Cisplatin-induced ototoxicity and pharmacokinetics: Preliminary findings in a dog model

The early effects of clinical dose of cisplatin (100 mg/m(2)) on distort ion-product otoacoustic emissions (DPOAE) thresholds and the relationship between DPOAE threshold shifts and changes in plasma concentrations of filterable and total platinum (Pt) following infusion of cisplatin in a dog model were investigated. The DPOAE thresholds (based on input-output function) were measured 2 days before a single high dose of cisplatin administration, and compared with measurements recorded 2 and 4 days after infusion. The results revealed DPOAE thresholds to be elevated by 4 days after the administration of cisplatin. However, this elevation could not be correlated with plasma concentrations of filterable and total Pt, which showed little variation over the 48-hour postinfusion period between animals. The present study demonstrated that DPOAE thresholds have the potential to be used as an indicator of cisplatin-induced ototoxicity, and cisplatin-induced ototoxicity could not be explained by plasma Pt kinetics in individual animals.

Constraint solving over multi-valued logics - application to digital circuits

Due to usage conditions, hazardous environments or intentional causes, physical and virtual systems are subject to faults in their components, which may affect their overall behaviour. In a ‘black-box’ agent modelled by a set of propositional logic rules, in which just a subset of components is externally visible, such faults may only be recognised by examining some output function of the agent. A (fault-free) model of the agent’s system provides the expected output given some input. If the real output differs from that predicted output, then the system is faulty. However, some faults may only become apparent in the system output when appropriate inputs are given. A number of problems regarding both testing and diagnosis thus arise, such as testing a fault, testing the whole system, finding possible faults and differentiating them to locate the correct one. The corresponding optimisation problems of finding solutions that require minimum resources are also very relevant in industry, as is minimal diagnosis. In this dissertation we use a well established set of benchmark circuits to address such diagnostic related problems and propose and develop models with different logics that we formalise and generalise as much as possible. We also prove that all techniques generalise to agents and to multiple faults. The developed multi-valued logics extend the usual Boolean logic (suitable for faultfree models) by encoding values with some dependency (usually on faults). Such logics thus allow modelling an arbitrary number of diagnostic theories. Each problem is subsequently solved with CLP solvers that we implement and discuss, together with a new efficient search technique that we present. We compare our results with other approaches such as SAT (that require substantial duplication of circuits), showing the effectiveness of constraints over multi-valued logics, and also the adequacy of a general set constraint solver (with special inferences over set functions such as cardinality) on other problems. In addition, for an optimisation problem, we integrate local search with a constructive approach (branch-and-bound) using a variety of logics to improve an existing efficient tool based on SAT and ILP.

Relations and Transductions Realized by Restarting Automata

Gegenstand der vorliegenden Arbeit ist die Analyse verschiedener Formalismen zur Berechnung binärer Wortrelationen. Dabei ist die Grundlage aller hier ausgeführten Betrachtungen das Modell der Restart-Automaten, welches 1995 von Jancar et. al. eingeführt wurde. Zum einen wird das bereits für Restart-Automaten bekannte Konzept der input/output- und proper-Relationen weiterführend untersucht, sowie auf Systeme von zwei parallel arbeitenden und miteinander kommunizierenden Restart-Automaten (PC-Systeme) erweitert. Zum anderen wird eine Variante der Restart-Automaten eingeführt, die sich an klassischen Automatenmodellen zur Berechnung von Relationen orientiert. Mit Hilfe dieser Mechanismen kann gezeigt werden, dass einige Klassen, die durch input/output- und proper-Relationen von Restart Automaten definiert werden, mit den traditionellen Relationsklassen der Rationalen Relationen und der Pushdown-Relationen übereinstimmen. Weiterhin stellt sich heraus, dass das Konzept der parallel kommunizierenden Automaten äußerst mächtig ist, da bereits die Klasse der proper-Relationen von monotonen PC-Systemen alle berechenbaren Relationen umfasst. Der Haupteil der Arbeit beschäftigt sich mit den so genannten Restart-Transducern, welche um eine Ausgabefunktion erweiterte Restart-Automaten sind. Es zeigt sich, dass sich insbesondere dieses Modell mit seinen verschiedenen Erweiterungen und Einschränkungen dazu eignet, eine umfassende Hierarchie von Relationsklassen zu etablieren. In erster Linie seien hier die verschiedenen Typen von monotonen Restart-Transducern erwähnt, mit deren Hilfe viele interessante neue und bekannte Relationsklassen innerhalb der längenbeschränkten Pushdown-Relationen charakterisiert werden. Abschließend wird, im Kontrast zu den vorhergehenden Modellen, das nicht auf Restart-Automaten basierende Konzept des Übersetzens durch Beobachtung ("Transducing by Observing") zur Relationsberechnung eingeführt. Dieser, den Restart-Transducern nicht unähnliche Mechanismus, wird im weitesten Sinne dazu genutzt, einen anderen Blickwinkel auf die von Restart-Transducern definierten Relationen einzunehmen, sowie eine obere Schranke für die Berechnungskraft der Restart-Transducer zu gewinnen.

Previsão do índice bovespa por meio de redes neurais artificiais: uma análise comparada aos métodos tradicionais de séries de tempo

Forecast is the basis for making strategic, tactical and operational business decisions. In financial economics, several techniques have been used to predict the behavior of assets over the past decades.Thus, there are several methods to assist in the task of time series forecasting, however, conventional modeling techniques such as statistical models and those based on theoretical mathematical models have produced unsatisfactory predictions, increasing the number of studies in more advanced methods of prediction. Among these, the Artificial Neural Networks (ANN) are a relatively new and promising method for predicting business that shows a technique that has caused much interest in the financial environment and has been used successfully in a wide variety of financial modeling systems applications, in many cases proving its superiority over the statistical models ARIMA-GARCH. In this context, this study aimed to examine whether the ANNs are a more appropriate method for predicting the behavior of Indices in Capital Markets than the traditional methods of time series analysis. For this purpose we developed an quantitative study, from financial economic indices, and developed two models of RNA-type feedfoward supervised learning, whose structures consisted of 20 data in the input layer, 90 neurons in one hidden layer and one given as the output layer (Ibovespa). These models used backpropagation, an input activation function based on the tangent sigmoid and a linear output function. Since the aim of analyzing the adherence of the Method of Artificial Neural Networks to carry out predictions of the Ibovespa, we chose to perform this analysis by comparing results between this and Time Series Predictive Model GARCH, developing a GARCH model (1.1).Once applied both methods (ANN and GARCH) we conducted the results' analysis by comparing the results of the forecast with the historical data and by studying the forecast errors by the MSE, RMSE, MAE, Standard Deviation, the Theil's U and forecasting encompassing tests. It was found that the models developed by means of ANNs had lower MSE, RMSE and MAE than the GARCH (1,1) model and Theil U test indicated that the three models have smaller errors than those of a naïve forecast. Although the ANN based on returns have lower precision indicator values than those of ANN based on prices, the forecast encompassing test rejected the hypothesis that this model is better than that, indicating that the ANN models have a similar level of accuracy . It was concluded that for the data series studied the ANN models show a more appropriate Ibovespa forecasting than the traditional models of time series, represented by the GARCH model

Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats

Stern JE, Sonner PM, Son SJ, Silva FC, Jackson K, Michelini LC. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats. J Neurophysiol 107: 2912-2921, 2012. First published February 22, 2012; doi:10.1152/jn.00884.2011.-Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na+ spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.

Transfer Functions in Artificial Neural Networks - A Simulation-Based Tutorial

Artificial neural networks are based on computational units that resemble basic information processing properties of biological neurons in an abstract and simplified manner. Generally, these formal neurons model an input-output behaviour as it is also often used to characterize biological neurons. The neuron is treated as a black box; spatial extension and temporal dynamics present in biological neurons are most often neglected. Even though artificial neurons are simplified, they can show a variety of input-output relations, depending on the transfer functions they apply. This unit on transfer functions provides an overview of different transfer functions and offers a simulation that visualizes the input-output behaviour of an artificial neuron depending on the specific combination of transfer functions.

Predicting peroxisomal proteins

PTS1 proteins are peroxisomal matrix proteins that have a well conserved targeting motif at the C-terminal end. However, this motif is present in many non peroxisomal proteins as well, thus predicting peroxisomal proteins involves differentiating fake PTS1 signals from actual ones. In this paper we report on the development of an SVM classifier with a separately trained logistic output function. The model uses an input window containing 12 consecutive residues at the C-terminus and the amino acid composition of the full sequence. The final model gives a Matthews Correlation Coefficient of 0.77, representing an increase of 54% compared with the well-known PeroxiP predictor. We test the model by applying it to several proteomes of eukaryotes for which there is no evidence of a peroxisome, producing a false positive rate of 0.088%.

Efficient training of RBF networks for classification.

Radial Basis Function networks with linear outputs are often used in regression problems because they can be substantially faster to train than Multi-layer Perceptrons. For classification problems, the use of linear outputs is less appropriate as the outputs are not guaranteed to represent probabilities. We show how RBFs with logistic and softmax outputs can be trained efficiently using the Fisher scoring algorithm. This approach can be used with any model which consists of a generalised linear output function applied to a model which is linear in its parameters. We compare this approach with standard non-linear optimisation algorithms on a number of datasets.

Previsão do índice bovespa por meio de redes neurais artificiais: uma análise comparada aos métodos tradicionais de séries de tempo

Forecast is the basis for making strategic, tactical and operational business decisions. In financial economics, several techniques have been used to predict the behavior of assets over the past decades.Thus, there are several methods to assist in the task of time series forecasting, however, conventional modeling techniques such as statistical models and those based on theoretical mathematical models have produced unsatisfactory predictions, increasing the number of studies in more advanced methods of prediction. Among these, the Artificial Neural Networks (ANN) are a relatively new and promising method for predicting business that shows a technique that has caused much interest in the financial environment and has been used successfully in a wide variety of financial modeling systems applications, in many cases proving its superiority over the statistical models ARIMA-GARCH. In this context, this study aimed to examine whether the ANNs are a more appropriate method for predicting the behavior of Indices in Capital Markets than the traditional methods of time series analysis. For this purpose we developed an quantitative study, from financial economic indices, and developed two models of RNA-type feedfoward supervised learning, whose structures consisted of 20 data in the input layer, 90 neurons in one hidden layer and one given as the output layer (Ibovespa). These models used backpropagation, an input activation function based on the tangent sigmoid and a linear output function. Since the aim of analyzing the adherence of the Method of Artificial Neural Networks to carry out predictions of the Ibovespa, we chose to perform this analysis by comparing results between this and Time Series Predictive Model GARCH, developing a GARCH model (1.1).Once applied both methods (ANN and GARCH) we conducted the results' analysis by comparing the results of the forecast with the historical data and by studying the forecast errors by the MSE, RMSE, MAE, Standard Deviation, the Theil's U and forecasting encompassing tests. It was found that the models developed by means of ANNs had lower MSE, RMSE and MAE than the GARCH (1,1) model and Theil U test indicated that the three models have smaller errors than those of a naïve forecast. Although the ANN based on returns have lower precision indicator values than those of ANN based on prices, the forecast encompassing test rejected the hypothesis that this model is better than that, indicating that the ANN models have a similar level of accuracy . It was concluded that for the data series studied the ANN models show a more appropriate Ibovespa forecasting than the traditional models of time series, represented by the GARCH model

Previsão do índice bovespa por meio de redes neurais artificiais: uma análise comparada aos métodos tradicionais de séries de tempo

Forecast is the basis for making strategic, tactical and operational business decisions. In financial economics, several techniques have been used to predict the behavior of assets over the past decades.Thus, there are several methods to assist in the task of time series forecasting, however, conventional modeling techniques such as statistical models and those based on theoretical mathematical models have produced unsatisfactory predictions, increasing the number of studies in more advanced methods of prediction. Among these, the Artificial Neural Networks (ANN) are a relatively new and promising method for predicting business that shows a technique that has caused much interest in the financial environment and has been used successfully in a wide variety of financial modeling systems applications, in many cases proving its superiority over the statistical models ARIMA-GARCH. In this context, this study aimed to examine whether the ANNs are a more appropriate method for predicting the behavior of Indices in Capital Markets than the traditional methods of time series analysis. For this purpose we developed an quantitative study, from financial economic indices, and developed two models of RNA-type feedfoward supervised learning, whose structures consisted of 20 data in the input layer, 90 neurons in one hidden layer and one given as the output layer (Ibovespa). These models used backpropagation, an input activation function based on the tangent sigmoid and a linear output function. Since the aim of analyzing the adherence of the Method of Artificial Neural Networks to carry out predictions of the Ibovespa, we chose to perform this analysis by comparing results between this and Time Series Predictive Model GARCH, developing a GARCH model (1.1).Once applied both methods (ANN and GARCH) we conducted the results' analysis by comparing the results of the forecast with the historical data and by studying the forecast errors by the MSE, RMSE, MAE, Standard Deviation, the Theil's U and forecasting encompassing tests. It was found that the models developed by means of ANNs had lower MSE, RMSE and MAE than the GARCH (1,1) model and Theil U test indicated that the three models have smaller errors than those of a naïve forecast. Although the ANN based on returns have lower precision indicator values than those of ANN based on prices, the forecast encompassing test rejected the hypothesis that this model is better than that, indicating that the ANN models have a similar level of accuracy . It was concluded that for the data series studied the ANN models show a more appropriate Ibovespa forecasting than the traditional models of time series, represented by the GARCH model

Input/output measurements of otoacoustic emissions and differential diagnosis of cochlear function

This study provides detailed information on the ability of healthy ears to generate distortion product otoacoustic emissions (DPOAEs).

Modified radial basis function neural network using output transformation

A modified radial basis function (RBF) neural network and its identification algorithm based on observational data with heterogeneous noise are introduced. The transformed system output of Box-Cox is represented by the RBF neural network. To identify the model from observational data, the singular value decomposition of the full regression matrix consisting of basis functions formed by system input data is initially carried out and a new fast identification method is then developed using Gauss-Newton algorithm to derive the required Box-Cox transformation, based on a maximum likelihood estimator (MLE) for a model base spanned by the largest eigenvectors. Finally, the Box-Cox transformation-based RBF neural network, with good generalisation and sparsity, is identified based on the derived optimal Box-Cox transformation and an orthogonal forward regression algorithm using a pseudo-PRESS statistic to select a sparse RBF model with good generalisation. The proposed algorithm and its efficacy are demonstrated with numerical examples.

Provision of environmental output within a multi-output distance function approach

This paper redefines technical efficiency by incorporating provision of environmental goods as one of the outputs of the farm. The proportion of permanent and rough grassland to total agricultural land area is used as a proxy for the provision of environmental goods. Stochastic frontier analysis was conducted using a Bayesian procedure. The methodology is applied to panel data on 215 dairy farms in England and Wales. Results show that farm efficiency rankings change when provision of environmental outputs by farms is incorporated in the efficiency analysis, which may have important political implications.

Techniques for assessing cardiac output and fetal cardiac function

Fetal echocardiography was initially used to diagnose structural heart disease, but recent interest has focused on functional assessment. Effects of extracardiac conditions on the cardiac function such as volume overload (in the recipient in twin-twin transfusion syndrome), a hyperdynamic circulation (arterio-venous malformation), cardiac compression (diaphragmatic hernia, lung tumours) and increased placental resistance (intrauterine growth restriction and placental insufficiency) can be studied by ultrasound and may guide decisions for intervention or delivery. A variety of functional tests can be used, but there is no single clinical standard. For some specific conditions, however, certain tests have shown diagnostic value.

Measuring Scale Efficiency from the Translog Multi-Input, Multi-Output Distance Function

Ray (1998) developed measures of input- and output-oriented scale efficiency that can be directly computed from an estimated Translog frontier production function. This note extends the earlier results from Ray (1998) to the multiple-output multiple input case.