13 resultados para Feedback Repression

em Universidad Politécnica de Madrid


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Exploiting the full potential of telemedical systems means using platform based solutions: data are recovered from biomedical sensors, hospital information systems, care-givers, as well as patients themselves, and are processed and redistributed in an either centralized or, more probably, decentralized way. The integration of all these different devices, and interfaces, as well as the automated analysis and representation of all the pieces of information are current key challenges in telemedicine. Mobile phone technology has just begun to offer great opportunities of using this diverse information for guiding, warning, and educating patients, thus increasing their autonomy and adherence to their prescriptions. However, most of these existing mobile solutions are not based on platform systems and therefore represent limited, isolated applications. This article depicts how telemedical systems, based on integrated health data platforms, can maximize prescription adherence in chronic patients through mobile feedback. The application described here has been developed in an EU-funded R&D project called METABO, dedicated to patients with type 1 or type 2 Diabetes Mellitus

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DynaLearn (http://www.DynaLearn.eu) develops a cognitive artefact that engages learners in an active learning by modelling process to develop conceptual system knowledge. Learners create external representations using diagrams. The diagrams capture conceptual knowledge using the Garp3 Qualitative Reasoning (QR) formalism [2]. The expressions can be simulated, confronting learners with the logical consequences thereof. To further aid learners, DynaLearn employs a sequence of knowledge representations (Learning Spaces, LS), with increasing complexity in terms of the modelling ingredients a learner can use [1]. An online repository contains QR models created by experts/teachers and learners. The server runs semantic services [4] to generate feedback at the request of learners via the workbench. The feedback is communicated to the learner via a set of virtual characters, each having its own competence [3]. A specific feedback thus incorporates three aspects: content, character appearance, and a didactic setting (e.g. Quiz mode). In the interactive event we will demonstrate the latest achievements of the DynaLearn project. First, the 6 learning spaces for learners to work with. Second, the generation of feedback relevant to the individual needs of a learner using Semantic Web technology. Third, the verbalization of the feedback via different animated virtual characters, notably: Basic help, Critic, Recommender, Quizmaster & Teachable agen

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Introduction and motivation: A wide variety of organisms have developed in-ternal biomolecular clocks in order to adapt to cyclic changes of the environment. Clock operation involves genetic networks. These genetic networks have to be mod¬eled in order to understand the underlying mechanism of oscillations and to design new synthetic cellular clocks. This doctoral thesis has resulted in two contributions to the fields of genetic clocks and systems and synthetic biology, generally. The first contribution is a new genetic circuit model that exhibits an oscillatory behav¬ior through catalytic RNA molecules. The second and major contribution is a new genetic circuit model demonstrating that a repressor molecule acting on the positive feedback of a self-activating gene produces reliable oscillations. First contribution: A new model of a synthetic genetic oscillator based on a typical two-gene motif with one positive and one negative feedback loop is pre¬sented. The originality is that the repressor is a catalytic RNA molecule rather than a protein or a non-catalytic RNA molecule. This catalytic RNA is a ribozyme that acts post-transcriptionally by binding to and cleaving target mRNA molecules. This genetic clock involves just two genes, a mRNA and an activator protein, apart from the ribozyme. Parameter values that produce a circadian period in both determin¬istic and stochastic simulations have been chosen as an example of clock operation. The effects of the stochastic fluctuations are quantified by a period histogram and autocorrelation function. The conclusion is that catalytic RNA molecules can act as repressor proteins and simplify the design of genetic oscillators. Second and major contribution: It is demonstrated that a self-activating gene in conjunction with a simple negative interaction can easily produce robust matically validated. This model is comprised of two clearly distinct parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the oscillator dynamics are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this study is that a simple and usual negative interaction, such as degradation, se¬questration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. At the genetic level, this means that an explicit negative feedback loop is not necessary. Unlike many genetic oscillators, this model needs neither cooperative binding reactions nor the formation of protein multimers. Applications and future research directions: Recently, RNA molecules have been found to play many new catalytic roles. The first oscillatory genetic model proposed in this thesis uses ribozymes as repressor molecules. This could provide new synthetic biology design principles and a better understanding of cel¬lular clocks regulated by RNA molecules. The second genetic model proposed here involves only a repression acting on a self-activating gene and produces robust oscil¬lations. Unlike current two-gene oscillators, this model surprisingly does not require a second repressor gene. This result could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators. Possible follow-on research directions are: validate models in vivo and in vitro, research the potential of second model as a genetic memory, investigate new genetic oscillators regulated by non-coding RNAs and design a biosensor of positive feedbacks in genetic networks based on the operation of the second model Resumen Introduccion y motivacion: Una amplia variedad de organismos han desarro-llado relojes biomoleculares internos con el fin de adaptarse a los cambios ciclicos del entorno. El funcionamiento de estos relojes involucra redes geneticas. El mo delado de estas redes geneticas es esencial tanto para entender los mecanismos que producen las oscilaciones como para diseiiar nuevos circuitos sinteticos en celulas. Esta tesis doctoral ha dado lugar a dos contribuciones dentro de los campos de los circuitos geneticos en particular, y biologia de sistemas y sintetica en general. La primera contribucion es un nuevo modelo de circuito genetico que muestra un comportamiento oscilatorio usando moleculas de ARN cataliticas. La segunda y principal contribucion es un nuevo modelo de circuito genetico que demuestra que una molecula represora actuando sobre el lazo de un gen auto-activado produce oscilaciones robustas. Primera contribucion: Es un nuevo modelo de oscilador genetico sintetico basado en una tipica red genetica compuesta por dos genes con dos lazos de retroa-limentacion, uno positivo y otro negativo. La novedad de este modelo es que el represor es una molecula de ARN catalftica, en lugar de una protefna o una molecula de ARN no-catalitica. Este ARN catalitico es una ribozima que actua despues de la transcription genetica uniendose y cortando moleculas de ARN mensajero (ARNm). Este reloj genetico involucra solo dos genes, un ARNm y una proteina activadora, aparte de la ribozima. Como ejemplo de funcionamiento, se han escogido valores de los parametros que producen oscilaciones con periodo circadiano (24 horas) tanto en simulaciones deterministas como estocasticas. El efecto de las fluctuaciones es-tocasticas ha sido cuantificado mediante un histograma del periodo y la función de auto-correlacion. La conclusion es que las moleculas de ARN con propiedades cataliticas pueden jugar el misnio papel que las protemas represoras, y por lo tanto, simplificar el diseno de los osciladores geneticos. Segunda y principal contribucion: Es un nuevo modelo de oscilador genetico que demuestra que un gen auto-activado junto con una simple interaction negativa puede producir oscilaciones robustas. Este modelo ha sido estudiado y validado matematicamente. El modelo esta compuesto de dos partes bien diferenciadas. La primera parte es un lazo de retroalimentacion positiva creado por una proteina que se une al promotor de su propio gen activando la transcription. La segunda parte es una interaction negativa en la que una molecula represora evita la union de la proteina con el promotor. Un estudio estocastico muestra que el sistema es robusto al ruido. Un estudio determinista muestra que la dinamica del sistema es debida principalmente a dos tipos de biomoleculas: la proteina, y el complejo formado por el represor y esta proteina. La conclusion principal de este estudio es que una simple y usual interaction negativa, tal como una degradation, un secuestro o una inhibition, actuando sobre el lazo de retroalimentacion positiva de un solo gen es una condition suficiente para producir oscilaciones robustas. Un gen es suficiente y el lazo de retroalimentacion positiva no necesita activar a un segundo gen represor, tal y como ocurre en los relojes actuales con dos genes. Esto significa que a nivel genetico un lazo de retroalimentacion negativa no es necesario de forma explicita. Ademas, este modelo no necesita reacciones cooperativas ni la formation de multimeros proteicos, al contrario que en muchos osciladores geneticos. Aplicaciones y futuras lineas de investigacion: En los liltimos anos, se han descubierto muchas moleculas de ARN con capacidad catalitica. El primer modelo de oscilador genetico propuesto en esta tesis usa ribozimas como moleculas repre¬soras. Esto podria proporcionar nuevos principios de diseno en biologia sintetica y una mejor comprension de los relojes celulares regulados por moleculas de ARN. El segundo modelo de oscilador genetico propuesto aqui involucra solo una represion actuando sobre un gen auto-activado y produce oscilaciones robustas. Sorprendente-mente, un segundo gen represor no es necesario al contrario que en los bien conocidos osciladores con dos genes. Este resultado podria ayudar a clarificar los principios de diseno de los relojes celulares naturales y constituir una nueva y eficiente he-rramienta para crear osciladores geneticos sinteticos. Algunas de las futuras lineas de investigation abiertas tras esta tesis son: (1) la validation in vivo e in vitro de ambos modelos, (2) el estudio del potential del segundo modelo como circuito base para la construction de una memoria genetica, (3) el estudio de nuevos osciladores geneticos regulados por ARN no codificante y, por ultimo, (4) el rediseno del se¬gundo modelo de oscilador genetico para su uso como biosensor capaz de detectar genes auto-activados en redes geneticas.

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This paper addresses initial efforts to develop a navigation system for ground vehicles supported by visual feedback from a mini aerial vehicle. A visual-based algorithm computes the ground vehicle pose in the world frame, as well as possible obstacles within the ground vehicle pathway. Relying on that information, a navigation and obstacle avoidance system is used to re-plan the ground vehicle trajectory, ensuring an optimal detour. Finally, some experiments are presented employing a unmanned ground vehicle (UGV) and a low cost mini unmanned aerial vehicle (UAV).

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The optical bistability occurring in laser diode amplifiers is used to design an all-optical logic gate capable to provide the whole set of logic functions. The structure of the reported logic gate is based on two connected 1550nm laser amplifiers (Fabry-Perot and distributed feedback laser amplifiers).

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As we have shown,several output conditions can be obtained from a hybrid optical bistable device when twisted nematic liquid crystal cells are employed as nonlinear elements.

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This work introduces a web-based learning environment to facilitate learning in Project Management. The proposed web-based support system integrates methodological procedures and information systems, allowing to promote learning among geographically-dispersed students. Thus, students who are enrolled in different universities at different locations and attend their own project management courses, share a virtual experience in executing and managing projects. Specific support systems were used or developed to automatically collect information about student activities, making it possible to monitor the progress made on learning and assess learning performance as established in the defined rubric.

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To perceive a coherent environment, incomplete or overlapping visual forms must be integrated into meaningful coherent percepts, a process referred to as ?Gestalt? formation or perceptual completion. Increasing evidence suggests that this process engages oscillatory neuronal activity in a distributed neuronal assembly. A separate line of evidence suggests that Gestalt formation requires top-down feedback from higher order brain regions to early visual cortex. Here we combine magnetoencephalography (MEG) and effective connectivity analysis in the frequency domain to specifically address the effective coupling between sources of oscillatory brain activity during Gestalt formation. We demonstrate that perceptual completion of two-tone ?Mooney? faces induces increased gamma frequency band power (55?71 Hz) in human early visual, fusiform and parietal cortices. Within this distributed neuronal assembly fusiform and parietal gamma oscillators are coupled by forward and backward connectivity during Mooney face perception, indicating reciprocal influences of gamma activity between these higher order visual brain regions. Critically, gamma band oscillations in early visual cortex are modulated by top-down feedback connectivity from both fusiform and parietal cortices. Thus, we provide a mechanistic account of Gestalt perception in which gamma oscillations in feature sensitive and spatial attention-relevant brain regions reciprocally drive one another and convey global stimulus aspects to local processing units at low levels of the sensory hierarchy by top-down feedback. Our data therefore support the notion of inverse hierarchical processing within the visual system underlying awareness of coherent percepts.

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We study dynamics of the bistable logistic map with delayed feedback, under the influence of white Gaussian noise and periodic modulation applied to the variable. This system may serve as a model to describe population dynamics under finite resources in noisy environment with seasonal fluctuations. While a very small amount of noise has no effect on the global structure of the coexisting attractors in phase space, an intermediate noise totally eliminates one of the attractors. Slow periodic modulation enhances the attractor annihilation.

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Root-knot nematodes (RKNs) induce giant cells (GCs) from root vascular cells inside the galls. Accompanying molecular changes as a function of infection time and across different species, and their functional impact, are still poorly understood. Thus, the transcriptomes of tomato galls and laser capture microdissected (LCM) GCs over the course of parasitism were compared with those of Arabidopsis, and functional analysis of a repressed gene was performed. Microarray hybridization with RNA from galls and LCM GCs, infection-reproduction tests and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) transcriptional profiles in susceptible and resistant (Mi-1) lines were performed in tomato. Tomato GC-induced genes include some possibly contributing to the epigenetic control of GC identity. GC-repressed genes are conserved between tomato and Arabidopsis, notably those involved in lignin deposition. However, genes related to the regulation of gene expression diverge, suggesting that diverse transcriptional regulators mediate common responses leading to GC formation in different plant species. TPX1, a cell wall peroxidase specifically involved in lignification, was strongly repressed in GCs/galls, but induced in a nearly isogenic Mi-1 resistant line on nematode infection. TPX1 overexpression in susceptible plants hindered nematode reproduction and GC expansion. Time-course and cross-species comparisons of gall and GC transcriptomes provide novel insights pointing to the relevance of gene repression during RKN establishment.

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Integrated master-oscillator power amplifiers driven under steady-state injection conditions are known to show a complex dynamics resulting in a variety of emission regimes. We present experimental results on the emission characteristics of a 1.5 µm distributed feedback tapered master-oscillator power-amplifier in a wide range of steady-state injection conditions, showing different dynamic behaviors. The study combines the optical and radio-frequency spectra recorded under different levels of injected current into the master oscillator and the power amplifier sections. Under low injection current of the master oscillator the correlation between the optical and radio-frequency spectral maps allows to identify operation regimes in which the device emission arises from either the master oscillator mode or from the compound cavity modes allowed by the residual reflectance of the amplifier front facet. The quasi-periodic occurrence of these emission regimes as a function of the amplifier current is interpreted in terms of a thermally tuned competition between the modes of the master oscillator and the compound cavity modes. Under high injection current of the masteroscillator, two different regimes alternate quasi-periodically as a function of the injected current in the power amplifier: a stable regime with a single mode emission at the master oscillator frequency, and an unstable and complex self-pulsating regime showing strong peaks in the radio-frequency spectra as well as multiple frequencies in the optical spectra.

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Los algoritmos basados en registros de desplazamiento con realimentación (en inglés FSR) se han utilizado como generadores de flujos pseudoaleatorios en aplicaciones con recursos limitados como los sistemas de apertura sin llave. Se considera canal primario a aquel que se utiliza para realizar una transmisión de información. La aparición de los ataques de canal auxiliar (en inglés SCA), que explotan información filtrada inintencionadamente a través de canales laterales como el consumo, las emisiones electromagnéticas o el tiempo empleado, supone una grave amenaza para estas aplicaciones, dado que los dispositivos son accesibles por un atacante. El objetivo de esta tesis es proporcionar un conjunto de protecciones que se puedan aplicar de forma automática y que utilicen recursos ya disponibles, evitando un incremento sustancial en los costes y alargando la vida útil de aplicaciones que puedan estar desplegadas. Explotamos el paralelismo existente en algoritmos FSR, ya que sólo hay 1 bit de diferencia entre estados de rondas consecutivas. Realizamos aportaciones en tres niveles: a nivel de sistema, utilizando un coprocesador reconfigurable, a través del compilador y a nivel de bit, aprovechando los recursos disponibles en el procesador. Proponemos un marco de trabajo que nos permite evaluar implementaciones de un algoritmo incluyendo los efectos introducidos por el compilador considerando que el atacante es experto. En el campo de los ataques, hemos propuesto un nuevo ataque diferencial que se adapta mejor a las condiciones de las implementaciones software de FSR, en las que el consumo entre rondas es muy similar. SORU2 es un co-procesador vectorial reconfigurable propuesto para reducir el consumo energético en aplicaciones con paralelismo y basadas en el uso de bucles. Proponemos el uso de SORU2, además, para ejecutar algoritmos basados en FSR de forma segura. Al ser reconfigurable, no supone un sobrecoste en recursos, ya que no está dedicado en exclusiva al algoritmo de cifrado. Proponemos una configuración que ejecuta múltiples algoritmos de cifrado similares de forma simultánea, con distintas implementaciones y claves. A partir de una implementación sin protecciones, que demostramos que es completamente vulnerable ante SCA, obtenemos una implementación segura a los ataques que hemos realizado. A nivel de compilador, proponemos un mecanismo para evaluar los efectos de las secuencias de optimización del compilador sobre una implementación. El número de posibles secuencias de optimizaciones de compilador es extremadamente alto. El marco de trabajo propuesto incluye un algoritmo para la selección de las secuencias de optimización a considerar. Debido a que las optimizaciones del compilador transforman las implementaciones, se pueden generar automáticamente implementaciones diferentes combinamos para incrementar la seguridad ante SCA. Proponemos 2 mecanismos de aplicación de estas contramedidas, que aumentan la seguridad de la implementación original sin poder considerarse seguras. Finalmente hemos propuesto la ejecución paralela a nivel de bit del algoritmo en un procesador. Utilizamos la forma algebraica normal del algoritmo, que automáticamente se paraleliza. La implementación sobre el algoritmo evaluado mejora en rendimiento y evita que se filtre información por una ejecución dependiente de datos. Sin embargo, es más vulnerable ante ataques diferenciales que la implementación original. Proponemos una modificación del algoritmo para obtener una implementación segura, descartando parcialmente ejecuciones del algoritmo, de forma aleatoria. Esta implementación no introduce una sobrecarga en rendimiento comparada con las implementaciones originales. En definitiva, hemos propuesto varios mecanismos originales a distintos niveles para introducir aleatoridad en implementaciones de algoritmos FSR sin incrementar sustancialmente los recursos necesarios. ABSTRACT Feedback Shift Registers (FSR) have been traditionally used to implement pseudorandom sequence generators. These generators are used in Stream ciphers in systems with tight resource constraints, such as Remote Keyless Entry. When communicating electronic devices, the primary channel is the one used to transmit the information. Side-Channel Attack (SCA) use additional information leaking from the actual implementation, including power consumption, electromagnetic emissions or timing information. Side-Channel Attacks (SCA) are a serious threat to FSR-based applications, as an attacker usually has physical access to the devices. The main objective of this Ph.D. thesis is to provide a set of countermeasures that can be applied automatically using the available resources, avoiding a significant cost overhead and extending the useful life of deployed systems. If possible, we propose to take advantage of the inherent parallelism of FSR-based algorithms, as the state of a FSR differs from previous values only in 1-bit. We have contributed in three different levels: architecture (using a reconfigurable co-processor), using compiler optimizations, and at bit level, making the most of the resources available at the processor. We have developed a framework to evaluate implementations of an algorithm including the effects introduced by the compiler. We consider the presence of an expert attacker with great knowledge on the application and the device. Regarding SCA, we have presented a new differential SCA that performs better than traditional SCA on software FSR-based algorithms, where the leaked values are similar between rounds. SORU2 is a reconfigurable vector co-processor. It has been developed to reduce energy consumption in loop-based applications with parallelism. In addition, we propose its use for secure implementations of FSR-based algorithms. The cost overhead is discarded as the co-processor is not exclusively dedicated to the encryption algorithm. We present a co-processor configuration that executes multiple simultaneous encryptions, using different implementations and keys. From a basic implementation, which is proved to be vulnerable to SCA, we obtain an implementation where the SCA applied were unsuccessful. At compiler level, we use the framework to evaluate the effect of sequences of compiler optimization passes on a software implementation. There are many optimization passes available. The optimization sequences are combinations of the available passes. The amount of sequences is extremely high. The framework includes an algorithm for the selection of interesting sequences that require detailed evaluation. As existing compiler optimizations transform the software implementation, using different optimization sequences we can automatically generate different implementations. We propose to randomly switch between the generated implementations to increase the resistance against SCA.We propose two countermeasures. The results show that, although they increase the resistance against SCA, the resulting implementations are not secure. At bit level, we propose to exploit bit level parallelism of FSR-based implementations using pseudo bitslice implementation in a wireless node processor. The bitslice implementation is automatically obtained from the Algebraic Normal Form of the algorithm. The results show a performance improvement, avoiding timing information leakage, but increasing the vulnerability against differential SCA.We provide a secure version of the algorithm by randomly discarding part of the data obtained. The overhead in performance is negligible when compared to the original implementations. To summarize, we have proposed a set of original countermeasures at different levels that introduce randomness in FSR-based algorithms avoiding a heavy overhead on the resources required.

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In this paper, a fuzzy feedback linearization is used to control nonlinear systems described by Takagi-Suengo (T-S) fuzzy systems. In this work, an optimal controller is designed using the linear quadratic regulator (LQR). The well known weighting parameters approach is applied to optimize local and global approximation and modelling capability of T-S fuzzy model to improve the choice of the performance index and minimize it. The approach used here can be considered as a generalized version of T-S method. Simulation results indicate the potential, simplicity and generality of the estimation method and the robustness of the proposed optimal LQR algorithm.