New approaches to open problems in gene expression microarray data

In the past decade, the advent of efficient genome sequencing tools and high-throughput experimental biotechnology has lead to enormous progress in the life science. Among the most important innovations is the microarray tecnology. It allows to quantify the expression for thousands of genes simultaneously by measurin the hybridization from a tissue of interest to probes on a small glass or plastic slide. The characteristics of these data include a fair amount of random noise, a predictor dimension in the thousand, and a sample noise in the dozens. One of the most exciting areas to which microarray technology has been applied is the challenge of deciphering complex disease such as cancer. In these studies, samples are taken from two or more groups of individuals with heterogeneous phenotypes, pathologies, or clinical outcomes. these samples are hybridized to microarrays in an effort to find a small number of genes which are strongly correlated with the group of individuals. Eventhough today methods to analyse the data are welle developed and close to reach a standard organization (through the effort of preposed International project like Microarray Gene Expression Data -MGED- Society [1]) it is not unfrequant to stumble in a clinician's question that do not have a compelling statistical method that could permit to answer it.The contribution of this dissertation in deciphering disease regards the development of new approaches aiming at handle open problems posed by clinicians in handle specific experimental designs. In Chapter 1 starting from a biological necessary introduction, we revise the microarray tecnologies and all the important steps that involve an experiment from the production of the array, to the quality controls ending with preprocessing steps that will be used into the data analysis in the rest of the dissertation. While in Chapter 2 a critical review of standard analysis methods are provided stressing most of problems that In Chapter 3 is introduced a method to adress the issue of unbalanced design of miacroarray experiments. In microarray experiments, experimental design is a crucial starting-point for obtaining reasonable results. In a two-class problem, an equal or similar number of samples it should be collected between the two classes. However in some cases, e.g. rare pathologies, the approach to be taken is less evident. We propose to address this issue by applying a modified version of SAM [2]. MultiSAM consists in a reiterated application of a SAM analysis, comparing the less populated class (LPC) with 1,000 random samplings of the same size from the more populated class (MPC) A list of the differentially expressed genes is generated for each SAM application. After 1,000 reiterations, each single probe given a "score" ranging from 0 to 1,000 based on its recurrence in the 1,000 lists as differentially expressed. The performance of MultiSAM was compared to the performance of SAM and LIMMA [3] over two simulated data sets via beta and exponential distribution. The results of all three algorithms over low- noise data sets seems acceptable However, on a real unbalanced two-channel data set reagardin Chronic Lymphocitic Leukemia, LIMMA finds no significant probe, SAM finds 23 significantly changed probes but cannot separate the two classes, while MultiSAM finds 122 probes with score >300 and separates the data into two clusters by hierarchical clustering. We also report extra-assay validation in terms of differentially expressed genes Although standard algorithms perform well over low-noise simulated data sets, multi-SAM seems to be the only one able to reveal subtle differences in gene expression profiles on real unbalanced data. In Chapter 4 a method to adress similarities evaluation in a three-class prblem by means of Relevance Vector Machine [4] is described. In fact, looking at microarray data in a prognostic and diagnostic clinical framework, not only differences could have a crucial role. In some cases similarities can give useful and, sometimes even more, important information. The goal, given three classes, could be to establish, with a certain level of confidence, if the third one is similar to the first or the second one. In this work we show that Relevance Vector Machine (RVM) [2] could be a possible solutions to the limitation of standard supervised classification. In fact, RVM offers many advantages compared, for example, with his well-known precursor (Support Vector Machine - SVM [3]). Among these advantages, the estimate of posterior probability of class membership represents a key feature to address the similarity issue. This is a highly important, but often overlooked, option of any practical pattern recognition system. We focused on Tumor-Grade-three-class problem, so we have 67 samples of grade I (G1), 54 samples of grade 3 (G3) and 100 samples of grade 2 (G2). The goal is to find a model able to separate G1 from G3, then evaluate the third class G2 as test-set to obtain the probability for samples of G2 to be member of class G1 or class G3. The analysis showed that breast cancer samples of grade II have a molecular profile more similar to breast cancer samples of grade I. Looking at the literature this result have been guessed, but no measure of significance was gived before.

Vibrations, Posture, and the Stabilization of Gaze: An Experimental Study on Impedance Control

Vibrations, Posture, and the Stabilization of Gaze: An Experimental Study on Impedance Control R. KREDEL, A. GRIMM & E.-J. HOSSNER University of Bern, Switzerland Introduction Franklin and Wolpert (2011) identify impedance control, i.e., the competence to resist changes in position, velocity or acceleration caused by environmental disturbances, as one of five computational mechanisms which allow for skilled and fluent sen-sorimotor behavior. Accordingly, impedance control is of particular interest in situa-tions in which the motor task exhibits unpredictable components as it is the case in downhill biking or downhill skiing. In an experimental study, the question is asked whether impedance control, beyond its benefits for motor control, also helps to stabi-lize gaze what, in turn, may be essential for maintaining other control mechanisms (e.g., the internal modeling of future states) in an optimal range. Method In a 3x2x4 within-subject ANOVA design, 72 participants conducted three tests on visual acuity and contrast (Landolt / Grating and Vernier) in two different postures (standing vs. squat) on a platform vibrating at four different frequencies (ZEPTOR; 0 Hz, 4 Hz, 8 Hz, 12 Hz; no random noise; constant amplitude) in a counterbalanced or-der with 1-minute breaks in-between. In addition, perceived exertion (Borg) was rated by participants after each condition. Results For Landolt and Grating, significant main effects for posture and frequency are re-vealed, representing lower acuity/contrast thresholds for standing and for higher fre-quencies in general, as well as a significant interaction (p < .05), standing for in-creasing posture differences with increasing frequencies. Overall, performance could be maintained at the 0 Hz/standing level up to a frequency of 8 Hz, if bending of the knees was allowed. The fact that this result is not only due to exertion is proved by the Borg ratings showing significant main effects only, i.e., higher exertion scores for standing and for higher frequencies, but no significant interaction (p > .40). The same pattern, although not significant, is revealed for the Vernier test. Discussion Apparently, postures improving impedance control not only turn out to help to resist disturbances but also assist in stabilizing gaze in spite of these perturbations. Con-sequently, studying the interaction of these control mechanisms in complex unpre-dictable environments seems to be a fruitful field of research for the future. References Franklin, D. W., & Wolpert, D. M. (2011). Computational mechanisms of sensorimotor control. Neuron, 72, 425-442.

Implementación de instrumentación virtual con LaBVIEW

El objetivo del PFC es el diseño e implementación de una aplicación que funcione como osciloscopio, analizador de espectro y generador de funciones virtual, todo dentro de la misma aplicacion. Mediante una tarjeta de adquisición de datos tomaremos muestras de señales del mundo real (sistema analógico) para generar datos que puedan ser manipulados por un ordenador (sistema digital). Con esta misma tarjeta también se podrán generar señales básicas, tales como señales senoidales, cuadradas.... y además se ha añadido la funcionalidad de generar señales moduladas en frecuencia, señales tipo Chirp (usadas comúnmente tanto en aplicaciones sonar y radar, como en transmisión óptica) o PRN (ruido pseudo-aleatorio que consta de una secuencia determinista de pulsos que se repite cada periodo, usada comúnmente en receptores GPS), como también señales ampliamente conocidas como el ruido blanco Gaussiano o el ruido blanco uniforme. La aplicación mostrará con detalle las señales adquiridas y analizará de diversas maneras esas señales. Posee la función de enventanado de los tipos de ventana mas comunes, respuesta en frecuencia, transformada de Fourier, etc. La configuración es elegida por el usuario en un entorno amigable y de visualización atractiva. The objective of the PFC is the design and implementation of an application that works as oscilloscope, spectrum analyzer and virtual signal generator, all within the same application. Through a data acquisition card, the user can take samples of real-world signals (analog system) to generate data that can be manipulated by a computer (digital system). This same card can also generate basic signals, such as sine waves, square waves, sawtooth waves.... and further has added other functionalities as frequency modulated signals generation, Chirp signals type generation (commonly used in both sonar and radar applications, such as optical transmission) or PRN (pseudo-random noise sequence comprising a deterministic pulse that repeats every period, commonly used in GPS receivers). It also can generate widely known as Gaussian white noise signals or white noise uniform signals. The application will show in detail the acquired signals and will analyze these signals in different ways selected by the user. Windowing function has the most common window types, frequency response, Fourier transform are examples of what kind of analyzing that can be processed. The configuration is chosen by the user throught friendly and attractive displays and panels.

Algoritmos genéticos en control activo de ruido

Este proyecto se centra en la implementación de un sistema de control activo de ruido mediante algoritmos genéticos. Para ello, se ha tenido en cuenta el tipo de ruido que se quiere cancelar y el diseño del controlador, parte fundamental del sistema de control. El control activo de ruido sólo es eficaz a bajas frecuencias, hasta los 250 Hz, justo para las cuales los elementos pasivos pierden efectividad, y en zonas o recintos de pequeñas dimensiones y conductos. El controlador ha de ser capaz de seguir todas las posibles variaciones del campo acústico que puedan producirse (variaciones de fase, de frecuencia, de amplitud, de funciones de transferencia electro-acústicas, etc.). Su funcionamiento está basado en algoritmos FIR e IIR adaptativos. La elección de un tipo de filtro u otro depende de características tales como linealidad, causalidad y número de coeficientes. Para que la función de transferencia del controlador siga las variaciones que surgen en el entorno acústico de cancelación, tiene que ir variando el valor de los coeficientes del filtro mediante un algoritmo adaptativo. En este proyecto se emplea como algoritmo adaptativo un algoritmo genético, basado en la selección biológica, es decir, simulando el comportamiento evolutivo de los sistemas biológicos. Las simulaciones se han realizado con dos tipos de señales: ruido de carácter aleatorio (banda ancha) y ruido periódico (banda estrecha). En la parte final del proyecto se muestran los resultados obtenidos y las conclusiones al respecto. Summary. This project is focused on the implementation of an active noise control system using genetic algorithms. For that, it has been taken into account the noise type wanted to be canceled and the controller design, a key part of the control system. The active noise control is only effective at low frequencies, up to 250 Hz, for which the passive elements lose effectiveness, and in small areas or enclosures and ducts. The controller must be able to follow all the possible variations of the acoustic field that might be produced (phase, frequency, amplitude, electro-acoustic transfer functions, etc.). It is based on adaptive FIR and IIR algorithms. The choice of a kind of filter or another depends on characteristics like linearity, causality and number of coefficients. Moreover, the transfer function of the controller has to be changing filter coefficients value thought an adaptive algorithm. In this project a genetic algorithm is used as adaptive algorithm, based on biological selection, simulating the evolutionary behavior of biological systems. The simulations have been implemented with two signal types: random noise (broadband) and periodic noise (narrowband). In the final part of the project the results and conclusions are shown.

Dark solitons in optical communication systems

This thesis presents experimental and theoretical work on the use of dark optical solitons as data carriers in communications systems. The background chapters provide an introduction to nonlinear optics, and to dark solitons, described as intensity dips in a bright background, with an asymmetrical phase profile. The motivation for the work is explained, considering both the superior stability of dark solitons and the need for a soliton solution suitable for the normal, rather than the anomalous (bright soliton) dispersion regime. The first chapters present two generation techniques, producing packets of dark solitons via bright pulse interaction, and generating continuous trains of dark pulses using a fibre laser. The latter were not dark solitons, but were suitable for imposition of the required phase shift by virtue of their extreme stability. The later chapters focus on the propagation and control of dark solitons. Their response to periodic loss and gain is shown to result in the exponential growth of spectral sidebands. This may be suppressed by reducing the periodicity of the loss/gain cycle or using periodic filtering. A general study of the response of dark solitons to spectral filtering is undertaken, showing dramatic differences in the behaviour of black and 99.9% grey solitons. The importance of this result is highlighted by simulations of propagation in noisy systems, where the timing jitter resulting from random noise is actually enhanced by filtering. The results of using sinusoidal phase modulation to control pulse position are presented, showing that the control is at the expense of serious modulation of the bright background. It is concluded that in almost every case, dark and bright solitons have very different properties, and to continue to make comparisons would not be so productive as to develop a deeper understanding of the interactions between the dark soliton and its bright background.

Statistical physics of error-correcting codes

In this thesis we use statistical physics techniques to study the typical performance of four families of error-correcting codes based on very sparse linear transformations: Sourlas codes, Gallager codes, MacKay-Neal codes and Kanter-Saad codes. We map the decoding problem onto an Ising spin system with many-spins interactions. We then employ the replica method to calculate averages over the quenched disorder represented by the code constructions, the arbitrary messages and the random noise vectors. We find, as the noise level increases, a phase transition between successful decoding and failure phases. This phase transition coincides with upper bounds derived in the information theory literature in most of the cases. We connect the practical decoding algorithm known as probability propagation with the task of finding local minima of the related Bethe free-energy. We show that the practical decoding thresholds correspond to noise levels where suboptimal minima of the free-energy emerge. Simulations of practical decoding scenarios using probability propagation agree with theoretical predictions of the replica symmetric theory. The typical performance predicted by the thermodynamic phase transitions is shown to be attainable in computation times that grow exponentially with the system size. We use the insights obtained to design a method to calculate the performance and optimise parameters of the high performance codes proposed by Kanter and Saad.

A procedure for determining a spacewise dependent heat source and the initial temperature

The inverse problem of determining a spacewise dependent heat source, together with the initial temperature for the parabolic heat equation, using the usual conditions of the direct problem and information from two supplementary temperature measurements at different instants of time is studied. These spacewise dependent temperature measurements ensure that this inverse problem has a unique solution, despite the solution being unstable, hence the problem is ill-posed. We propose an iterative algorithm for the stable reconstruction of both the initial data and the source based on a sequence of well-posed direct problems for the parabolic heat equation, which are solved at each iteration step using the boundary element method. The instability is overcome by stopping the iterations at the first iteration for which the discrepancy principle is satisfied. Numerical results are presented for a typical benchmark test example, which has the input measured data perturbed by increasing amounts of random noise. The numerical results show that the proposed procedure gives accurate numerical approximations in relatively few iterations.

A variational method for identifying a spacewise-dependent heat source

The inverse problem of determining a spacewise-dependent heat source for the parabolic heat equation using the usual conditions of the direct problem and information from one supplementary temperature measurement at a given instant of time is studied. This spacewise-dependent temperature measurement ensures that this inverse problem has a unique solution, but the solution is unstable and hence the problem is ill-posed. We propose a variational conjugate gradient-type iterative algorithm for the stable reconstruction of the heat source based on a sequence of well-posed direct problems for the parabolic heat equation which are solved at each iteration step using the boundary element method. The instability is overcome by stopping the iterative procedure at the first iteration for which the discrepancy principle is satisfied. Numerical results are presented which have the input measured data perturbed by increasing amounts of random noise. The numerical results show that the proposed procedure yields stable and accurate numerical approximations after only a few iterations.

Determination of a spacewise dependent heat source

This paper investigates the inverse problem of determining a spacewise dependent heat source in the parabolic heat equation using the usual conditions of the direct problem and information from a supplementary temperature measurement at a given single instant of time. The spacewise dependent temperature measurement ensures that the inverse problem has a unique solution, but this solution is unstable, hence the problem is ill-posed. For this inverse problem, we propose an iterative algorithm based on a sequence of well-posed direct problems which are solved at each iteration step using the boundary element method (BEM). The instability is overcome by stopping the iterations at the first iteration for which the discrepancy principle is satisfied. Numerical results are presented for various typical benchmark test examples which have the input measured data perturbed by increasing amounts of random noise.

The Value of Knowing that You Do Not Know

The value of knowing about data availability and system accessibility is analyzed through theoretical models of Information Economics. When a user places an inquiry for information, it is important for the user to learn whether the system is not accessible or the data is not available, rather than not have any response. In reality, various outcomes can be provided by the system: nothing will be displayed to the user (e.g., a traffic light that does not operate, a browser that keeps browsing, a telephone that does not answer); a random noise will be displayed (e.g., a traffic light that displays random signals, a browser that provides disorderly results, an automatic voice message that does not clarify the situation); a special signal indicating that the system is not operating (e.g., a blinking amber indicating that the traffic light is down, a browser responding that the site is unavailable, a voice message regretting to tell that the service is not available). This article develops a model to assess the value of the information for the user in such situations by employing the information structure model prevailing in Information Economics. Examples related to data accessibility in centralized and in distributed systems are provided for illustration.

The nature of microvariability in blazar 0716+714

We organized an international campaign to observe the blazar 0716+714 in the optical band. The observations took place from February 24, 2009 to February 26, 2009. The global campaign was carried out by observers from more that sixteen countries and resulted in an extended light curve nearly seventy-eight hours long. The analysis and the modeling of this light curve form the main work of this dissertation project. In the first part of this work, we present the time series and noise analyses of the data. The time series analysis utilizes discrete Fourier transform and wavelet analysis routines to search for periods in the light curve. We then present results of the noise analysis which is based on the idea that each microvariability curve is the realization of the same underlying stochastic noise processes in the blazar jet. ^ Neither reoccuring periods nor random noise can successfully explain the observed optical fluctuations. Hence in the second part, we propose and develop a new model to account for the microvariability we see in blazar 0716+714. We propose that the microvariability is due to the emission from turbulent regions in the jet that are energized by the passage of relativistic shocks. Emission from each turbulent cell forms a pulse of emission, and when convolved with other pulses, yields the observed light curve. We use the model to obtain estimates of the physical parameters of the emission regions in the jet.^

Controladores repetitivos aplicados a filtros ativos de potência sob variações de carga e de frequência da rede

This work presents the development and modification of techniques to reduce the effects of load variation and mains frequency deviation in repetitive controllers applied to active power filters. To minimize the effects of aperiodic signals resulting from the connection or disconnection of non-linear loads is developed a technique which recognizes linear and nonlinear loads, and operates to reset the controller only when the error due to the transition of considerable value, and the transition is from non-linear to linear load. An algorithm to adapt the gain of the repetitive controller, based on a sigmoid function adaptation, in order to minimize the effects caused by random noise in the measurement system is also used. This work also analyzes the effects of frequency variation and presents the main methods to cope with this situation. Some solutions are the change in the number of samples per period and the variation of the sampling rate. The first has the advantage of using linear design techniques and results in a time invariant system. The second method changes the sampling frequency and leads to a time variant system that demands a difficult analysis of stability. The proposed algorithms were tested using the methods of truncation of the number of samples and the method of changing the sampling rate of the system to compensate possible frequency variations of the grid. Experimental results are presented to validate the proposal.

The Nature of Microvariability in Blazar 0716+714

We organized an international campaign to observe the blazar 0716+714 in the optical band. The observations took place from February 24, 2009 to February 26, 2009. The global campaign was carried out by observers from more that sixteen countries and resulted in an extended light curve nearly seventy-eight hours long. The analysis and the modeling of this light curve form the main work of this dissertation project. In the first part of this work, we present the time series and noise analyses of the data. The time series analysis utilizes discrete Fourier transform and wavelet analysis routines to search for periods in the light curve. We then present results of the noise analysis which is based on the idea that each microvariability curve is the realization of the same underlying stochastic noise processes in the blazar jet. Neither reoccuring periods nor random noise can successfully explain the observed optical fluctuations. Hence in the second part, we propose and develop a new model to account for the microvariability we see in blazar 0716+714. We propose that the microvariability is due to the emission from turbulent regions in the jet that are energized by the passage of relativistic shocks. Emission from each turbulent cell forms a pulse of emission, and when convolved with other pulses, yields the observed light curve. We use the model to obtain estimates of the physical parameters of the emission regions in the jet.

Detection of Glass pattern configurations by the primary visual cortex

The neurons in the primary visual cortex that respond to the orientation of visual stimuli were discovered in the late 1950s (Hubel, D.H. & Wiesel, T.N. 1959. J. Physiol. 148:574-591) but how they achieve this response is poorly understood. Recently, experiments have demonstrated that the visual cortex may use the image processing techniques of cross or auto-correlation to detect the streaks in random dot patterns (Barlow, H. & Berry, D.L. 2010. Proc. R. Soc. B. 278: 2069-2075). These experiments made use of sinusoidally modulated random dot patterns and of the so-called Glass patterns - where randomly positioned dot pairs are oriented in a parallel configuration (Glass, L. 1969. Nature. 223: 578-580). The image processing used by the visual cortex could be inferred from how the threshold of detection of these patterns in the presence of random noise varied as a function of the dot density in the patterns. In the present study, the detection thresholds have been measured for other types of patterns including circular, hyperbolic, spiral and radial Glass patterns and an indication of the type of image processing (cross or auto-correlation) by the visual cortex is presented. As a result, it is hoped that this study will contribute to an understanding of what David Marr called the ‘computational goal’ of the primary visual cortex (Marr, D. 1982. Vision: A Computational Investigation into the Human Representation and Processing of Visual Information. New York: Freeman.)

Simulation of the Barkhausen Noise using random field Ising model with long-range interaction

We present a method to simulate the Magnetic Barkhausen Noise using the Random Field Ising Model with magnetic long-range interaction. The method allows calculating the magnetic flux density behavior in particular sections of the lattice reticule. The results show an internal demagnetizing effect that proceeds from the magnetic long-range interactions. This demagnetizing effect induces the appearing of a magnetic pattern in the region of magnetic avalanches. When compared with the traditional method, the proposed numerical procedure neatly reduces computational costs of simulation. (c) 2008 Published by Elsevier B.V.