Ensemble transcript interaction networks: A case study on Alzheimer's disease

Systems biology techniques are a topic of recent interest within the neurological field. Computational intelligence (CI) addresses this holistic perspective by means of consensus or ensemble techniques ultimately capable of uncovering new and relevant findings. In this paper, we propose the application of a CI approach based on ensemble Bayesian network classifiers and multivariate feature subset selection to induce probabilistic dependences that could match or unveil biological relationships. The research focuses on the analysis of high-throughput Alzheimer's disease (AD) transcript profiling. The analysis is conducted from two perspectives. First, we compare the expression profiles of hippocampus subregion entorhinal cortex (EC) samples of AD patients and controls. Second, we use the ensemble approach to study four types of samples: EC and dentate gyrus (DG) samples from both patients and controls. Results disclose transcript interaction networks with remarkable structures and genes not directly related to AD by previous studies. The ensemble is able to identify a variety of transcripts that play key roles in other neurological pathologies. Classical statistical assessment by means of non-parametric tests confirms the relevance of the majority of the transcripts. The ensemble approach pinpoints key metabolic mechanisms that could lead to new findings in the pathogenesis and development of AD

Human-robot interaction for telemanipulation in large workspaces

Independientemente de la existencia de técnicas altamente sofisticadas y capacidades de cómputo cada vez más elevadas, los problemas asociados a los robots que interactúan con entornos no estructurados siguen siendo un desafío abierto en robótica. A pesar de los grandes avances de los sistemas robóticos autónomos, hay algunas situaciones en las que una persona en el bucle sigue siendo necesaria. Ejemplos de esto son, tareas en entornos de fusión nuclear, misiones espaciales, operaciones submarinas y cirugía robótica. Esta necesidad se debe a que las tecnologías actuales no pueden realizar de forma fiable y autónoma cualquier tipo de tarea. Esta tesis presenta métodos para la teleoperación de robots abarcando distintos niveles de abstracción que van desde el control supervisado, en el que un operador da instrucciones de alto nivel en la forma de acciones, hasta el control bilateral, donde los comandos toman la forma de señales de control de bajo nivel. En primer lugar, se presenta un enfoque para llevar a cabo la teleoperación supervisada de robots humanoides. El objetivo es controlar robots terrestres capaces de ejecutar tareas complejas en entornos de búsqueda y rescate utilizando enlaces de comunicación limitados. Esta propuesta incorpora comportamientos autónomos que el operador puede utilizar para realizar tareas de navegación y manipulación mientras se permite cubrir grandes áreas de entornos remotos diseñados para el acceso de personas. Los resultados experimentales demuestran la eficacia de los métodos propuestos. En segundo lugar, se investiga el uso de dispositivos rentables para telemanipulación guiada. Se presenta una aplicación que involucra un robot humanoide bimanual y un traje de captura de movimiento basado en sensores inerciales. En esta aplicación, se estudian las capacidades de adaptación introducidas por el factor humano y cómo estas pueden compensar la falta de sistemas robóticos de alta precisión. Este trabajo es el resultado de una colaboración entre investigadores del Biorobotics Laboratory de la Universidad de Harvard y el Centro de Automática y Robótica UPM-CSIC. En tercer lugar, se presenta un nuevo controlador háptico que combina velocidad y posición. Este controlador bilateral híbrido hace frente a los problemas relacionados con la teleoperación de un robot esclavo con un gran espacio de trabajo usando un dispositivo háptico pequeño como maestro. Se pueden cubrir amplias áreas de trabajo al cambiar automáticamente entre los modos de control de velocidad y posición. Este controlador háptico es ideal para sistemas maestro-esclavo con cinemáticas diferentes, donde los comandos se transmiten en el espacio de la tarea del entorno remoto. El método es validado para realizar telemanipulación hábil de objetos con un robot industrial. Por último, se introducen dos contribuciones en el campo de la manipulación robótica. Por un lado, se presenta un nuevo algoritmo de cinemática inversa, llamado método iterativo de desacoplamiento cinemático. Este método se ha desarrollado para resolver el problema cinemático inverso de un tipo de robot de seis grados de libertad donde una solución cerrada no está disponible. La eficacia del método se compara con métodos numéricos convencionales. Además, se ha diseñado una taxonomía robusta de agarres que permite controlar diferentes manos robóticas utilizando una correspondencia, basada en gestos, entre los espacios de trabajo de la mano humana y de la mano robótica. El gesto de la mano humana se identifica mediante la lectura de los movimientos relativos del índice, el pulgar y el dedo medio del usuario durante las primeras etapas del agarre. ABSTRACT Regardless of the availability of highly sophisticated techniques and ever increasing computing capabilities, the problems associated with robots interacting with unstructured environments remains an open challenge. Despite great advances in autonomous robotics, there are some situations where a humanin- the-loop is still required, such as, nuclear, space, subsea and robotic surgery operations. This is because the current technologies cannot reliably perform all kinds of task autonomously. This thesis presents methods for robot teleoperation strategies at different levels of abstraction ranging from supervisory control, where the operator gives high-level task actions, to bilateral teleoperation, where the commands take the form of low-level control inputs. These strategies contribute to improve the current human-robot interfaces specially in the case of slave robots deployed at large workspaces. First, an approach to perform supervisory teleoperation of humanoid robots is presented. The goal is to control ground robots capable of executing complex tasks in disaster relief environments under constrained communication links. This proposal incorporates autonomous behaviors that the operator can use to perform navigation and manipulation tasks which allow covering large human engineered areas of the remote environment. The experimental results demonstrate the efficiency of the proposed methods. Second, the use of cost-effective devices for guided telemanipulation is investigated. A case study involving a bimanual humanoid robot and an Inertial Measurement Unit (IMU) Motion Capture (MoCap) suit is introduced. Herein, it is corroborated how the adaptation capabilities offered by the human-in-the-loop factor can compensate for the lack of high-precision robotic systems. This work is the result of collaboration between researchers from the Harvard Biorobotics Laboratory and the Centre for Automation and Robotics UPM-CSIC. Thirdly, a new haptic rate-position controller is presented. This hybrid bilateral controller copes with the problems related to the teleoperation of a slave robot with large workspace using a small haptic device as master. Large workspaces can be covered by automatically switching between rate and position control modes. This haptic controller is ideal to couple kinematic dissimilar master-slave systems where the commands are transmitted in the task space of the remote environment. The method is validated to perform dexterous telemanipulation of objects with a robotic manipulator. Finally, two contributions for robotic manipulation are introduced. First, a new algorithm, the Iterative Kinematic Decoupling method, is presented. It is a numeric method developed to solve the Inverse Kinematics (IK) problem of a type of six-DoF robotic arms where a close-form solution is not available. The effectiveness of this IK method is compared against conventional numerical methods. Second, a robust grasp mapping has been conceived. It allows to control a wide range of different robotic hands using a gesture based correspondence between the human hand space and the robotic hand space. The human hand gesture is identified by reading the relative movements of the index, thumb and middle fingers of the user during the early stages of grasping.

Caracterización de sistemas vibroacústicos mediante análisis estadístico de energía

Hoy día nadie discute la importancia de predecir el comportamiento vibroacústico de estructuras (edificios, vehículos aeronaves, satélites). También se ha hecho patente, con el tiempo, que el rango espectral en el que la respuesta es importante se ha desplazado hacia alta frecuencia en prácticamente todos los campos. Esto ha hecho que los métodos de análisis en este rango alto de frecuencias cobren importancia y actualidad. Uno de los métodos más extendidos para este fin es el basado en el Análisis Estadístico de la Energía, SEA. Es un método que ha mostrado proporcionar un buen equilibrio entre potencia de calculo, precisión y fiabilidad. En un SEA el sistema (estructura, cavidades o aire circundante) se modela mediante una matriz de coeficientes que dependen directamente de los factores de pérdidas de las distintas partes del sistema. Formalmente es un método de análisis muy cómodo e intuitivo de manejar cuya mayor dificultad es precisamente la determinación de esos factores de pérdidas. El catálogo de expresiones analíticas o numéricas para su determinación no es suficientemente amplio por lo que normalmente siempre se suele acabar necesitando hacer uso de herramientas experimentales, ya sea para su obtención o la comprobación de los valores utilizados. La determinación experimental tampoco está exenta de problemas, su obtención necesita de configuraciones experimentales grandes y complejas con requisitos que pueden llegar a ser muy exigentes y en las que además, se ven involucrados problemas numéricos relacionados con los valores de los propios factores de pérdidas, el valor relativo entre ellos y las características de las matrices que conforman. Este trabajo estudia la caracterización de sistemas vibroacústicos mediante el análisis estadístico de energía. Se centra en la determinación precisa de los valores de los factores de pérdidas. Dados los problemas que puede presentar un sistema experimental de estas características, en una primera parte se estudia la influencia de todas las magnitudes que intervienen en la determinación de los factores de pérdidas mediante un estudio de incertidumbres relativas, que, por medio de los coeficientes de sensibilidad normalizados, indicará la importancia de cada una de las magnitudes de entrada (esencialmente energías y potencias) en los resultados. De esta parte se obtiene una visión general sobre a qué mensurados se debe prestar más atención, y de qué problemas pueden ser los que más influyan en la falta de estabilidad (o incoherencia) de los resultados. Además, proporciona un modelo de incertidumbres válido para los casos estudiados y ha permitido evaluar el error cometido por algún método utilizado habitualmente para la caracterización de factores de pérdidas como la aproximación a 2 subsistemas En una segunda parte se hace uso de las conclusiones obtenidas en la primera, de forma que el trabajo se orienta en dos direcciones. Una dirigida a la determi nación suficientemente fiel de la potencia de entrada que permita simplificar en lo posible la configuración experimental. Otra basada en un análisis detallado de las propiedades de la matriz que caracteriza un SEA y que conduce a la propuesta de un método para su determinación robusta, basada en un filtrado de Montecarlo y que, además, muestra cómo los problemas numéricos de la matriz SEA pueden no ser tan insalvables como se apunta en la literatura. Por último, además, se plantea una solución al caso en el que no todos los subsistemas en los que se divide el sistema puedan ser excitados. El método propuesto aquí no permite obtener el conjunto completo de coeficientes necesarios para definir un sistema, pero el solo hecho de poder obtener conjuntos parciales ya es un avance importante y, sobre todo, abre la puerta al desarrollo de métodos que permitan relajar de forma importante las exigencias que la determinación experimental de matrices SEA tiene. ABSTRACT At present there is an agreement about the importance to predict the vibroacoustic response of structures (buildings, vehicles, aircrafts, satellites, etc.). In addition, there has become clear over the time that the frequency range over which the response is important has been shift to higher frequencies in almost all the engineering fields. As a consequence, the numerical methods for high frequency analysis have increase in importance. One the most widespread methods for this type of analysis is the one based on the Statistical Energy Analysis, SEA. This method has shown to provide a good balance among calculation power, accuracy and liability. Within a SEA, a system (structure, cavities, surrounding air) is modeled by a coefficients matrix that depends directly on the loss factors of the different parts of the system. Formally, SEA is a very handy and intuitive analysis method whose greatest handicap is precisely the determination of the loss factors. The existing set of analytical or numerical equations to obtain the loss factor values is not enough, so that usually it is necessary to use experimental techniques whether it is to its determination to to check the estimated values by another mean. The experimental determination presents drawbacks, as well. To obtain them great and complex experimental setups are needed including requirements that can be very demanding including numerical problems related to the values of the loss factors themselves, their relative value and the characteristics of the matrices they define. The present work studies the characterization of vibroacousti systems by this SEA method. It focuses on the accurate determination of the loss factors values. Given all the problems an experimental setup of these characteristics can show, the work is divided in two parts. In the first part, the influence of all the quantities involved on the determination of the loss factors is studied by a relative uncertainty estimation, which, by means of the normalised sensitivity coefficients, will provide an insight about the importance of every input quantities (energies and input powers, mainly) on the final result. Besides, this part, gives an uncertainty model that has allowed assessing the error of one of the methods more widely used to characterize the loss factors: the 2-subsystem approach. In the second part, use of the former conclusions is used. An equation for the input power into the subsystems is proposed. This equation allows simplifying the experimental setup without changing the liability of the test. A detailed study of the SEA matrix properties leads to propose a robust determination method of this SEA matrix by a Monte Carlo filtering. In turn, this new method shows how the numerical problems of the SEA matrix can be overcome Finally, a solution is proposed for the case where not all the subsystems are excited. The method proposed do not allows obtaining the whole set of coefficients of the SEA matrix, but the simple fact of getting partial sets of loss factors is a significant advance and, over all, it opens the door to the development of new methods that loosen the requirements that an experimental determination of a SEA matrix have.

Feasibility assessment of the interactive use of a Monte Carlo algorithm in treatment planning for intraoperative electron radiation therapy

This work analysed the feasibility of using a fast, customized Monte Carlo (MC) method to perform accurate computation of dose distributions during pre- and intraplanning of intraoperative electron radiation therapy (IOERT) procedures. The MC method that was implemented, which has been integrated into a specific innovative simulation and planning tool, is able to simulate the fate of thousands of particles per second, and it was the aim of this work to determine the level of interactivity that could be achieved. The planning workflow enabled calibration of the imaging and treatment equipment, as well as manipulation of the surgical frame and insertion of the protection shields around the organs at risk and other beam modifiers. In this way, the multidisciplinary team involved in IOERT has all the tools necessary to perform complex MC dosage simulations adapted to their equipment in an efficient and transparent way. To assess the accuracy and reliability of this MC technique, dose distributions for a monoenergetic source were compared with those obtained using a general-purpose software package used widely in medical physics applications. Once accuracy of the underlying simulator was confirmed, a clinical accelerator was modelled and experimental measurements in water were conducted. A comparison was made with the output from the simulator to identify the conditions under which accurate dose estimations could be obtained in less than 3 min, which is the threshold imposed to allow for interactive use of the tool in treatment planning. Finally, a clinically relevant scenario, namely early-stage breast cancer treatment, was simulated with pre- and intraoperative volumes to verify that it was feasible to use the MC tool intraoperatively and to adjust dose delivery based on the simulation output, without compromising accuracy. The workflow provided a satisfactory model of the treatment head and the imaging system, enabling proper configuration of the treatment planning system and providing good accuracy in the dosage simulation.

MedVir: an interactive representation system of multidimensional medical data applied to Traumatic Brain Injury's rehabilitation prediction

Clinicians could model the brain injury of a patient through his brain activity. However, how this model is defined and how it changes when the patient is recovering are questions yet unanswered. In this paper, the use of MedVir framework is proposed with the aim of answering these questions. Based on complex data mining techniques, this provides not only the differentiation between TBI patients and control subjects (with a 72% of accuracy using 0.632 Bootstrap validation), but also the ability to detect whether a patient may recover or not, and all of that in a quick and easy way through a visualization technique which allows interaction.