<p> <p>&nbsp / </p> </p> <p align="left">This study utilized large-scale gene expression data to define the regulatory networks of genes expressing in the hippocampus to which multiple disease pathologies may be associated. Specific aims were: ident i fy key regulatory transcription factors (TFs) responsible for observed gene expression patterns, reconstruct transcription regulatory networks, and prioritize likely TFs responsible for anatomically restricted gene expression. Most of the analysis was restricted to the CA3 sub-region of Ammon&rsquo / s horn within the hippocampus. We identified 155 core genes expressing throughout the CA3 sub-region and predicted corresponding TF binding site (TFBS) distributions. Our analysis shows plausible transcription regulatory networks for twelve clusters of co-expressed genes. We demonstrate the validity of the predictions by re-clustering genes based on TFBS distributions and found that genes tend to be correctly assigned to groups of previously identified co-expressing genes with sensitivity of 67.74% and positive predictive value of 100%. Taken together, this study represents one of the first to merge anatomical architecture, expression profiles and transcription regulatory potential on such a large scale in hippocampal sub-anatomy.</p>

This thesis deals with enhancing the performance of Fuzzy Logic (FL) based PI controllers for High Voltage Direct Current Transmission Systems (HVDC) by optimizing the key parameters i.e. membership functions (MFs) and fuzzy rule base in the controllers design. In the first part of the thesis, an adaptive Fuzzy PI controller is designed and the effect of various MF shapes, widths and distribution on the performance of a FL controlled HVDC system under different system conditions is studied with the aim of selecting a MF which minimizes the total control error. Simulated results show that the shape, width and distribution of a MF influences the performance of the FL controller and concludes that nonlinear MFs (i.e. Gaussian) offer a more better choice than linear (i.e. Triangular) MFs as the former provides a smoother transition at the switching points and thus propose a better controller. In the second part of the thesis, a Neuro-Fuzzy (NF) controller to update the fuzzy rule base with changing system conditions is proposed, which in turn adjusts the PI gains of a conventional PI controller. Results from simulations illustrate the potential of the proposed control scheme as the NF controller successfully adapts to different system conditions and is able to minimize the total current error. / UOIT

There are many situations where a linguistic description of complex phenomena allows better assessments. It is well known that the assessment of water quality continues depending heavily upon subjective judgments and interpretation, despite the huge datasets available nowadays. In that sense, the aim of this study has been to introduce intelligent linguistic operations to analyze databases, and produce self interpretable water quality indicators, which tolerate both imprecision and linguistic uncertainty. Such imprecision typically reflects the ambiguity of human thinking when perceptions need to be expressed. Environmental management concepts such as: "water quality", "level of risk", or "ecological status" are ideally dealt with linguistic variables. In the present Thesis, the flexibility of computing with words offered by fuzzy logic has been considered in these management issues. Firstly, a multipurpose hierarchical water quality index has been designed with fuzzy reasoning. It integrates a wide set of indicators including: organic pollution, nutrients, pathogens, physicochemical macro-variables, and priority micro-contaminants. Likewise, the relative importance of the water quality indicators has been dealt with the analytic hierarchy process, a decision-aiding method. Secondly, a methodology based on a hybrid approach that combines fuzzy inference systems and artificial neural networks has been used to classify ecological status in surface waters according to the Water Framework Directive. This methodology has allowed dealing efficiently with the non-linearity and subjective nature of variables involved in this classification problem. The complexity of inference systems, the appropriate choice of linguistic rules, and the influence of the functions that transform numerical variables into linguistic variables have been studied. Thirdly, a concurrent neuro-fuzzy model based on screening ecological risk assessment has been developed. It has considered the presence of hazardous substances in rivers, and incorporates an innovative ranking and scoring system, based on a self-organizing map, to account for the likely ecological hazards posed by the presence of chemical substances in freshwater ecosystems. Hazard factors are combined with environmental concentrations within fuzzy inference systems to compute ecological risk potentials under linguistic uncertainty. The estimation of ecological risk potentials allows identifying those substances requiring stricter controls and further rigorous risk assessment. Likewise, the aggregation of ecological risk potentials, by means of empirical cumulative distribution functions, has allowed estimating changes in water quality over time. The neuro-fuzzy approach has been validated by comparison with biological monitoring. Finally, a hierarchical fuzzy inference system to deal with sediment based ecological risk assessment has been designed. The study was centered in sediments, since they produce complementary findings to water quality analysis, especially when temporal trends are required. Results from chemical and eco-toxicological analyses have been used as inputs to two parallel inference systems which assess levels of contamination and toxicity, respectively. Results from both inference engines are then treated in a third inference engine which provides a final risk characterization, where the risk is provided in linguistic terms, with their respective degrees of certitude. Inputs to the risk system have been the levels of potentially toxic substances, mainly metals and chlorinated organic compounds, and the toxicity measured with a screening test which uses the photo-luminescent bacteria Vibrio fischeri. The Ebro river basin has been selected as case study, although the methodologies here explained can easily be applied to other rivers. In conclusion, this study has broadly demonstrated that the design of water quality indexes, based on fuzzy logic, emerges as suitable and alternative tool to support decision makers involved in effective sustainable river basin management plans. / Existen diversas situaciones en las cuales la descripción en términos lingüísticos de fenómenos complejos permite mejores resultados. A pesar de los volúmenes de información cuantitativa que se manejan actualmente, es bien sabido que la gestión de la calidad del agua todavía obedece a juicios subjetivos y de interpretación de los expertos. Por tanto, el reto en este trabajo ha sido la introducción de operaciones lógicas que computen con palabras durante el análisis de los datos, para la elaboración de indicadores auto-interpretables de calidad del agua, que toleren la imprecisión e incertidumbre lingüística. Esta imprecisión típicamente refleja la ambigüedad del pensamiento humano para expresar percepciones. De allí que las variables lingüísticas se presenten como muy atractivas para el manejo de conceptos de la gestión medioambiental, como es el caso de la "calidad del agua", el "nivel de riesgo" o el "estado ecológico". Por tanto, en la presente Tesis, la flexibilidad de la lógica difusa para computar con palabras se ha adaptado a diversos tópicos en la gestión de la calidad del agua. Primero, se desarrolló un índice jerárquico multipropósito de calidad del agua que se obtuvo mediante razonamiento difuso. El índice integra un extenso grupo de indicadores que incluyen: contaminación orgánica, nutrientes, patógenos, variables macroscópicas, así como sustancias prioritarias micro-contaminantes. La importancia relativa de los indicadores al interior del sistema de inferencia se estimó con un método de análisis de decisiones, llamado proceso jerárquico analítico. En una segunda fase, se utilizó una metodología híbrida que combina los sistemas de inferencia difusos y las redes neuronales artificiales, conocida como neuro-fuzzy, para el estudio de la clasificación del estado ecológico de los ríos, de acuerdo con los lineamientos de la Directiva Marco de Aguas. Esta metodología permitió un manejo adecuado de la no-linealidad y naturaleza subjetiva de las variables involucradas en este problema clasificatorio. Con ella, se estudió la complejidad de los sistemas de inferencia, la selección apropiada de reglas lingüísticas y la influencia de las funciones que transforman las variables numéricas en lingüísticas. En una tercera fase, se desarrolló un modelo conceptual neuro-fuzzy concurrente basado en la metodología de evaluación de riesgo ecológico preliminar. Este modelo consideró la presencia de sustancias peligrosas en los ríos, e incorporó un mapa auto-organizativo para clasificar las sustancias químicas, en términos de su peligrosidad hacia los ecosistemas acuáticos. Con este modelo se estimaron potenciales de riesgo ecológico por combinación de factores de peligrosidad y de concentraciones de las sustancias químicas en el agua. Debido a la alta imprecisión e incertidumbre lingüística, estos potenciales se obtuvieron mediante sistemas de inferencia difusos, y se integraron por medio de distribuciones empíricas acumuladas, con las cuales se pueden analizar cambios espacio-temporales en la calidad del agua. Finalmente, se diseñó un sistema jerárquico de inferencia difuso para la evaluación del riesgo ecológico en sedimentos de ribera. Este sistema estima los grados de contaminación, toxicidad y riesgo en los sedimentos en términos lingüísticos, con sus respectivos niveles de certeza. El sistema se alimenta con información proveniente de análisis químicos, que detectan la presencia de sustancias micro-contaminantes, y de ensayos eco-toxicológicos tipo "screening" que usan la bacteria Vibrio fischeri. Como caso de estudio se seleccionó la cuenca del río Ebro, aunque las metodologías aquí desarrolladas pueden aplicarse fácilmente a otros ríos. En conclusión, este trabajo demuestra ampliamente que el diseño y aplicación de indicadores de calidad de las aguas, basados en la metodología de la lógica difusa, constituyen una herramienta sencilla y útil para los tomadores de decisiones encargados de la gestión sostenible de las cuencas hidrográficas.

This thesis develops approximate dynamic programming (ADP) strategies suitable for process control problems aimed at overcoming the limitations of MPC, which are the potentially exorbitant on-line computational requirement and the inability to consider the future interplay between uncertainty and estimation in the optimal control calculation. The suggested approach solves the DP only for the state points visited by closed-loop simulations with judiciously chosen control policies. The approach helps us combat a well-known problem of the traditional DP called 'curse-of-dimensionality,' while it allows the user to derive an improved control policy from the initial ones. The critical issue of the suggested method is a proper choice and design of function approximator. A local averager with a penalty term is proposed to guarantee a stably learned control policy as well as acceptable on-line performance. The thesis also demonstrates versatility of the proposed ADP strategy with difficult process control problems. First, a stochastic adaptive control problem is presented. In this application an ADP-based control policy shows an "active" probing property to reduce uncertainties, leading to a better control performance. The second example is a dual-mode controller, which is a supervisory scheme that actively prevents the progression of abnormal situations under a local controller at their onset. Finally, two ADP strategies for controlling nonlinear processes based on input-output data are suggested. They are model-based and model-free approaches, and have the advantage of conveniently incorporating the knowledge of identification data distribution into the control calculation with performance improvement.

We propose a novel approach for segmentation of human objects, including face and body, in image sequences. In modern video coding techniques, e.g., MPEG-4 and MPEG-7, human objects are usually the main focus for multimedia applications. We combine temporal and spatial information and employ a neuro-fuzzy mechanism to extract human objects. A fuzzy self-clustering technique is used to divide the video frame into a set of segments. The existence of a face within a candidate face region is ensured by searching for possible constellations of eye-mouth triangles and verifying each eye-mouth combination with the predefined template. Then rough foreground and background are formed based on a combination of multiple criteria. Finally, human objects in the base frame and the remaining frames of the video stream are precisely located by a fuzzy neural network which is trained by a SVD-based hybrid learning algorithm. Through experiments, we compare our system with two other approaches, and the results have shown that our system can detect face locations and extract human objects more accurately.

We develop a neuro-fuzzy network technique to extract TSK-type fuzzy rules from a given set of input-output data for classification problems. Fuzzy clusters are generated incrementally from the training data set, and similar clusters are merged dynamically together through input-similarity, output-similarity, and output-variance tests. The associated membership functions are defined with statistical means and deviations. Each cluster corresponds to a fuzzy IF-THEN rule, and the obtained rules can be further refined by a fuzzy neural network with a hybrid learning algorithm which combines a recursive SVD-based least squares estimator and the gradient descent method. The proposed technique has several advantages. The information about input and output data subspaces is considered simultaneously for cluster generation and merging. Membership functions match closely with and describe properly the real distribution of the training data points. Redundant clusters are combined and the sensitivity to the input order of training data is reduced. Besides, generation of the whole set of clusters from the scratch can be avoided when new training data are considered.

Die zuverlässige Einhaltung von Lieferzusagen stellt ein wichtiges Kriterium bei der Auswahl der Teilnehmer eines auftragsbezogenen Produktionsnetzes dar. Für die objektive Bewertung der Lieferzuverlässigkeit der potenziellen Netzwerkteilnehmer bedarf es der Quantifizierung der relevanten Unsicherheiten integriert in einen allgemein gültigen Ansatz der Verfügbarkeitsprüfung. Die Arbeit stellt daraus resultierend Ansätze zur Berechnung der Unsicherheit vor. Durch die Quantifizierung der Unsicherheit innerhalb der Unternehmen ergibt sich zudem die Möglichkeit der flexiblen, situationsabhängigen Nutzung des für langfristige Rahmenverträge reservierten Sicherheitsbestandes zur Befriedigung kurzfristiger Anfragen. Diese Aufgabe unterstützt ein konfigurierbares Modell zur Entscheidungsunterstützung, das auf einem Neuro-Fuzzy-System basiert. Die Kennzahlen der Lieferzuverlässigkeit unterliegen einem dynamischen Verhalten während des Wertschöpfungsprozesses in dem auftragsbasierten Produktionsnetz. Durch die Integration dieser Kennzahlen in das Management dieses Prozesses ergibt sich die Möglichkeit, aus der Zunahme der Unsicherheit mögliche Störungen und deren Auswirkungen bereits vor ihrem Eintreten zu erfassen und im Rahmen eines präventiven Störungsmanagements zu agieren.

Thesis--Auburn University, 2009. / Abstract. Vita. Includes MatLab code. Includes bibliography (p.43-44).

Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum of neurons, may play a role in this action. Here, we demonstrate that the orexigenic action of ghrelin is totally blunted in CPT1C knockout (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0 ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated the orexigenic action of ghrelin and normalized the levels of AgRP and NPY, as well as their key transcription factors phosphorylated cAMP-response element-binding protein and forkhead box O1. Furthermore, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Third, we demonstrate that ceramides act increasing the BSX expression, the transcription factor that works coordinately with pCREB and FoxO1 to increase orexigenic neuropeptides. Finally we link CPT1C and longevity as we have seen that CPT1CKO mice have reduced lifespan. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism

<p> <p>&nbsp / </p> </p> <p align="left">This study utilized large-scale gene expression data to define the regulatory networks of genes expressing in the hippocampus to which multiple disease pathologies may be associated. Specific aims were: ident i fy key regulatory transcription factors (TFs) responsible for observed gene expression patterns, reconstruct transcription regulatory networks, and prioritize likely TFs responsible for anatomically restricted gene expression. Most of the analysis was restricted to the CA3 sub-region of Ammon&rsquo / s horn within the hippocampus. We identified 155 core genes expressing throughout the CA3 sub-region and predicted corresponding TF binding site (TFBS) distributions. Our analysis shows plausible transcription regulatory networks for twelve clusters of co-expressed genes. We demonstrate the validity of the predictions by re-clustering genes based on TFBS distributions and found that genes tend to be correctly assigned to groups of previously identified co-expressing genes with sensitivity of 67.74% and positive predictive value of 100%. Taken together, this study represents one of the first to merge anatomical architecture, expression profiles and transcription regulatory potential on such a large scale in hippocampal sub-anatomy.</p>