PSF for time-resolved transillumination imaging through a highly scattering slab is well represented by a Gaussian. We have experimentally validated a simple formula of the random walk model for the effective width of this Gaussian, as a function of time delay, at different depths of the target. Presented analysis of published experimental data, concerning effective width of the PSF, for a slab of considerably smaller thickness also demonstrates good agreement between the data and predictions of our model. This PSF width determines spatial resolution of the time-resolved imaging and is widely discussed in the literature.

Diagnostic Imaging↗

PubMed2004

Online estimation of wastewater nitrifiable nitrogen, nitrification and denitrification rates, using ORP and DO dynamics.

Biological nitrogen removal is susceptible to disturbances in activated sludge processes. Significant improvement of performances are obtained by controlling the process taking into account wastewater modifications and sludge activity. In this work a specific sensor is developed, based on oxidation-reduction potential (ORP) and dissolved oxygen (DO) measurements performed in a completely mixed reactor which can be the activated sludge basin itself. This reactor is continuously fed by wastewater and sludge issued from the recirculation stream of the process, and submitted to alternating aeration. DO profiles and ORP bending point are linked to nitrification and denitrification in the sensor. Signal dynamics are treated with a physical model for simultaneously estimating nitrifiable nitrogen concentration in wastewater, nitrification rate, and denitrification rate. Results show very good prediction of experimental oxygen profiles and the software sensor allows us to recalculate nitrate and ammonia profiles in the reactor with a good accuracy. The estimation of nitrifiable nitrogen and removal rates has been validated experimentally. The system allows us to follow highly variable influent nitrogen concentration, toxic events, and changes in the COD concentration or quality in wastewater.

Ammonia↗

PubMed2000

Mechanical validation of whole bone composite tibia models.

Composite synthetic models of the human tibia have recently become commercially available as substitutes for cadaveric specimens. Their use is justified by the advantages they offer as a substitute for real tibias. The present investigation concentrated on an extensive experimental validation of the mechanical behaviour of the whole bone composite model, compared to human specimens for different loading conditions. The stiffness of the tibias was measured with a torsional load applied along the long axis, and with a bending load applied both in the latero-medial and in the antero-posterior direction. The bending stiffness of the composite tibias matched well with that of the cadaveric specimens. This was not true for the torsional stiffness. In fact, the composite tibias were much stiffer than the cadaveric specimens, possibly due to the structure of the reinforcement material. The inter-specimen variability for the composite tibias was much lower than that for the cadaveric specimens. Thus, it seems that the composite tibias are suitable to replace cadaveric specimens for certain types of test, whereas they might be unsuitable for others, depending on the loading regimen.

Biomechanical Phenomena↗

PubMed2007

Validation of radiographic simulation codes including x-ray phase effects for millimeter-size objects with micrometer structures.

The mix between x-ray phase and attenuation information needs to be understood for accurate object recovery from radiography and tomography data. We are researching and experimentally validating algorithms that simulate x-ray phase contrast to determine the required physics necessary for quantitative object recovery. The results of a study are described to determine if a multislice (beam-propagation) method is required for simulating x-ray radiographs. We conclude that the multislice method is not required for accurate simulation of greater than or equal to 8 keV x-ray radiographs of millimeter-size objects with micrometer structures.

Algorithms↗

PubMed1994

Dosimetric characteristics, air-kerma strength calibration and verification of Monte Carlo simulation for a new Ytterbium-169 brachytherapy source.

PURPOSE: Ytterbium-169 (169Yb) is a promising new isotope for brachytherapy with a half life of 32 days and an average photon energy of 93 KeV. It has an Ir-192-equivalent dose distribution in water but a much smaller half-value layer in lead (0.2 mm), affording improved radiation protection and customized shielding of dose-limiting anatomic structures. The goals of this study are to: (a) experimentally validate Monte Carlo photon transport dose-rate calculations for this energy range, (b) to develop a secondary air-kerma strength standard for 169Yb, and (c) to present essential treatment planning data including the transverse-axis dose-rate distribution and dose correction factors for a number of local shielding materials. METHODS AND MATERIALS: Several interstitial 169Yb sources (type 6) and an experimental high dose-rate source were made available for this study. Monte-Carlo photon-transport (MCPT) simulations, based upon validated geometric models of source structure, were used to calculate dose rates in water. To verify MCPT predictions, the transverse-axis dose distribution in homogeneous water medium was measured using a silicon-diode detector. For use in designing shielded applicators, heterogeneity correction factors (HCF) arising from small cylindrical heterogeneities of lead, aluminum, titanium, steel and air were measured in a water medium. Finally, to provide a sound experimental basis for comparing experimental and theoretical dose-rate distributions, the air-kerma strength of the sources was measured using a calibrated ion chamber. To eliminate the influence of measurement artifacts on the comparison of theory and measurement, simulated detector readings were compared directly to measured diode readings. The final data are presented in the format endorsed by the Interstitial Collaborative Working Group. RESULTS: The in-air calibration revealed that the air-kerma strength per unit activity (mCi), as quoted by the vendor, varied from 1.30 to 1.57 cGy.cm2/mCi.h depending on seed design. The maximum difference between measured and MCPT-simulated absolute diode readings on the transverse axis was less than 2%, indicating that MCPT accurately predicts dose rate in medium for brachytherapy sources in this energy range. Comparison of measured and simulated HCFs for each of the 16 different cylindrical heterogeneities demonstrated 1-3% agreement. The HCFs vary by as much as 200% with respect to distance and by as much as 48% as a function of disk diameter, showing that HCF is strongly dependent on heterogeneity location and lateral dimensions as well as thickness. The dose-rate constant for water medium was found to be 1.225 cGy/h per kerma unit air-strength and 1.962 cGy/h per unit mCi as measured by the vendor. CONCLUSION: Monte Carlo simulation is an accurate and powerful tool for dosimetric characterization of brachytherapy sources in this energy range. Thin lead foils produce shielding factors comparable to standard shielded applicators for 137Cs. Meaningful theoretical absolute dose calculations in brachytherapy require accurately implemented air-kerma strength standards.

Brachytherapy↗

PubMed1996

Mechanical validation of whole bone composite femur models.

Composite synthetic models of the human femur have recently become commercially available as substitutes for cadaveric specimens. Their quick diffusion was justified by the advantages they offer as a substitute for real femurs. The present investigation concentrated on an extensive experimental validation of the mechanical behaviour of the whole bone composite model, compared to human fresh-frozen and dried-rehydrated specimens for different loading conditions. First, the viscoelastic behaviour of the models was investigated under simulated single leg stance loading, showing that the little time dependent phenomena observed tend to extinguish within a few minutes of the load application. The behaviour under axial loading was then studied by comparing the vertical displacement of the head as well as the axial strains, by application of a parametric descriptive model of the strain distribution. Finally, a four point bending test and a torsional test were performed to characterize the whole bone stiffness of the femur. In all these tests, the composite femurs were shown to fall well within the range for cadaveric specimens, with no significant differences being detected between the synthetic femurs and the two groups of cadaveric femurs. Moreover, the interfemur variability for the composite femurs was 20-200 times lower than that for the cadaveric specimens, thus allowing smaller differences to be characterized as significant using the same simple size, if the composite femurs are employed.

Biomechanical Phenomena↗

PubMed1981

Increased ototoxicity in both young and old mice.

Preweanling, postadolescent, and post-middle-aged CBA/J mice received injections of kanamycin sulfate for two weeks, followed by electrocochleographic (isoelectric auditory nerve-evoked potential thresholds from 2,000 to 64,000 Hz) and histocochleographic (hair cell counts from cochlea whole-mount preparations) analysis. The preweanling mice had structural and functional losses from all portions of the cochlea, while the postadolescent mice had no structural and minimal functional loss. The oldest mice had basal inner and outer hair cell loss and elevated high frequency thresholds. This is an experimental validation of the clinical observation that infants are most susceptible to aminoglycosidic ototoxicity. It also support the suspicion that older persons are also susceptible to ototoxicity and provides the first animal model for experimentally investigating these age-dependent effects.

Aging↗

PubMed2007

Three-dimensional spatial and temporal temperature imaging in gel phantoms using backscattered ultrasound.

Thermal therapies such as radio frequency, heated saline, and high-intensity focused ultrasound ablations are often performed suboptimally due to the inability to monitor the spatial and temporal distribution of delivered heat and the extent of tissue necrosis. Ultrasound-based temperature imaging recently was proposed as a means to measure noninvasively the deposition of heat by tracking the echo arrival time shifts in the ultrasound backscatter caused by changes in speed of sound and tissue thermal expansion. However, the clinical applicability of these techniques has been hampered by the two-dimensional (2-D) nature of traditional ultrasound imaging, and the complexity of the temperature dependence of sound speed for biological tissues. In this paper, we present methodology, results, and validation of a 3-D spatial and temporal ultrasound temperature estimation technique in an alginate-based gel phantom to track the evolution of heat deposition over a treatment volume. The technique was experimentally validated for temperature rises up to approximately 10 degrees C by comparison with measurements from thermocouples that were embedded in the gel. Good agreement (rms difference = 0.12 degrees C, maximum difference = 0.24 degrees C) was observed between the noninvasive ultrasound temperature estimates and thermocouple measurements. Based on the results obtained for the temperature range studied in this paper, the technique demonstrates potential for applicability in image guidance of thermal therapy for determining the location of the therapeutic focal spot and assessing the extent of the heated region at subablative intensities.

Algorithms↗