TauFactor: An open-source application for calculating tortuosity factors from tomographic data

TauFactor is a MatLab application for efficiently calculating the tortuosity factor, as well as volume fractions, surface areas and triple phase boundary densities, from image based microstructural data. The tortuosity factor quantifies the apparent decrease in diffusive transport resulting from convolutions of the flow paths through porous media. TauFactor was originally developed to improve the understanding of electrode microstructures for batteries and fuel cells; however, the tortuosity factor has been of interest to a wide range of disciplines for over a century, including geoscience, biology and optics. It is still common practice to use correlations, such as that developed by Bruggeman, to approximate the tortuosity factor, but in recent years the increasing availability of 3D imaging techniques has spurred interest in calculating this quantity more directly. This tool provides a fast and accurate computational platform applicable to the big datasets (>10^8 voxels) typical of modern tomography, without requiring high computational power

Creating tissue on chip constructs in microtitre plates for drug discovery

We report upon a novel coplanar dielectrophoresis (DEP) based cell patterning system for generating transferrable hepatic cell constructs, resembling a liver-lobule, in culture. The use of paper reinforced gel substrates provided sufficient strength to enable these constructs to be transfered into 96-well plates for long term functional studies, including in the future, drug development studies. Experimental results showed that hepatic cells formed DEP field-induced structures corresponding to an array of lobulemimetic patterns. Hepatic viability was observed over a period of 3 days by the use of a fluorescent cell staining technique, whilst the liver specific functionality of albumin secretion showed a significant enhancement due to the layer patterning of cell lines (HepG2/C3A), compared to 2D patterned cells and un-patterned control. This “build and transfer” concept could, in future, also be adapted for the layer-bylayer construction of organs-on-chip in microtitre formats

Response characteristics in the apex of the gerbil cochlea studied through auditory nerve recordings

In this study, we analyze the processing of low-frequency sounds in the cochlear apex through responses of auditory nerve fibers (ANFs) that innervate the apex. Single tones and irregularly spaced tone complexes were used to evoke ANF responses in Mongolian gerbil. The spike arrival times were analyzed in terms of phase locking, peripheral frequency selectivity, group delays, and the nonlinear effects of sound pressure level (SPL). Phase locking to single tones was similar to that in cat. Vector strength was maximal for stimulus frequencies around 500 Hz, decreased above 1 kHz, and became insignificant above 4 to 5 kHz. We used the responses to tone complexes to determine amplitude and phase curves of ANFs having a characteristic frequency (CF) below 5 kHz. With increasing CF, amplitude curves gradually changed from broadly tuned and asymmetric with a steep low-frequency flank to more sharply tuned and asymmetric with a steep high-frequency flank. Over the same CF range, phase curves gradually changed from a concave-upward shape to a concave-downward shape. Phase curves consisted of two or three approximately straight segments. Group delay was analyzed separately for these segments. Generally, the largest group delay was observed near CF. With increasing SPL, most amplitude curves broadened, sometimes accompanied by a downward shift of best frequency, and group delay changed along the entire range of stimulus frequencies. We observed considerable across-ANF variation in the effects of SPL on both amplitude and phase. Overall, our data suggest that mechanical responses in the apex of the cochlea are considerably nonlinear and that these nonlinearities are of a different character than those known from the base of the cochlea

A Finite Element Model Simulation of Surface EMG Signals Based on Muscle Tissue Dielectric Properties and Electrodes Configuration

A three layer Finite Element Model of skin, fat and skeletal muscle tissue is implemented. The model aims to study the influence of the dielectric properties of the muscle on electromyography signals. The paper focuses on the electrode configuration and its effect on the muscle myoelectric activity detected at the surface. Unlike previous models, the source signal is be generated from recorded intramuscular myoelectric measurements. The finite element model is compared to experimental data and shows a strong correlation in the frequency spectra (r=0.7276) for monopolar recordings but deviates from experimental observations for a bipolar arrangement. Modelling inaccuracies from the input data and experimental noise related to the bipolar modelling are explored

Nonlinear models of development, amplification and compression in the mammalian cochlea

This paper reviews current understanding and presents new results on some of the nonlinear processes that underlie the function of the mammalian cochlea. These processes occur within mechano-sensory hair cells that form part of the organ of Corti. After a general overview of cochlear physiology, mathematical modelling results are presented in three parts. First, the dynamic interplay between ion channels within the sensory inner hair cells is used to explain some new electrophysiological recordings from early development. Next, the state of the art is reviewed in modelling the electro-motility present within the outer hair cells (OHCs), including the current debate concerning the role of cell body motility versus active hair bundle dynamics. A simplified model is introduced that combines both effects in order to explain observed amplification and compression in experiments. Finally, new modelling evidence is presented that structural longitudinal coupling between OHCs may be necessary in order to capture all features of the observed mechanical responses.</jats:p

Structure and mechanics of supporting cells in the guinea pig organ of Corti.

The mechanical properties of the mammalian organ of Corti determine its sensitivity to sound frequency and intensity, and the structure of supporting cells changes progressively with frequency along the cochlea. From the apex (low frequency) to the base (high frequency) of the guinea pig cochlea inner pillar cells decrease in length incrementally from 75-55 µm whilst the number of axial microtubules increases from 1,300-2,100. The respective values for outer pillar cells are 120-65 µm and 1,500-3,000. This correlates with a progressive decrease in the length of the outer hair cells from >100 µm to 20 µm. Deiters'cell bodies vary from 60-50 µm long with relatively little change in microtubule number. Their phalangeal processes reflect the lengths of outer hair cells but their microtubule numbers do not change systematically. Correlations between cell length, microtubule number and cochlear location are poor below 1 kHz. Cell stiffness was estimated from direct mechanical measurements made previously from isolated inner and outer pillar cells. We estimate that between 200 Hz and 20 kHz axial stiffness, bending stiffness and buckling limits increase, respectively,~3, 6 and 4 fold for outer pillar cells, ~2, 3 and 2.5 fold for inner pillar cells and ~7, 20 and 24 fold for the phalangeal processes of Deiters'cells. There was little change in the Deiters'cell bodies for any parameter. Compensating for effective cell length the pillar cells are likely to be considerably stiffer than Deiters'cells with buckling limits 10-40 times greater. These data show a clear relationship between cell mechanics and frequency. However, measurements from single cells alone are insufficient and they must be combined with more accurate details of how the multicellular architecture influences the mechanical properties of the whole organ

Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors

© 2020, The Author(s). We have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner in a model of LPS-induced inflammation. This technology complements existing germline-transgenic models and may be applicable to other rodent disease models

Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

BACKGROUND:In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed.METHODS:A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70Gy (62.4-75Gy).RESULTS:At a median follow-up of 14months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications.CONCLUSIONS:IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]