Projeto, desenvolvimento e implementação de um robô nadador de inspiração biológica

A elaboração deste trabalho surge no âmbito da unidade curricular de Tese/Dissertação, pertencente ao Mestrado em Engenharia Eletrotécnica e Computadores, ramo de Automação e Sistemas, do Instituto Superior de Engenharia do Porto (ISEP). Este trabalho enquadra-se no âmbito da robótica de inspiração biológica no meio aquático. Pretendeu-se com este trabalho desenvolver e implementar um robô nadador de inspiração biológica. Inicialmente foi realizado um estudo acerca da locomoção dos peixes, para perceber a sua forma de se movimentar. Foi ainda efetuado um estudo acerca dos robôs nadadores existentes, de forma a verificar a sua constituição e formas de locomoção. Numa fase inicial foi desenvolvido um protótipo e, de seguida, procedeu-se à implementação do robô de uma forma sequencial. Implementou-se a estrutura do robô, com o objetivo de se assemelhar o mais possível com um peixe biológico. Foram utilizados servomotores para a locomoção do robô. Para que o robô possua a capacidade de se movimentar numa determinada direção recorreu-se à utilização de uma bússola digital. Posteriormente introduziu-se um emissor/recetor de radiofrequência (RF) para ligar/desligar o robô. Numa fase final procederam-se aos testes da locomoção do robô. Nos ensaios realizados verificou-se que o robô conseguiu nadar com estabilidade e com sentido de direção.

Diagnosis of an EPS module

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Electrotécnica e Computadores

Investigation of ICA algorithms for feature extraction of EEG signals in discrimination of Alzheimer disease

In this paper we present a quantitative comparisons of different independent component analysis (ICA) algorithms in order to investigate their potential use in preprocessing (such as noise reduction and feature extraction) the electroencephalogram (EEG) data for early detection of Alzhemier disease (AD) or discrimination between AD (or mild cognitive impairment, MCI) and age-match control subjects.

Computational models for and from biology : simple gene assembly and reaction systems

The advancement of science and technology makes it clear that no single perspective is any longer sufficient to describe the true nature of any phenomenon. That is why the interdisciplinary research is gaining more attention overtime. An excellent example of this type of research is natural computing which stands on the borderline between biology and computer science. The contribution of research done in natural computing is twofold: on one hand, it sheds light into how nature works and how it processes information and, on the other hand, it provides some guidelines on how to design bio-inspired technologies. The first direction in this thesis focuses on a nature-inspired process called gene assembly in ciliates. The second one studies reaction systems, as a modeling framework with its rationale built upon the biochemical interactions happening within a cell. The process of gene assembly in ciliates has attracted a lot of attention as a research topic in the past 15 years. Two main modelling frameworks have been initially proposed in the end of 1990s to capture ciliates’ gene assembly process, namely the intermolecular model and the intramolecular model. They were followed by other model proposals such as templatebased assembly and DNA rearrangement pathways recombination models. In this thesis we are interested in a variation of the intramolecular model called simple gene assembly model, which focuses on the simplest possible folds in the assembly process. We propose a new framework called directed overlap-inclusion (DOI) graphs to overcome the limitations that previously introduced models faced in capturing all the combinatorial details of the simple gene assembly process. We investigate a number of combinatorial properties of these graphs, including a necessary property in terms of forbidden induced subgraphs. We also introduce DOI graph-based rewriting rules that capture all the operations of the simple gene assembly model and prove that they are equivalent to the string-based formalization of the model. Reaction systems (RS) is another nature-inspired modeling framework that is studied in this thesis. Reaction systems’ rationale is based upon two main regulation mechanisms, facilitation and inhibition, which control the interactions between biochemical reactions. Reaction systems is a complementary modeling framework to traditional quantitative frameworks, focusing on explicit cause-effect relationships between reactions. The explicit formulation of facilitation and inhibition mechanisms behind reactions, as well as the focus on interactions between reactions (rather than dynamics of concentrations) makes their applicability potentially wide and useful beyond biological case studies. In this thesis, we construct a reaction system model corresponding to the heat shock response mechanism based on a novel concept of dominance graph that captures the competition on resources in the ODE model. We also introduce for RS various concepts inspired by biology, e.g., mass conservation, steady state, periodicity, etc., to do model checking of the reaction systems based models. We prove that the complexity of the decision problems related to these properties varies from P to NP- and coNP-complete to PSPACE-complete. We further focus on the mass conservation relation in an RS and introduce the conservation dependency graph to capture the relation between the species and also propose an algorithm to list the conserved sets of a given reaction system.

Multidimensional polynomial powers of sigmoid (PPS) Wavelet neural networks

Wavelet functions have been used as the activation function in feedforward neural networks. An abundance of R&D has been produced on wavelet neural network area. Some successful algorithms and applications in wavelet neural network have been developed and reported in the literature. However, most of the aforementioned reports impose many restrictions in the classical backpropagation algorithm, such as low dimensionality, tensor product of wavelets, parameters initialization, and, in general, the output is one dimensional, etc. In order to remove some of these restrictions, a family of polynomial wavelets generated from powers of sigmoid functions is presented. We described how a multidimensional wavelet neural networks based on these functions can be constructed, trained and applied in pattern recognition tasks. As an example of application for the method proposed, it is studied the exclusive-or (XOR) problem.

DNA for nano-bio scale computation of chemical formalisms using Higher Order Logic (HOL) and analysis using an interdisciplinary approach

Bio-molecular computing, 'computations performed by bio-molecules', is already challenging traditional approaches to computation both theoretically and technologically. Often placed within the wider context of ´bio-inspired' or 'natural' or even 'unconventional' computing, the study of natural and artificial molecular computations is adding to our understanding of biology, physical sciences and computer science well beyond the framework of existing design and implementation paradigms. In this introduction, We wish to outline the current scope of the field and assemble some basic arguments that, bio-molecular computation is of central importance to computer science, physical sciences and biology using HOL - Higher Order Logic. HOL is used as the computational tool in our R&D work. DNA was analyzed as a chemical computing engine, in our effort to develop novel formalisms to understand the molecular scale bio-chemical computing behavior using HOL. In our view, our focus is one of the pioneering efforts in this promising domain of nano-bio scale chemical information processing dynamics.

A core calculus for the analysis and implementation of biologically inspired languages

The application of Concurrency Theory to Systems Biology is in its earliest stage of progress. The metaphor of cells as computing systems by Regev and Shapiro opened the employment of concurrent languages for the modelling of biological systems. Their peculiar characteristics led to the design of many bio-inspired formalisms which achieve higher faithfulness and specificity. In this thesis we present pi@, an extremely simple and conservative extension of the pi-calculus representing a keystone in this respect, thanks to its expressiveness capabilities. The pi@ calculus is obtained by the addition of polyadic synchronisation and priority to the pi-calculus, in order to achieve compartment semantics and atomicity of complex operations respectively. In its direct application to biological modelling, the stochastic variant of the calculus, Spi@, is shown able to model consistently several phenomena such as formation of molecular complexes, hierarchical subdivision of the system into compartments, inter-compartment reactions, dynamic reorganisation of compartment structure consistent with volume variation. The pivotal role of pi@ is evidenced by its capability of encoding in a compositional way several bio-inspired formalisms, so that it represents the optimal core of a framework for the analysis and implementation of bio-inspired languages. In this respect, the encodings of BioAmbients, Brane Calculi and a variant of P Systems in pi@ are formalised. The conciseness of their translation in pi@ allows their indirect comparison by means of their encodings. Furthermore it provides a ready-to-run implementation of minimal effort whose correctness is granted by the correctness of the respective encoding functions. Further important results of general validity are stated on the expressive power of priority. Several impossibility results are described, which clearly state the superior expressiveness of prioritised languages and the problems arising in the attempt of providing their parallel implementation. To this aim, a new setting in distributed computing (the last man standing problem) is singled out and exploited to prove the impossibility of providing a purely parallel implementation of priority by means of point-to-point or broadcast communication.

Expressiveness in biologically inspired languages

A very recent and exciting new area of research is the application of Concurrency Theory tools to formalize and analyze biological systems and one of the most promising approach comes from the process algebras (process calculi). A process calculus is a formal language that allows to describe concurrent systems and comes with well-established techniques for quantitative and qualitative analysis. Biological systems can be regarded as concurrent systems and therefore modeled by means of process calculi. In this thesis we focus on the process calculi approach to the modeling of biological systems and investigate, mostly from a theoretical point of view, several promising bio-inspired formalisms: Brane Calculi and k-calculus family. We provide several expressiveness results mostly by means of comparisons between calculi. We provide a lower bound to the computational power of the non Turing complete MDB Brane Calculi by showing an encoding of a simple P-System into MDB. We address the issue of local implementation within the k-calculus family: whether n-way rewrites can be simulated by binary interactions only. A solution introducing divergence is provided and we prove a deterministic solution preserving the termination property is not possible. We use the symmetric leader election problem to test synchronization capabilities within the k-calculus family. Several fragments of the original k-calculus are considered and we prove an impossibility result about encoding n-way synchronization into (n-1)-way synchronization. A similar impossibility result is obtained in a pure computer science context. We introduce CCSn, an extension of CCS with multiple input prefixes and show, using the dining philosophers problem, that there is no reasonable encoding of CCS(n+1) into CCSn.

A Motor-less and Gear-less Bio-mimetic Robotic Fish Design

In this paper, we describe our current work on bio-inspired locomotion systems using a deformable structure and smart materials, concretely Shape Memory Alloys, exploring the possibility of building motor-less and gear-less robots. A swimming underwater robot has been developed whose movements are generated using such actuators, used for bending the backbone of the fish, which in turn causes a change on the curvature of the body. This paper focuses on how standard swimming patterns can be reproduced with the proposed design, using an actuation dynamics model identified in prior work.

Bending continuous structures with SMAs: a novel robotic fish design

In this paper, we describe our research on bio-inspired locomotion systems using deformable structures and smart materials, concretely shape memory alloys (SMAs). These types of materials allow us to explore the possibility of building motor-less and gear-less robots. A swimming underwater fish-like robot has been developed whose movements are generated using SMAs. These actuators are suitable for bending the continuous backbone of the fish, which in turn causes a change in the curvature of the body. This type of structural arrangement is inspired by fish red muscles, which are mainly recruited during steady swimming for the bending of a flexible but nearly incompressible structure such as the fishbone. This paper reviews the design process of these bio-inspired structures, from the motivations and physiological inspiration to the mechatronics design, control and simulations, leading to actual experimental trials and results. The focus of this work is to present the mechanisms by which standard swimming patterns can be reproduced with the proposed design. Moreover, the performance of the SMA-based actuators’ control in terms of actuation speed and position accuracy is also addressed.

The morphofunctional approach to emotion modelling in robotics

In this conceptual paper, we discuss two areas of research in robotics, robotic models of emotion and morphofunctional machines, and we explore the scope for potential cross-fertilization between them. We shift the focus in robot models of emotion from information-theoretic aspects of appraisal to the interactive significance of bodily dispositions. Typical emotional phenomena such as arousal and action readiness can be interpreted as morphofunctional processes, and their functionality may be replicated in robotic systems with morphologies that can be modulated for real-time adaptation. We investigate the control requirements for such systems, and present a possible bio-inspired architecture, based on the division of control between neural and endocrine systems in humans and animals. We suggest that emotional epi- sodes can be understood as emergent from the coordination of action control and action-readiness, respectively. This stress on morphology complements existing research on the information-theoretic aspects of emotion.

Marco computacional para la definición de un modelo bio-inspirado en la señalización celular

Las Redes de Procesadores Evolutivos-NEP propuestas en [Mitrana et al., 2001], son un modelo computacional bio-inspirado a partir de la evolución de poblaciones de células, definiendo a nivel sintáctico algunas propiedades biológicas. En este modelo, las células están representadas por medio de palabras que describen secuencias de ADN. Informalmente, en algún instante de tiempo, el sistema evolutivo está representado por una colección de palabras cada una de las cuales representa una célula. El espacio genotipo de las especies, es un conjunto que recoge aquellas palabras que son aceptadas como sobrevivientes (es decir, como \correctas"). Desde el punto de vista de la evolución, las células pertenecen a especies y su comunidad evoluciona de acuerdo a procesos biológicos como la mutación y la división celular. éstos procesos representan el proceso natural de evolución y ponen de manifiesto una característica intrínseca de la naturaleza: el paralelismo. En este modelo, estos procesos son vistos como operaciones sobre palabras. Formalmente, el modelo de las NEP constituyen una arquitectura paralela y distribuida de procesamiento simbólico inspirada en la Máquina de conexión [Hillis, 1981], en el Paradigma de Flujo Lógico [Errico and Jesshope, 1994] y en las Redes de Procesadores Paralelos de Lenguajes (RPPL) [Csuhaj-Varju and Salomaa, 1997]. Al modelo NEP se han ido agregando nuevas y novedosas extensiones hasta el punto que actualmente podemos hablar de una familia de Redes de Procesadores Bio-inspirados (NBP) [Mitrana et al., 2012b]. Un considerable número de trabajos a lo largo de los últimos años han demostrado la potencia computacional de la familia NBP. En general, éstos modelos son computacionalmente completos, universales y eficientes [Manea et al., 2007], [Manea et al., 2010b], [Mitrana and Martín-Vide, 2005]. De acuerdo a lo anterior, se puede afirmar que el modelo NEP ha adquirido hasta el momento un nivel de madurez considerable. Sin embargo, aunque el modelo es de inspiración biológica, sus metas siguen estando motivadas en la Teoría de Lenguajes Formales y las Ciencias de la Computación. En este sentido, los aspectos biológicos han sido abordados desde una perspectiva cualitativa y el acercamiento a la realidad biológica es de forma meramente sintáctica. Para considerar estos aspectos y lograr dicho acercamiento es necesario que el modelo NEP tenga una perspectiva más amplia que incorpore la interacción de aspectos tanto cualitativos como cuantitativos. La contribución de esta Tesis puede considerarse como un paso hacia adelante en una nueva etapa de los NEPs, donde el carácter cuantitativo del modelo es de primordial interés y donde existen posibilidades de un cambio visible en el enfoque de interés del dominio de los problemas a considerar: de las ciencias de la computación hacia la simulación/modelado biológico y viceversa, entre otros. El marco computacional que proponemos en esta Tesis extiende el modelo de las Redes de Procesadores Evolutivos (NEP) y define arquitectura inspirada en la definición de bloques funcionales del proceso de señalización celular para la solución de problemas computacionales complejos y el modelado de fenómenos celulares desde una perspectiva discreta. En particular, se proponen dos extensiones: (1) los Transductores basados en Redes de Procesadores Evolutivos (NEPT), y (2) las Redes Parametrizadas de Procesadores Evolutivos Polarizados (PNPEP). La conservación de las propiedades y el poder computacional tanto de NEPT como de PNPEP se demuestra formalmente. Varias simulaciones de procesos relacionados con la señalización celular son abordadas sintáctica y computacionalmente, con el _n de mostrar la aplicabilidad e idoneidad de estas dos extensiones. ABSTRACT Network of Evolutionary Processors -NEP was proposed in [Mitrana et al., 2001], as a computational model inspired by the evolution of cell populations, which might model some properties of evolving cell communities at the syntactical level. In this model, cells are represented by words which encode their DNA sequences. Informally, at any moment of time, the evolutionary system is described by a collection of words, where each word represents one cell. Cells belong to species and their community evolves according to mutations and division which are defined by operations on words. Only those cells accepted as survivors (correct) are represented by a word in a given set of words, called the genotype space of the species. This feature is analogous with the natural process of evolution. Formally, NEP is based on an architecture for parallel and distributed processing inspired from the Connection Machine [Hillis, 1981], the Flow Logic Paradigm [Errico and Jesshope, 1994] and the Networks of Parallel Language Processors (RPPL) [Csuhaj-Varju and Salomaa, 1997]. Since the date when NEP was proposed, several extensions and variants have appeared engendering a new set of models named Networks of Bio-inspired Processors (NBP) [Mitrana et al., 2012b]. During this time, several works have proved the computational power of NBP. Specifically, their efficiency, universality, and computational completeness have been thoroughly investigated [Manea et al., 2007, Manea et al., 2010b, Mitrana and Martín-Vide, 2005]. Therefore, we can say that the NEP model has reached its maturity. Nevertheless, although the NEP model is biologically inspired, this model is mainly motivated by mathematical and computer science goals. In this context, the biological aspects are only considered from a qualitative and syntactical perspective. In view of this lack, it is important to try to keep the NEP theory as close as possible to the biological reality, extending their perspective incorporating the interplay of qualitative and quantitative aspects. The contribution of this Thesis, can be considered as a starting point in a new era of the NEP model. Then, the quantitative character of the NEP model is mandatory and it can address completely new different types of problems with respect to the classical computational domain (e.g. from the computer science to system biology). Therefore, the computational framework that we propose extends the NEP model and defines an architecture inspired by the functional blocks from cellular signaling in order to solve complex computational problems and cellular phenomena modeled from a discrete perspective. Particularly, we propose two extensions, namely: (1) Transducers based on Network of Evolutionary Processors (NEPT), and (2) Parametrized Network of Polarized Evolutionary Processors (PNPEP). Additionally, we have formally proved that the properties and computational power of NEP is kept in both extensions. Several simulations about processes related with cellular signaling both syntactical and computationally have been considered to show the model suitability.

Modelo de computación conexionista inspirado en las redes de procesadores evolutivos y su aprendizaje

La informática teórica es una disciplina básica ya que la mayoría de los avances en informática se sustentan en un sólido resultado de esa materia. En los últimos a~nos debido tanto al incremento de la potencia de los ordenadores, como a la cercanía del límite físico en la miniaturización de los componentes electrónicos, resurge el interés por modelos formales de computación alternativos a la arquitectura clásica de von Neumann. Muchos de estos modelos se inspiran en la forma en la que la naturaleza resuelve eficientemente problemas muy complejos. La mayoría son computacionalmente completos e intrínsecamente paralelos. Por este motivo se les está llegando a considerar como nuevos paradigmas de computación (computación natural). Se dispone, por tanto, de un abanico de arquitecturas abstractas tan potentes como los computadores convencionales y, a veces, más eficientes: alguna de ellas mejora el rendimiento, al menos temporal, de problemas NPcompletos proporcionando costes no exponenciales. La representación formal de las redes de procesadores evolutivos requiere de construcciones, tanto independientes, como dependientes del contexto, dicho de otro modo, en general una representación formal completa de un NEP implica restricciones, tanto sintácticas, como semánticas, es decir, que muchas representaciones aparentemente (sintácticamente) correctas de casos particulares de estos dispositivos no tendrían sentido porque podrían no cumplir otras restricciones semánticas. La aplicación de evolución gramatical semántica a los NEPs pasa por la elección de un subconjunto de ellos entre los que buscar los que solucionen un problema concreto. En este trabajo se ha realizado un estudio sobre un modelo inspirado en la biología celular denominado redes de procesadores evolutivos [55, 53], esto es, redes cuyos nodos son procesadores muy simples capaces de realizar únicamente un tipo de mutación puntual (inserción, borrado o sustitución de un símbolo). Estos nodos están asociados con un filtro que está definido por alguna condición de contexto aleatorio o de pertenencia. Las redes están formadas a lo sumo de seis nodos y, teniendo los filtros definidos por una pertenencia a lenguajes regulares, son capaces de generar todos los lenguajes enumerables recursivos independientemente del grafo subyacente. Este resultado no es sorprendente ya que semejantes resultados han sido documentados en la literatura. Si se consideran redes con nodos y filtros definidos por contextos aleatorios {que parecen estar más cerca a las implementaciones biológicas{ entonces se pueden generar lenguajes más complejos como los lenguajes no independientes del contexto. Sin embargo, estos mecanismos tan simples son capaces de resolver problemas complejos en tiempo polinomial. Se ha presentado una solución lineal para un problema NP-completo, el problema de los 3-colores. Como primer aporte significativo se ha propuesto una nueva dinámica de las redes de procesadores evolutivos con un comportamiento no determinista y masivamente paralelo [55], y por tanto todo el trabajo de investigación en el área de la redes de procesadores se puede trasladar a las redes masivamente paralelas. Por ejemplo, las redes masivamente paralelas se pueden modificar de acuerdo a determinadas reglas para mover los filtros hacia las conexiones. Cada conexión se ve como un canal bidireccional de manera que los filtros de entrada y salida coinciden. A pesar de esto, estas redes son computacionalmente completas. Se pueden también implementar otro tipo de reglas para extender este modelo computacional. Se reemplazan las mutaciones puntuales asociadas a cada nodo por la operación de splicing. Este nuevo tipo de procesador se denomina procesador splicing. Este modelo computacional de Red de procesadores con splicing ANSP es semejante en cierto modo a los sistemas distribuidos en tubos de ensayo basados en splicing. Además, se ha definido un nuevo modelo [56] {Redes de procesadores evolutivos con filtros en las conexiones{ , en el cual los procesadores tan solo tienen reglas y los filtros se han trasladado a las conexiones. Dicho modelo es equivalente, bajo determinadas circunstancias, a las redes de procesadores evolutivos clásicas. Sin dichas restricciones el modelo propuesto es un superconjunto de los NEPs clásicos. La principal ventaja de mover los filtros a las conexiones radica en la simplicidad de la modelización. Otras aportaciones de este trabajo ha sido el dise~no de un simulador en Java [54, 52] para las redes de procesadores evolutivos propuestas en esta Tesis. Sobre el término "procesador evolutivo" empleado en esta Tesis, el proceso computacional descrito aquí no es exactamente un proceso evolutivo en el sentido Darwiniano. Pero las operaciones de reescritura que se han considerado pueden interpretarse como mutaciones y los procesos de filtrado se podrían ver como procesos de selección. Además, este trabajo no abarca la posible implementación biológica de estas redes, a pesar de ser de gran importancia. A lo largo de esta tesis se ha tomado como definición de la medida de complejidad para los ANSP, una que denotaremos como tama~no (considerando tama~no como el número de nodos del grafo subyacente). Se ha mostrado que cualquier lenguaje enumerable recursivo L puede ser aceptado por un ANSP en el cual el número de procesadores está linealmente acotado por la cardinalidad del alfabeto de la cinta de una máquina de Turing que reconoce dicho lenguaje L. Siguiendo el concepto de ANSP universales introducido por Manea [65], se ha demostrado que un ANSP con una estructura de grafo fija puede aceptar cualquier lenguaje enumerable recursivo. Un ANSP se puede considerar como un ente capaz de resolver problemas, además de tener otra propiedad relevante desde el punto de vista práctico: Se puede definir un ANSP universal como una subred, donde solo una cantidad limitada de parámetros es dependiente del lenguaje. La anterior característica se puede interpretar como un método para resolver cualquier problema NP en tiempo polinomial empleando un ANSP de tama~no constante, concretamente treinta y uno. Esto significa que la solución de cualquier problema NP es uniforme en el sentido de que la red, exceptuando la subred universal, se puede ver como un programa; adaptándolo a la instancia del problema a resolver, se escogerín los filtros y las reglas que no pertenecen a la subred universal. Un problema interesante desde nuestro punto de vista es el que hace referencia a como elegir el tama~no optimo de esta red.---ABSTRACT---This thesis deals with the recent research works in the area of Natural Computing {bio-inspired models{, more precisely Networks of Evolutionary Processors first developed by Victor Mitrana and they are based on P Systems whose father is Georghe Paun. In these models, they are a set of processors connected in an underlying undirected graph, such processors have an object multiset (strings) and a set of rules, named evolution rules, that transform objects inside processors[55, 53],. These objects can be sent/received using graph connections provided they accomplish constraints defined at input and output filters processors have. This symbolic model, non deterministic one (processors are not synchronized) and massive parallel one[55] (all rules can be applied in one computational step) has some important properties regarding solution of NP-problems in lineal time and of course, lineal resources. There are a great number of variants such as hybrid networks, splicing processors, etc. that provide the model a computational power equivalent to Turing machines. The origin of networks of evolutionary processors (NEP for short) is a basic architecture for parallel and distributed symbolic processing, related to the Connection Machine as well as the Logic Flow paradigm, which consists of several processors, each of them being placed in a node of a virtual complete graph, which are able to handle data associated with the respective node. All the nodes send simultaneously their data and the receiving nodes handle also simultaneously all the arriving messages, according to some strategies. In a series of papers one considers that each node may be viewed as a cell having genetic information encoded in DNA sequences which may evolve by local evolutionary events, that is point mutations. Each node is specialized just for one of these evolutionary operations. Furthermore, the data in each node is organized in the form of multisets of words (each word appears in an arbitrarily large number of copies), and all the copies are processed in parallel such that all the possible events that can take place do actually take place. Obviously, the computational process just described is not exactly an evolutionary process in the Darwinian sense. But the rewriting operations we have considered might be interpreted as mutations and the filtering process might be viewed as a selection process. Recombination is missing but it was asserted that evolutionary and functional relationships between genes can be captured by taking only local mutations into consideration. It is clear that filters associated with each node allow a strong control of the computation. Indeed, every node has an input and output filter; two nodes can exchange data if it passes the output filter of the sender and the input filter of the receiver. Moreover, if some data is sent out by some node and not able to enter any node, then it is lost. In this paper we simplify the ANSP model considered in by moving the filters from the nodes to the edges. Each edge is viewed as a two-way channel such that the input and output filters coincide. Clearly, the possibility of controlling the computation in such networks seems to be diminished. For instance, there is no possibility to loose data during the communication steps. In spite of this and of the fact that splicing is not a powerful operation (remember that splicing systems generates only regular languages) we prove here that these devices are computationally complete. As a consequence, we propose characterizations of two complexity classes, namely NP and PSPACE, in terms of accepting networks of restricted splicing processors with filtered connections. We proposed a uniform linear time solution to SAT based on ANSPFCs with linearly bounded resources. This solution should be understood correctly: we do not solve SAT in linear time and space. Since any word and auxiliary word appears in an arbitrarily large number of copies, one can generate in linear time, by parallelism and communication, an exponential number of words each of them having an exponential number of copies. However, this does not seem to be a major drawback since by PCR (Polymerase Chain Reaction) one can generate an exponential number of identical DNA molecules in a linear number of reactions. It is worth mentioning that the ANSPFC constructed above remains unchanged for any instance with the same number of variables. Therefore, the solution is uniform in the sense that the network, excepting the input and output nodes, may be viewed as a program according to the number of variables, we choose the filters, the splicing words and the rules, then we assign all possible values to the variables, and compute the formula.We proved that ANSP are computationally complete. Do the ANSPFC remain still computationally complete? If this is not the case, what other problems can be eficiently solved by these ANSPFCs? Moreover, the complexity class NP is exactly the class of all languages decided by ANSP in polynomial time. Can NP be characterized in a similar way with ANSPFCs?

Contributions to the Resilience Management in the Internet of Things

El auge del "Internet de las Cosas" (IoT, "Internet of Things") y sus tecnologías asociadas han permitido su aplicación en diversos dominios de la aplicación, entre los que se encuentran la monitorización de ecosistemas forestales, la gestión de catástrofes y emergencias, la domótica, la automatización industrial, los servicios para ciudades inteligentes, la eficiencia energética de edificios, la detección de intrusos, la gestión de desastres y emergencias o la monitorización de señales corporales, entre muchas otras. La desventaja de una red IoT es que una vez desplegada, ésta queda desatendida, es decir queda sujeta, entre otras cosas, a condiciones climáticas cambiantes y expuestas a catástrofes naturales, fallos de software o hardware, o ataques maliciosos de terceros, por lo que se puede considerar que dichas redes son propensas a fallos. El principal requisito de los nodos constituyentes de una red IoT es que estos deben ser capaces de seguir funcionando a pesar de sufrir errores en el propio sistema. La capacidad de la red para recuperarse ante fallos internos y externos inesperados es lo que se conoce actualmente como "Resiliencia" de la red. Por tanto, a la hora de diseñar y desplegar aplicaciones o servicios para IoT, se espera que la red sea tolerante a fallos, que sea auto-configurable, auto-adaptable, auto-optimizable con respecto a nuevas condiciones que puedan aparecer durante su ejecución. Esto lleva al análisis de un problema fundamental en el estudio de las redes IoT, el problema de la "Conectividad". Se dice que una red está conectada si todo par de nodos en la red son capaces de encontrar al menos un camino de comunicación entre ambos. Sin embargo, la red puede desconectarse debido a varias razones, como que se agote la batería, que un nodo sea destruido, etc. Por tanto, se hace necesario gestionar la resiliencia de la red con el objeto de mantener la conectividad entre sus nodos, de tal manera que cada nodo IoT sea capaz de proveer servicios continuos, a otros nodos, a otras redes o, a otros servicios y aplicaciones. En este contexto, el objetivo principal de esta tesis doctoral se centra en el estudio del problema de conectividad IoT, más concretamente en el desarrollo de modelos para el análisis y gestión de la Resiliencia, llevado a la práctica a través de las redes WSN, con el fin de mejorar la capacidad la tolerancia a fallos de los nodos que componen la red. Este reto se aborda teniendo en cuenta dos enfoques distintos, por una parte, a diferencia de otro tipo de redes de dispositivos convencionales, los nodos en una red IoT son propensos a perder la conexión, debido a que se despliegan en entornos aislados, o en entornos con condiciones extremas; por otra parte, los nodos suelen ser recursos con bajas capacidades en términos de procesamiento, almacenamiento y batería, entre otros, por lo que requiere que el diseño de la gestión de su resiliencia sea ligero, distribuido y energéticamente eficiente. En este sentido, esta tesis desarrolla técnicas auto-adaptativas que permiten a una red IoT, desde la perspectiva del control de su topología, ser resiliente ante fallos en sus nodos. Para ello, se utilizan técnicas basadas en lógica difusa y técnicas de control proporcional, integral y derivativa (PID - "proportional-integral-derivative"), con el objeto de mejorar la conectividad de la red, teniendo en cuenta que el consumo de energía debe preservarse tanto como sea posible. De igual manera, se ha tenido en cuenta que el algoritmo de control debe ser distribuido debido a que, en general, los enfoques centralizados no suelen ser factibles a despliegues a gran escala. El presente trabajo de tesis implica varios retos que conciernen a la conectividad de red, entre los que se incluyen: la creación y el análisis de modelos matemáticos que describan la red, una propuesta de sistema de control auto-adaptativo en respuesta a fallos en los nodos, la optimización de los parámetros del sistema de control, la validación mediante una implementación siguiendo un enfoque de ingeniería del software y finalmente la evaluación en una aplicación real. Atendiendo a los retos anteriormente mencionados, el presente trabajo justifica, mediante una análisis matemático, la relación existente entre el "grado de un nodo" (definido como el número de nodos en la vecindad del nodo en cuestión) y la conectividad de la red, y prueba la eficacia de varios tipos de controladores que permiten ajustar la potencia de trasmisión de los nodos de red en respuesta a eventuales fallos, teniendo en cuenta el consumo de energía como parte de los objetivos de control. Así mismo, este trabajo realiza una evaluación y comparación con otros algoritmos representativos; en donde se demuestra que el enfoque desarrollado es más tolerante a fallos aleatorios en los nodos de la red, así como en su eficiencia energética. Adicionalmente, el uso de algoritmos bioinspirados ha permitido la optimización de los parámetros de control de redes dinámicas de gran tamaño. Con respecto a la implementación en un sistema real, se han integrado las propuestas de esta tesis en un modelo de programación OSGi ("Open Services Gateway Initiative") con el objeto de crear un middleware auto-adaptativo que mejore la gestión de la resiliencia, especialmente la reconfiguración en tiempo de ejecución de componentes software cuando se ha producido un fallo. Como conclusión, los resultados de esta tesis doctoral contribuyen a la investigación teórica y, a la aplicación práctica del control resiliente de la topología en redes distribuidas de gran tamaño. Los diseños y algoritmos presentados pueden ser vistos como una prueba novedosa de algunas técnicas para la próxima era de IoT. A continuación, se enuncian de forma resumida las principales contribuciones de esta tesis: (1) Se han analizado matemáticamente propiedades relacionadas con la conectividad de la red. Se estudia, por ejemplo, cómo varía la probabilidad de conexión de la red al modificar el alcance de comunicación de los nodos, así como cuál es el mínimo número de nodos que hay que añadir al sistema desconectado para su re-conexión. (2) Se han propuesto sistemas de control basados en lógica difusa para alcanzar el grado de los nodos deseado, manteniendo la conectividad completa de la red. Se han evaluado diferentes tipos de controladores basados en lógica difusa mediante simulaciones, y los resultados se han comparado con otros algoritmos representativos. (3) Se ha investigado más a fondo, dando un enfoque más simple y aplicable, el sistema de control de doble bucle, y sus parámetros de control se han optimizado empleando algoritmos heurísticos como el método de la entropía cruzada (CE, "Cross Entropy"), la optimización por enjambre de partículas (PSO, "Particle Swarm Optimization"), y la evolución diferencial (DE, "Differential Evolution"). (4) Se han evaluado mediante simulación, la mayoría de los diseños aquí presentados; además, parte de los trabajos se han implementado y validado en una aplicación real combinando técnicas de software auto-adaptativo, como por ejemplo las de una arquitectura orientada a servicios (SOA, "Service-Oriented Architecture"). ABSTRACT The advent of the Internet of Things (IoT) enables a tremendous number of applications, such as forest monitoring, disaster management, home automation, factory automation, smart city, etc. However, various kinds of unexpected disturbances may cause node failure in the IoT, for example battery depletion, software/hardware malfunction issues and malicious attacks. So, it can be considered that the IoT is prone to failure. The ability of the network to recover from unexpected internal and external failures is known as "resilience" of the network. Resilience usually serves as an important non-functional requirement when designing IoT, which can further be broken down into "self-*" properties, such as self-adaptive, self-healing, self-configuring, self-optimization, etc. One of the consequences that node failure brings to the IoT is that some nodes may be disconnected from others, such that they are not capable of providing continuous services for other nodes, networks, and applications. In this sense, the main objective of this dissertation focuses on the IoT connectivity problem. A network is regarded as connected if any pair of different nodes can communicate with each other either directly or via a limited number of intermediate nodes. More specifically, this thesis focuses on the development of models for analysis and management of resilience, implemented through the Wireless Sensor Networks (WSNs), which is a challenging task. On the one hand, unlike other conventional network devices, nodes in the IoT are more likely to be disconnected from each other due to their deployment in a hostile or isolated environment. On the other hand, nodes are resource-constrained in terms of limited processing capability, storage and battery capacity, which requires that the design of the resilience management for IoT has to be lightweight, distributed and energy-efficient. In this context, the thesis presents self-adaptive techniques for IoT, with the aim of making the IoT resilient against node failures from the network topology control point of view. The fuzzy-logic and proportional-integral-derivative (PID) control techniques are leveraged to improve the network connectivity of the IoT in response to node failures, meanwhile taking into consideration that energy consumption must be preserved as much as possible. The control algorithm itself is designed to be distributed, because the centralized approaches are usually not feasible in large scale IoT deployments. The thesis involves various aspects concerning network connectivity, including: creation and analysis of mathematical models describing the network, proposing self-adaptive control systems in response to node failures, control system parameter optimization, implementation using the software engineering approach, and evaluation in a real application. This thesis also justifies the relations between the "node degree" (the number of neighbor(s) of a node) and network connectivity through mathematic analysis, and proves the effectiveness of various types of controllers that can adjust power transmission of the IoT nodes in response to node failures. The controllers also take into consideration the energy consumption as part of the control goals. The evaluation is performed and comparison is made with other representative algorithms. The simulation results show that the proposals in this thesis can tolerate more random node failures and save more energy when compared with those representative algorithms. Additionally, the simulations demonstrate that the use of the bio-inspired algorithms allows optimizing the parameters of the controller. With respect to the implementation in a real system, the programming model called OSGi (Open Service Gateway Initiative) is integrated with the proposals in order to create a self-adaptive middleware, especially reconfiguring the software components at runtime when failures occur. The outcomes of this thesis contribute to theoretic research and practical applications of resilient topology control for large and distributed networks. The presented controller designs and optimization algorithms can be viewed as novel trials of the control and optimization techniques for the coming era of the IoT. The contributions of this thesis can be summarized as follows: (1) Mathematically, the fault-tolerant probability of a large-scale stochastic network is analyzed. It is studied how the probability of network connectivity depends on the communication range of the nodes, and what is the minimum number of neighbors to be added for network re-connection. (2) A fuzzy-logic control system is proposed, which obtains the desired node degree and in turn maintains the network connectivity when it is subject to node failures. There are different types of fuzzy-logic controllers evaluated by simulations, and the results demonstrate the improvement of fault-tolerant capability as compared to some other representative algorithms. (3) A simpler but more applicable approach, the two-loop control system is further investigated, and its control parameters are optimized by using some heuristic algorithms such as Cross Entropy (CE), Particle Swarm Optimization (PSO), and Differential Evolution (DE). (4) Most of the designs are evaluated by means of simulations, but part of the proposals are implemented and tested in a real-world application by combining the self-adaptive software technique and the control algorithms which are presented in this thesis.

Current status of gene therapy for breast cancer: progress and challenges

Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development.