Francisco Sepulveda

Separation of drug transport and chloride channel functions of the human multidrug resistance P-glycoprotein

The human multidrug resistance P-glycoprotein is an active transporter that pumps cytotoxic drugs out of cells. Expression of P-glycoprotein is also associated with a volume-activated chloride channel. Here we address the relationship between these two functions. Drug transport requires ATP hydrolysis while, in contrast, ATP binding is sufficient to enable activation of the chloride channel. The chloride channel and drug transport activities of P-glycoprotein appear to reflect two distinct functional states of the protein that can be interconverted by changes in tonicity. Transportable drugs prevent channel activation but have no effect on channel activity once it has been preactivated by hypotonicity. The transport and channel functions of P-glycoprotein have been separated by directed mutations in the nucleotide-binding domains of the protein. These data provide further evidence that P-glycoprotein is bifunctional with both transport and channel activities. Implications for the design of chemotherapeutic drugs and for the function of the related cystic fibrosis gene product, CFTR, are discussed.

Classifying mental tasks based on features of higher-order statistics from EEG signals in brain-computer interface

In order to characterize the non-Gaussian information contained within the EEG signals, a new feature extraction method based on bispectrum is proposed and applied to the classification of right and left motor imagery for developing EEG-based brain-computer interface systems. The experimental results on the Graz BCI data set have shown that based on the proposed features, a LDA classifier, SVM classifier and NN classifier outperform the winner of the BCI 2003 competition on the same data set in terms of either the mutual information, the competition criterion, or misclassification rate.

A NEURAL NETWORK REPRESENTATION OF ELECTROMYOGRAPHY AND JOINT DYNAMICS IN HUMAN GAIT

Optimization theory and other mathematical algorithms have traditionally been used to model the relationship between muscle activity and lower-limb dynamics during human gait. We introduce here an alternative approach, based on artificial neural networks with the back-propagation algorithm, to map two different transformations: (1) EMG-->joint angles; and (2) EMG-->joint moments. Normal data for 16 muscles and three joint moments and angles (hip, knee, and ankle) were adapted from the literature [Winter (1987), The Biomechanics and Motor Control of Human Gait]. Both networks were successfully trained to map the input vector onto the output vector. The models were tested by feeding in an input vector where all 16 muscles were slightly different (20%) from the training data, and the predicted output vectors suggested that the models were valid. The trained networks were then used to perform two separate simulations: 30% reduction in soleus activity; and removal of rectus femoris. Net 2, in which electromyography was mapped onto joint moments, provided the most reasonable results, suggesting that neural networks can provide a successful platform for both biomechanical modeling and simulation. We believe that this paper has demonstrated the potential of artificial neural networks, and that further efforts should be directed towards the development of larger training sets based on normal and pathological data.

Visual modifications on the P300 speller BCI paradigm

The best known P300 speller brain-computer interface (BCI) paradigm is the Farwell and Donchin paradigm. In this paper, various changes to the visual aspects of this protocol are explored as well as their effects on classification. Changes to the dimensions of the symbols, the distance between the symbols and the colours used were tested. The purpose of the present work was not to achieve the highest possible accuracy results, but to ascertain whether these simple modifications to the visual protocol will provide classification differences between them and what these differences will be. Eight subjects were used, with each subject carrying out a total of six different experiments. In each experiment, the user spelt a total of 39 characters. Two types of classifiers were trained and tested to determine whether the results were classifier dependant. These were a support vector machine (SVM) with a radial basis function (RBF) kernel and Fishers linear discriminant (FLD). The single-trial classification results and multiple-trial classification results were recorded and compared. Although no visual protocol was the best for all subjects, the best performances, across both classifiers, were obtained with the white background (WB) visual protocol. The worst performance was obtained with the small symbol size (SSS) visual protocol.

Volume-activated chloride channels in HeLa cells are blocked by verapamil and dideoxyforskolin

The possible role of Cl− currents in regulatory volume decrease processes has been explored in HeLa cells using the whole-cell recording mode of the patch-clamp technique. Cells showed very small currents in voltage-clamp experiments performed with Cl−-rich, permeant-cation-free (N-methyl-d-glucamine replacement) intracellular and bathing solutions. Exposure of the cells to hypotonic solutions visibly swelled the cells and activated, reversibly, an outward rectifying Cl− current, which decayed at the most depolarised voltages used. Replacement of extracellular Cl− by a series of halide anions, SCN− and gluconate was consistent with an anion selectivity sequence: SCN−>I−>Br−>Cl− >F−>gluconate. The volume-regulated Cl− current was effectively inhibited by 100 μM 5-nitro-2-(3-phenylpropylamino)-benzoic acid and by 100 μM 4,4′-diisothiocyanotostilbene-2,2-disulphonic acid, substances known to block Cl− channels in a variety of cells. Chloride current activation by hypotonicity was dependent on the presence of ATP in the intracellular solution and this requirement could be replaced by the non-hydrolysable analogue ATP[γS] and Mg2+-free ATP. The data suggest that the channels responsible for the current described are involved in the regulatory volume decrease in HeLa cells. The characteristics of this Cl− current are similar to those of the current associated with expression of multidrug resistance P-glycoprotein. Furthermore, the currents in HeLa cells were inhibited rapidly and reversibly by verapamil and 1,9-dideoxyforskolin, which are known to inhibit P-glycoprotein function.

A user-independent real-time emotion recognition system for software agents in domestic environments

The mystery surrounding emotions, how they work and how they affect our lives has not yet been unravelled. Scientists still debate the real nature of emotions, whether they are evolutionary, physiological or cognitive are just a few of the different approaches used to explain affective states. Regardless of the various emotional paradigms, neurologists have made progress in demonstrating that emotion is as, or more, important than reason in the process of making decisions and deciding actions. The significance of these findings should not be overlooked in a world that is increasingly reliant on computers to accommodate to user needs. In this paper, a novel approach for recognizing and classifying positive and negative emotional changes in real time using physiological signals is presented. Based on sequential analysis and autoassociative networks, the emotion detection system outlined here is potentially capable of operating on any individual regardless of their physical state and emotional intensity without requiring an arduous adaptation or pre-analysis phase. Results from applying this methodology on real-time data collected from a single subject demonstrated a recognition level of 71.4% which is comparable to the best results achieved by others through off-line analysis. It is suggested that the detection mechanism outlined in this paper has all the characteristics needed to perform emotion recognition in pervasive computing.

P300-Based BCI Mouse With Genetically-Optimized Analogue Control

In this paper we propose a brain-computer interface (BCI) mouse based on P300 waves in electroencephalogram (EEG) signals. The system is analogue in that at no point a binary decision is made as to whether or not a P300 was actually produced in response to the stimuli. Instead, the 2D motion of the pointer on the screen, using a novel BCI paradigm, is controlled by directly combining the amplitudes of the output produced by a filter in the presence of different stimuli. This filter and the features to be combined within it are optimised by an evolutionary algorithm.

Facilitated transport of amino acids through the blood-brain barrier of the dog studied in a single capillary circulation

Summary (1) The single circulation multiple tracer diffusion technique was used to measure in vivo the fractional loss of a labeled amino acid from blood into brain. A mixture of 22 Na (intravascular reference) and a labeled amino acids was injected into the carotid artery. (2) The fractional extraction of the following l -isomers was measured. (a) Neutral: [ 14 C]glycine, [ 14 C]alanine, [ 14 C]GABA, [ 14 C]valine, [ 14 C]glutamine, [ 3 H]leucine, [ 3 H]tyrosine, [ 3 H]phenylalanine and [ 3 H]histidine. (b) Basic: [ 3 H]lysine and [ 14 C]arginine. (c) Acidic: [ 14 C]aspartic acid and [ 3 H]glutamic acid. (3) Only neutral amino acids showed significant fractional losses: valine (0.17 ± 0.05), leucine (0.33 ± 0.05), tyrosine (0.47 ± 0.04), phenylalanine (0.39 ± 0.07) and hisitidine (0.26 ± 0.06). These values were reduced when the specific activity in the injectate was lowered by adding ‘cold’ amino acid. Cross-inhibition was also demonstrated. Tryptophan inhibited leucine transport, whereas d -glucose did not affect it. Serine, which is not significantly lost from blood, did not inhibited phenylalanine transport. (4) It is concluded that, in dog, brain capillary possesses a common mediated transport system for the long-chain neutral amino acids which is distinct from the d -glucose system. (5) The in vivo , non-destructive method used here can be applied to amino acid transport studies in humans.

Does short-term exposure to mobile phone base station signals increase symptoms in individuals who report sensitivity to electromagnetic fields? A double-blind randomized provocation study

Background Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. Objectives This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Methods Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. Results During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Conclusions Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself.

A Review of Non-Invasive Techniques to Detect and Predict Localised Muscle Fatigue

Muscle fatigue is an established area of research and various types of muscle fatigue have been investigated in order to fully understand the condition. This paper gives an overview of the various non-invasive techniques available for use in automated fatigue detection, such as mechanomyography, electromyography, near-infrared spectroscopy and ultrasound for both isometric and non-isometric contractions. Various signal analysis methods are compared by illustrating their applicability in real-time settings. This paper will be of interest to researchers who wish to select the most appropriate methodology for research on muscle fatigue detection or prediction, or for the development of devices that can be used in, e.g., sports scenarios to improve performance or prevent injury. To date, research on localised muscle fatigue focuses mainly on the clinical side. There is very little research carried out on the implementation of detecting/predicting fatigue using an autonomous system, although recent research on automating the process of localised muscle fatigue detection/prediction shows promising results.