Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

Computational framework for applying electrical impedance tomography to head imaging

This work introduces a computational framework for applying absolute electrical impedance tomography to head imaging without accurate information on the head shape or the electrode positions. A library of fifty heads is employed to build a principal component model for the typical variations in the shape of the human head, which leads to a relatively accurate parametrization for head shapes with only a few free parameters. The estimation of these shape parameters and the electrode positions is incorporated in a regularized Newton-type output least squares reconstruction algorithm. The presented numerical experiments demonstrate that strong enough variations in the internal conductivity of a human head can be detected by absolute electrical impedance tomography even if the geometric information on the measurement configuration is incomplete to an extent that is to be expected in practice.Comment: 25 pages, 12 figure

The regularized monotonicity method: detecting irregular indefinite inclusions

In inclusion detection in electrical impedance tomography, the support of perturbations (inclusion) from a known background conductivity is typically reconstructed from idealized continuum data modelled by a Neumann-to-Dirichlet map. Only few reconstruction methods apply when detecting indefinite inclusions, where the conductivity distribution has both more and less conductive parts relative to the background conductivity; one such method is the monotonicity method of Harrach, Seo, and Ullrich. We formulate the method for irregular indefinite inclusions, meaning that we make no regularity assumptions on the conductivity perturbations nor on the inclusion boundaries. We show, provided that the perturbations are bounded away from zero, that the outer support of the positive and negative parts of the inclusions can be reconstructed independently. Moreover, we formulate a regularization scheme that applies to a class of approximative measurement models, including the Complete Electrode Model, hence making the method robust against modelling error and noise. In particular, we demonstrate that for a convergent family of approximative models there exists a sequence of regularization parameters such that the outer shape of the inclusions is asymptotically exactly characterized. Finally, a peeling-type reconstruction algorithm is presented and, for the first time in literature, numerical examples of monotonicity reconstructions for indefinite inclusions are presented.Comment: 28 pages, 7 figure

Levenberg-Marquardt algorithm for acousto-electric tomography based on the complete electrode model

The inverse problem in Acousto-Electric tomography concerns the reconstruction of the electric conductivity in a domain from knowledge of the power density function in the interior of the body. This interior power density results from currents prescribed at boundary electrodes (and can be obtained through electro-static boundary measurements together with auxiliary acoustic measurement. In Electrical Impedance Tomography, the complete electrode model is known to be the most accurate model for the forward modelling. In this paper, the reconstruction problem of Acousto-Electric tomography is posed using the (smooth) complete electrode model, and a Levenberg-Marquardt iteration is formulated in appropriate function spaces. This results in a system of partial differential equations to be solved in each iteration. To increase the computational efficiency and stability, a strategy based on both the complete electrode model and the continuum model with Dirichlet boundary condition is proposed. The system of equations is implemented numerically for a two dimensional scenario and the algorithm is tested on two different numerical phantoms, a heart and lung model and a human brain model. Several numerical experiments are carried out confirming the feasibility, accuracy and stability of the methods

Near Real-Time Data Labeling Using a Depth Sensor for EMG Based Prosthetic Arms

Recognizing sEMG (Surface Electromyography) signals belonging to a particular action (e.g., lateral arm raise) automatically is a challenging task as EMG signals themselves have a lot of variation even for the same action due to several factors. To overcome this issue, there should be a proper separation which indicates similar patterns repetitively for a particular action in raw signals. A repetitive pattern is not always matched because the same action can be carried out with different time duration. Thus, a depth sensor (Kinect) was used for pattern identification where three joint angles were recording continuously which is clearly separable for a particular action while recording sEMG signals. To Segment out a repetitive pattern in angle data, MDTW (Moving Dynamic Time Warping) approach is introduced. This technique is allowed to retrieve suspected motion of interest from raw signals. MDTW based on DTW algorithm, but it will be moving through the whole dataset in a pre-defined manner which is capable of picking up almost all the suspected segments inside a given dataset an optimal way. Elevated bicep curl and lateral arm raise movements are taken as motions of interest to show how the proposed technique can be employed to achieve auto identification and labelling. The full implementation is available at https://github.com/GPrathap/OpenBCIPytho

Series reversion for practical electrical impedance tomography with modeling errors

This work extends the results of [Garde and Hyv\"onen, Math. Comp. 91:1925-1953] on series reversion for Calder\'on's problem to the case of realistic electrode measurements, with both the internal admittivity of the investigated body and the contact admittivity at the electrode-object interfaces treated as unknowns. The forward operator, sending the internal and contact admittivities to the linear electrode current-to-potential map, is first proven to be analytic. A reversion of the corresponding Taylor series yields a family of numerical methods of different orders for solving the inverse problem of electrical impedance tomography, with the possibility to employ different parametrizations for the unknown internal and boundary admittivities. The functionality and convergence of the methods is established only if the employed finite-dimensional parametrization of the unknowns allows the Fr\'echet derivative of the forward map to be injective, but we also heuristically extend the methods to more general settings by resorting to regularization motivated by Bayesian inversion. The performance of this regularized approach is tested via three-dimensional numerical examples based on simulated data. The effect of modeling errors is a focal point of the numerical studies.Comment: 24 pages, 3 figure

Evaluating Experimental Design of ERT for Soil Moisture Monitoring in Contour Hedgerow Intercropping Systems

Contour hedgerow intercropping systems have been proposed as an alternative to traditional agricultural practice with a single crop, as they are effective in reducing run-off and soil erosion. However, competition for water and nutrients between crops and associated hedgerows may reduce the overall performance of these systems. To get a more detailed understanding of the competition for water, spatially resolved monitoring of soil water contents in the soil-plant-atmosphere system is necessary. Electrical resistivity tomography (ERT) is potentially a valuable technique to monitor changes in soil moisture in space and time. In this study, the performance of different ERT electrode arrays to detect the soil moisture dynamics in a mono- and an intercropping system was tested. Their performance was analyzed based on a synthetic study using geophysical measures, such as data recovery and resolution, and using spatial statistics of retrieved water content, such as an adjusted coefficient of variation and semivariances. The synthetic ERT measurements detected differences between the cropping systems and retrieved spatial structure of the soil moisture distribution, but the variance and semivariance were underestimated. Sharp water content contrasts between horizons or in the neighborhood of a root water uptake bulb were smoothened. The addition of electrodes deeper in the soil improved the performance, but sometimes only marginally. ERT is therefore a valuable tool for soil moisture monitoring in the field under different cropping systems if an electrode array is used which can resolve the patterns expected to be present in the medium. The use of spatial statistics allowed to not only identify the overall model recovery, but also to quantify the recovery of spatial structures