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Electric field mediated drug and gene delivery is a novel method that uses pulsed electric fields to improve permeability of cell membranes and therefore desired agent uptake by tissues. In this paper, we describe the modeling and experimental proof of concept of a method to direct electric fields to subsequently focus drug or gene uptake at a desired site. The in vitro experimental results presented...
Electrocorticogram recordings for neuroprosthetics provide an intermediate level of abstraction between EEG and microwire single neuron recordings. For adaptive filtering methodologies used in neuroprosthetics, extraction of spatio-control parameters remains a difficulty. Since amplitude modulation in extracellular recordings plays a key role in both neuronal activation and rate coding, seeking spatial...
Deep brain stimulation (DBS) has been shown to generate suppression of abnormal neural activity in patients with Parkinson's disease and epilepsy. High frequency stimulation is applied to the brain through depth electrodes in the range of 50 to 200 Hz. Yet the mechanisms underlying the suppression effect have not yet been elucidated. In order to study directly the effect of HFS in the brain, sinusoidal...
Small (down to 1 mV/mm) electric fields will polarize neurons by only a small amount; for this reason small electric fields have previously been considered to have no physiologically relevant effects. However, here we propose a novel mechanism by which the non-linear properties of single neurons 'amplify' very small electric fields. Specifically, an amplified change in timing of action potential firing...
Nano red elemental selenium (Nano-Se), was demonstrated to be useful in medical and scientific researches. Here, we investigated the effects of Nano-Se on sodium currents on rat dorsal root ganglion neurons (DRG), using the whole-cell patch clamp method. Nano-Se reversibly decrease the INa(TTX-S) in a concentration-dependent, time-dependent and open-channel block manners without affecting INa(TTX-R)...
Our aim is to assess and quantify the exact effects of the induction of long term potentiation (LTP) on tonic inhibition and facilitation in a neural circuit within the hippocampal formation of neonatal rats. The neural circuit of interest in this paper is the perforant pathway-dentate gyrus synapse which serves as the first leg of the hippocampal trisynaptic circuit. A quantitative measure of the...
The uterus is a physiological system consisting of a large number of interacting smooth muscle cells. The uterine excitability changes remarkably with time, generally quiescent during pregnancy, the uterus exhibits forceful synchronized contractions at term leading to fetus expulsion. These changes characterize thus a dynamical system susceptible of being studied through formal mathematical tools...
We propose a hierarchical parameter optimization technique which further enhances our original technique for an accurate biological cell simulation. Our original technique generates a k-d tree and uses the coefficient of multiple determination (R2) for tree-branching, however it requires a huge computation time since it processes the response surface at every leaf node of the k-d tree, including those...
We present a refined method and design for building parylene neurocages for in vitro studies of live neural networks. Parylene neurocages are biocompatible and very robust, making them ideally suited for studying the synaptic connections between individual neurons to gain insight into learning and memory. The neurocage fabrication process incorporates electrodes into the neurocages to allow for stimulation...
Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics...
Studies examining traumatic brain injury have suggested a 'window of opportunity' exists for therapeutic agents to mitigate edema and cellular toxicity effectively. However, successful therapy also relies on identifying the extent of blood-brain barrier disruption, which is associated with excessive extra-cellular concentrations of ions, excitatory amino acids, and serum proteins. The following study...
Accurate cardiac tissue-based modeling using the bidomain equations requires the incorporation of fine-scale structures observed at the 50-100 micron level. By including such features we can more easily observe how defibrillation shocks lead to total depolarization of the heart. Several modeling studies that have investigated the effect of fine scale structures on defibrillation success have been...
Deep brain stimulation (DBS) has been shown to generate suppression of abnormal neural activity in patients with Parkinson's disease and epilepsy. High frequency stimulation is applied to the brain through depth electrodes in the range of 50 to 200 Hz. Yet the mechanisms underlying the suppression effect have not yet been elucidated. In order to study directly the effect of HFS in the brain, sinusoidal...
A bidomain reaction-diffusion model of the human heart was developed and potentials resulting from normal depolarization and repolarization were compared with results from a compatible monodomain model. Comparisons were made for an empty isolated heart and for a heart with fluid-filled ventricles. Both sinus rhythm and ectopic activation were simulated. The model took 2 days on 32 processors to simulate...
Studies examining traumatic brain injury have suggested a 'window of opportunity' exists for therapeutic agents to mitigate edema and cellular toxicity effectively. However, successful therapy also relies on identifying the extent of blood-brain barrier disruption, which is associated with excessive extra-cellular concentrations of ions, excitatory amino acids, and serum proteins. The following study...
Several important non-cardiac drugs have been removed from the market after revealing harmful effect that was not identified during prior safety-assessment studies. We developed a new technique for the measurements of repolarization abnormalities from surface ECGs; this method improves sensitivity and specificity of the current technique used to identify the presence of abnormal ion current kinetics...
We propose a hierarchical parameter optimization technique which further enhances our original technique for an accurate biological cell simulation. Our original technique generates a k-d tree and uses the coefficient of multiple determination (R2) for tree-branching, however it requires a huge computation time since it processes the response surface at every leaf node of the k-d tree, including those...
Dentate granule cells receive inputs from the entorhinal cortex as the "perforant path". There are two components of the perforant path: the lateral component (LPP) and the medial component (MPP). LPP and MPP convey different sensory modality information. It remains elusive as to how signals from different inputs interact and integrate at the granule cell level. We attempted to address this...
Electric field mediated drug and gene delivery is a novel method that uses pulsed electric fields to improve permeability of cell membranes and therefore desired agent uptake by tissues. In this paper, we describe the modeling and experimental proof of concept of a method to direct electric fields to subsequently focus drug or gene uptake at a desired site. The in vitro experimental results presented...
We introduce cycle-linear hybrid automata (CLHA) and show how they can be used to efficiently model dynamical systems that exhibit nonlinear, pseudo-periodic behavior. CLHA are based on the observation that such systems cycle through a fixed set of operating modes, although the dynamics and duration of each cycle may depend on certain computational aspects of past cycles. CLHA are constructed around...
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