Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status.

Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.

Mock Circulatory Loop Compliance Chamber Employing a Novel Real-Time Control Process.

The use of compliance chambers in mock circulatory loop construction is the predominant means of simulating arterial compliance. Utilizing mock circulatory loops as bench test methods for cardiac assist technologies necessitates that they must be capable of reproducing the circulatory conditions that would exist physiologically. Of particular interest is the ability to determine instantaneous compliance of the system, and the ability to change the compliance in real-time. This capability enables continuous battery testing of conditions without stopping the flow to change the compliance chamber settings, and the simulation of dynamic changes in arterial compliance. The method tested involves the use of a compliance chamber utilizing a circular natural latex rubber membrane separating the fluid and air portions of the device. Change in system compliance is affected by the airspace pressure, which creates more reaction force at the membrane to the fluid pressure. A pressure sensor in the fluid portion of the chamber and a displacement sensor monitoring membrane center deflection allow for real-time inputs to the control algorithm. A predefined numerical model correlates the displacement sensor data to the volume displacement of the membrane. The control algorithm involves a tuned π loop maintaining the volume distention of the membrane via regulation of the air space pressure. The proportional integral (PI) controller tuning was achieved by creating a computational model of the compliance chamber using Simulink™ Simscape® toolboxes. These toolboxes were used to construct a model of the hydraulic, mechanical, and pneumatic elements in the physical design. Parameter Estimation™ tools and Design Optimization™ methods were employed to determine unknown physical parameters in the system, and tune the process controller used to maintain the compliance setting. It was found that the resulting control architecture was capable of maintaining compliance along a pressure-volume curve and allowed for changes to the compliance set point curve without stopping the pulsatile flow.

Investigation of an HMM/ANN hybrid structure in pattern recognition application using cepstral analysis of dysarthric (distorted) speech signals.

Computer speech recognition of individuals with dysarthria, such as cerebral palsy patients requires a robust technique that can handle conditions of very high variability and limited training data. In this study, application of a 10 state ergodic hidden Markov model (HMM)/artificial neural network (ANN) hybrid structure for a dysarthric speech (isolated word) recognition system, intended to act as an assistive tool, was investigated. A small size vocabulary spoken by three cerebral palsy subjects was chosen. The effect of such a structure on the recognition rate of the system was investigated by comparing it with an ergodic hidden Markov model as a control tool. This was done in order to determine if this modified technique contributed to enhanced recognition of dysarthric speech. The speech was sampled at 11 kHz. Mel frequency cepstral coefficients were extracted from them using 15 ms frames and served as training input to the hybrid model setup. The subsequent results demonstrated that the hybrid model structure was quite robust in its ability to handle the large variability and non-conformity of dysarthric speech. The level of variability in input dysarthric speech patterns sometimes limits the reliability of the system. However, its application as a rehabilitation/control tool to assist dysarthric motor impaired individuals holds sufficient promise.

Effect of high-frequency spectral components in computer recognition of dysarthric speech based on a Mel-cepstral stochastic model.

Computer speech recognition of individuals with dysarthria, such as cerebral palsy patients, requires a robust technique that can handle conditions of very high variability and limited training data. In this study, a hidden Markov model (HMM) was constructed and conditions investigated that would provide improved performance for a dysarthric speech (isolated word) recognition system intended to act as an assistive/control tool. In particular, we investigated the effect of high-frequency spectral components on the recognition rate of the system to determine if they contributed useful additional information to the system. A small-size vocabulary spoken by three cerebral palsy subjects was chosen. Mel-frequency cepstral coefficients extracted with the use of 15 ms frames served as training input to an ergodic HMM setup. Subsequent results demonstrated that no significant useful information was available to the system for enhancing its ability to discriminate dysarthric speech above 5.5 kHz in the current set of dysarthric data. The level of variability in input dysarthric speech patterns limits the reliability of the system. However, its application as a rehabilitation/control tool to assist dysarthric motor-impaired individuals such as cerebral palsy subjects holds sufficient promise.

Experiments with fast Fourier transform, linear predictive and cepstral coefficients in dysarthric speech recognition algorithms using hidden Markov Model.

In this study, a hidden Markov Model was constructed and conditions were investigated that would provide improved performance for a dysarthric speech (isolated word) recognition system. The speaker dependant system was intended to act as an assistive/control tool. A small size vocabulary spoken by three cerebral palsy subjects was chosen. Fast Fourier transform, linear predictive, and Mel frequency cepstral coefficients extracted from data provided training input to several whole-word hidden Markov model configurations. The effect of model structure, number of states, and frame rates were also investigated. It was noted that a 10-state ergodic model using 15 msec frames was better than other configurations. Furthermore, it was found that a Mel cepstrum based model outperformed a fast Fourier transform and linear prediction based model. The system offers effective and robust application as a rehabilitation and/or control tool to assist dysarthric motor impaired individuals.

Flow through an outlet cannula of a rotary ventricular assist device.

Rotary ventricular assist devices (VADs) are primarily used during surgery and short-term postoperative assistance. There are issues involving the use of rotary VADs including the behavior of flow emanating from the assist device which might induce flow irregularities that could potentially lead to stroke or cerebrovascular accident. An in vitro flow visualization study using particle image velocimetry was conducted to evaluate flow fields at the bend of outlet cannulae with angles ranging from 30 degrees to 75 degrees. A multiple disk centrifugal blood pump produced steady, laminar flow fields at the outlet. Flow fields at the bend of each cannula demonstrated the development of a boundary layer along the inner wall and shift of fluid momentum to the outer wall. Stagnant zones along the inner wall were prevalent for each cannula and increased in severity with increasing angle. The outlet flow fields of rotary VADs have the potential to produce thrombus, feasibly leading to thromboembolisms should the bend angle of the outlet cannula be acute enough. Therefore, the placement of the outlet cannula or conduit should be taken into consideration during implantation.