Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT.

Activation of protein kinase Cepsilon (PKCepsilon), opening of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)), and increased mitochondrial reactive oxygen species (ROS) are key events in the signaling that underlies cardioprotection. We showed previously that mitoK(ATP) is opened by activation of a mitochondrial PKCepsilon, designated PKCepsilon1, that is closely associated with mitoK(ATP). mitoK(ATP) opening then causes an increase in ROS production by complex I of the respiratory chain.

Linear Hopfield networks and constrained optimization.

It is shown that a Hopfield neural network (with linear transfer functions) augmented by an additional feedforward layer can be used to compute the Moore-Penrose generalized inverse of a matrix. The resultant augmented linear Hopfield network can be used to solve an arbitrary set of linear equations or, alternatively, to solve a constrained least squares optimization problem. Applications in signal processing and robotics are considered.

Time delay and causality in biological systems using whitened cross-correlation analysis.

In the study of biological systems, it is often desirable to study the relationship between two simultaneously recorded signals and investigate whether one signal is causing the other. Correlation between signals can be revealed by spectral analysis techniques such as coherence. While coherence reveals the interaction strength between two signals, it does not provide directional information about the direction of causality of the signals, if any.

Cardiovascular signal decomposition and estimation with the extended Kalman smoother.

Cardiovascular signals such as arterial blood pressure (ABP), pulse oximetry (SpO2) and central venous pressure (CVP) contain useful information such as heart rate, respiratory rate, and pulse pressure variation (PPV). We present a statistical state-space model of cardiovascular signals that can be used with the extended Kalman filter or smoother to simultaneously estimate and track many cardiovascular parameters of interest. We demonstrate the algorithm's tracking capabilities with a real ABP signal.

Calculation of the mean pressure with less delay for real-time clinical monitoring.

The mean of cardiovascular pressure signals is an important metric in patient monitoring applications for many types of diseases and injuries. It is typically calculated with a moving average of 3-8 s of the pulsatile signal. This method of calculating the mean introduces a delay of 1.

Mechanical vasoconstriction for a cerebral myogenic autoregulatory model.

This work presents the design of a mechanical vasoconstriction mechanism with application for cerebral autoregulation. The relationship between the applied voltage of a DC motor and the tension within a pressurized vessel wall was utilized for constricting an arteriole segment within an intracranial vascular model. Using current proportional to the string tension, options for closed loop feedback control are considered.

Calibrating an intracranial pressure dynamics model with clinical data - a progress report.

We describe the calibration of a computer model of intracranial pressure (ICP) dynamics to correspond with annotated clinical data taken from a patient being treated for elevated ICP due to a traumatic brain injury. The research protocol employed during treatment includes adjusting the elevation of the head of the bed, adjusting the ventilator settings to induce mild hyperventilation and hypoventilation, and adjusting the height of the cerebrospinal fluid drainage system. The model behavior corresponds to the experimental data quite well in the case of the changing the head of the bed, but less well in the case of changing the ventilator settings.

Detecting tremors in microelectrode recordings without using a spike detector.

Tremor detection in extracellular neuronal recordings has required spike detection because tremors in extracellular neuronal recordings are caused by the fluctuation of action potential's firing rate. This work describes an automatic tremor detection algorithm of extracellular neuronal recordings without using a spike detector. The new algorithm is robust to noise and its performance is not affected by various morphologies of action potentials.

Power spectral density estimation and tracking nonstationary pressure signals based on Kalman filtering.

We describe an algorithm to estimate and track slow changes in power spectral density (PSD) of nonstationary pressure signals. The algorithm is based on a Kalman filter that adaptively generates an estimate of the autoregressive model parameters at each time instant. The algorithm exhibits superior PSD tracking performance in nonstationary pressure signals than classical nonparametric methodologies, and does not assume a piecewise stationary model of the data.

Impulse rejection filter for artifact removal in spectral analysis of biomedical signals.

Biomedical signals are frequently corrupted with artifact that occurs rarely, but is impulsive and large amplitude when it does occur. Because the artifact spans a broad frequency range that overlaps with the signal spectrum, linear filters cannot remove it. Because it is large in amplitude, it dominates characterizations of the signals based on second-order statistics such as correlation and spectral analysis.

A novel statistical model for simulation of arterial and intracranial pressure.

We describe a novel statistical model of pressure signals that incorporates the effects of respiration on arterial (ABP) and intracranial pressure (ICP). This model can be used to synthesize pulsatile ABP and ICP signals with similar time, frequency, and variability characteristics of real pressure signals. These synthetic signals can be used during the development, simulation, or quantitative assessment of biomedical algorithms in a variety of applications.

Variable frequency bioimpedance instrumentation.

The design of instrumentation used to measure the bioimpedance of skin or tissue is presented. An inexpensive, component level approach, appropriate for use by researchers rather that commercial applications, is emphasized. The design and implementation process is thoroughly explained and design tradeoffs are discussed with relation to various applications.

Opening mitoKATP increases superoxide generation from complex I of the electron transport chain.

Opening the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) increases levels of reactive oxygen species (ROS) in cardiomyocytes. This increase in ROS is necessary for cardioprotection against ischemia-reperfusion injury; however, the mechanism of mitoK(ATP)-dependent stimulation of ROS production is unknown. We examined ROS production in suspensions of isolated rat heart and liver mitochondria, using fluorescent probes that are sensitive to hydrogen peroxide.

The direct physiological effects of mitoK(ATP) opening on heart mitochondria.

The mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) has been assigned multiple roles in cell physiology and in cardioprotection. Each of these roles must arise from basic consequences of mitoK(ATP) opening that should be observable at the level of the mitochondrion. MitoK(ATP) opening has been proposed to have three direct effects on mitochondrial physiology: an increase in steady-state matrix volume, respiratory stimulation (uncoupling), and matrix alkalinization.