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En este trabajo se pretende mejorar la calidad de los procesos industriales mediante la clasificación de fallos. Es de vital importancia tener un buen control sobre la calidad en un proceso industrial, dado que un fallo puede provocar la disminución de la calidad del proceso que puede suponer un elevado costes personales, materiales y medioambientales. Debido a la entrada de la industria 4.0 es cada vez más común la monitorización de los procesos industriales la cual acaba resultando en una gran cantidad de datos que pueden aprovecharse para mejorar la calidad del proceso. Con este estudio se analiza el uso de métodos de reducción de la dimensionalidad no lineales, concretamente Locally Linear Embedding (LLE) e ISOMAP, para la clasificación de fallos en plantas. Aplicando diferentes aproximaciones y realizando diferentes experimentos se intentará identificar una serie de fallos pertenecientes a un benchmark, muy utilizado en la literatura científica, de una estación depuradora de aguas residuales (EDAR) llamado BSM2. Además, se realiza un segundo análisis utilizando algoritmos de agrupamiento basados en densidad (DBSCAN, HDBSCAN y OPTICS), con los que se tratará de formar agrupaciones que sean capaces de clasificar los fallos de la EDAR. Por último, puntualizar que la realización de los experimentos ha sido realizada con lenguaje Python, This work aims to improve the quality of industrial processes by classifying failures. It is vitally important to have good quality control in an industrial process, since a failure can cause a decrease in the quality of the process that can lead to high personal, material and environmental costs. Due to the entry of industry 4.0, the monitoring of industrial processes is increasingly common, which ends up resulting in a large amount of data that can be used to improve the quality of the process. This study analyzes the use of non-linear dimensionality reduction methods, specifically Locally Linear Embedding (LLE) and ISOMAP, for the classification of plant failures. Applying different approaches and carrying out different experiments, an attempt will be made to identify a series of failures belonging to a benchmark, widely used in scientific literature, of a wastewater treatment plant (WWTP) called BSM2. In addition, a second analysis is performed using density-based clustering algorithms (DBSCAN, HDBSCAN and OPTICS), with which it will be tried to form clusters that are capable of classifying the failures of the WWTP. Finally, point out that the experiments have been carried out with the Python language., Departamento de Ingeniería de Sistemas y Automática, Máster en Investigación en Ingeniería de Procesos y Sistemas Industriales

El principal objetivo de éste trabajo fin de grado ha sido recopilar una serie de métodos para el análisis de fallos que usan las industrias en la actualidad y analizarlos desde un punto de vista teórico, explicando como se desarrollan e implementan los diferentes métodos en la industria, a modo de guía hemos hecho especial énfasis en los métodos más usados, en el hecho de buscar antecedentes hemos recopilado información histórica de cada uno de los métodos y hemos situado los diferentes avances en la industria en el tiempo. En la actualidad, con el desarrollo de nuevas tecnologías y los avances en lo que viene siendo las 4ª revolución industrial están apareciendo nuevas formas de analizar y predecir fallos , con el uso del big data, sensores, robots… lo que conocemos como la industria 4.0 y en la que me ha gustado enfatizar en este trabajo por su importancia futura en la industria. Por último como todos estos métodos encaminan al control de calidad en una industria, he realizado una breve introducción al término de calidad, ya que me ha parecido de importancia tener apuntes sobre él. The main objective of this final degree project has been to compile a series of methods for the analysis of failures that industries currently use and analyze them from a theoretical point of view, explaining how the different methods are developed and implemented in the industry, as a guide we have placed special emphasis on the most used methods, in the fact of looking for a background we have collected historical information on each of the methods and we have located the different advances in the industry over time. At present, with the development of new technologies and the advances in what has been the 4th industrial revolution, new ways of analyzing and predicting failures are emerging, with the use of big data, sensors, robots ... what we know as industry 4.0 and in which I liked to emphasize this work for its future importance in the industry. Finally, as all these methods are aimed at quality control in an industry, I have made a introduction to the term of quality, since it seemed important to me to have notes on it. Universidad de Sevilla. Ingeniería en Tecnologías Industriales

5-Nitroimidazole (5-NI) compounds are used to treat a variety of bacterial and parasitic infections. Metronidazole (Mz), a 5-NI drug, is a safe and affordable drug that has been used for nearly half a century to treat infections caused by intestinal pathogens. When combined with other medications Mz has successfully been used to treat H. pylori infections. H. pylori is a microaerophilic bacteria that causes a range of gastrointestinal diseases. While Mz is active against H. pylori, the treatment failure rate of Mz centered therapy is increasing (Peter J. Jenks 2002). Others have taken advantage of the ability to synthesize structurally diverse 5-NI compounds and have found that some of the newly derived compounds are highly potent compared to Mz (Jacqueline A. Upcroft 2006). We asked if 5-Ni compounds, apart from Mz, could reduce the growth rate of H. pylori and potentially function as new antibiotics. We show that 5-NI compounds are active against multiple strains of H. pylori. Also, we found four compounds that are able to overcome Mz-resistance. Finally, we propose a new method for gaining a better understating of Mz resistance mechanisms using a strain's compound activity profile coupled with phylogenetic tools

The objective in the present work was to evaluate the genetic diversity among 15 indigenous populations of camu-camu plants, identifying important characteristics in the evaluation of genetic divergence, based on the initial characteristics of the seedlings. Seeds extracted from fruits deriving from fifteen indigenous populations of camu-camu were collected. The experimental design was entirely random, with fifteen treatments (populations), and fifteen repetitions (each sub-sample), considering 30 seeds per subsample as an experimental unit. At 40 days after sowing the following were evaluated: the percentage of emergence, the index of emergence velocity, the average time of germination, the height of the seedling and the number of leaves. The data obtained was submitted to variance analysis, and the averages were grouped by the Scott and Knott (1974) test. The genetic diversity was studied according to the Tocher grouping method, based on the Mahalanobis distance (D2ii) and canonical variables. The fifteen populations are divergent among themselves and the Rio Branco Estirão do Veado, Rio Branco Onofre and Igarapé Agua Boa populations are indicated to have hybridization with other populations due to the high divergence, as well as the rates of emergence and vigor of the seedlings. The height of the seedlings, percentage and speed of emergence, are those that most indicate genetic divergence. The measuring techniques of genetic divergence, canonical variables Mahalanobis distances are useful and corroborating in the evaluation of genetic divergence of the camu-camu plant.

El psicoestimulante sintético “éxtasis” (±3,4-metilendioximetanfetamina, MDMA) es la tercera droga de abuso más consumida en el mundo. La MDMA actúa como agonista indirecto de la serotonina y dopamina al invertir la acción de los transportadores de serotonina (5-HTT) y dopamina, e inhibe el citocromo P450 2D6 (CYP2D6) de forma casi-irreversible. Se ha sugerido que las mujeres son más sensibles que los hombres a los efectos subjetivos de la MDMA, principalmente los negativos. Sin embargo, no hay estudios clínicos experimentales que hayan evaluado satisfactoriamente los posibles factores contribuyentes a dicha observación, entre los cuales se hallan las hormonas sexuales. Tampoco se ha evaluado la influencia de algunos polimorfismos genéticos de las enzimas que intervienen en su farmacocinética (CYP2D6; catecol-O-metiltransferasa, COMT),o en sus efectos farmacológicos (5-HTT; COMT). El objetivo de la presente memoria es examinar el impacto del género, la genética y la interacción género-genética en la farmacología clínica de la MDMA. Un total de 27 consumidores recreacionales de éxtasis sanos fueron incluidos (12 mujeres). Todos fueron fenotipados como metabolizadores rápidos del CYP2D6 mediante el dextrometorfano como prueba de actividad metabólica. Se genotipó a los sujetos y se les separó en 2 grupos respecto al CYP2D6 (como portador de 1 o 2 alelos funcionantes), COMT Val158Met (portador de alelos val/val o met/*) y la región polimorfica ligada al 5-HTT (5-HTTLPR) (portador de alelos l/* o s/s). Se administró una dosis oral de MDMA ajustada al peso (1.4 mg/kg, rango 75-100 mg) similar a las dosis recreacionales. En las mujeres, se controló la posible influencia de las hormonas sexuales (anticonceptivos orales y la fase del ciclo menstrual). El estudio clínico de Fase I evaluó tres factores importantes en diferentes puntos temporales durante 25 horas. En primer lugar, los parámetros farmacocinéticos de la MDMA y sus metabolitos HMMA, MDA, HMA. En segundo lugar, los efectos fisiológicos de la MDMA (presión arterial sistólica y diastólica, frecuencia cardiaca, temperatura oral, diámetro pupilar, tensión de la musculatura extraocular). Y por último, los efectos subjetivos positivos y negativos de la MDMA mediante Escalas Analógicas Visuales y dos cuestionarios, el ARCI (Addiction Research Inventory Center) y el VESSPA (Valoración de los Efectos Subjetivos en Sustancias con Potencial de Abuso). Adicionalmente se evaluaron las concentraciones de dos sustratos (dextrometorfano y cafeína) para evaluar las posibles interacciones metabólicas de la MDMA en los citocromos CYP2D6, CY3A4 y CYP1A2. Los principales hallazgos farmacocinéticos muestran que los sujetos alcanzaron concentraciones plasmáticas de MDMA y MDA similares independientemente del género y el genotipo CYP2D6 o COMT Val158Met. Sin embargo, los portadores del genotipo CYP2D6 con mayor actividad (2 alelos funcionantes) presentaron mayores concentraciones plasmáticas de HMMA. Los hombres presentaron una mayor depuración hepática de MDMA que las mujeres. En relación a los efectos inducidos por la MDMA, las mujeres experimentaron efectos adversos más intensos que los hombres a nivel cardiovascular, en la temperatura corporal, mareo, sedación y síntomas depresivos o de tristeza, pero no se observaron diferencias de género en los efectos subjetivos positivos. De forma general, los sujetos con actividad elevada de la COMT Val158Met (val/val) o 5-HTTLPR (l/*) presentaron más efectos cardiovasculares y aquellos con una funcionalidad disminuida (met/* o s/s, respectivamente) mostraron mayores efectos subjetivos negativos (mareo, ansiedad y sedación), y no se observaron diferencias en los efectos subjetivos positivos en cada genotipo. Pero evaluando el genotipo de forma conjunta con el género, las mujeres experimentaron más efecto en la frecuencia cardiaca en los subgrupos de cada genotipo (COMT Val158Met o 5-HTTLPR). En el subgrupo COMT-met/*, las mujeres presentaron más mareo, sedación y ansiedad. En el subgrupo 5-HTLPR-l/* las mujeres mostraron más presión arterial sistólica, somnolencia y sedación, mientras que los hombres presentaron mayor aumento del diámetro pupilar. En el subgrupo 5-HTTLPR-s/s, las mujeres experimentaron mayor aumento de la temperatura oral y del mareo. La MDMA produjo una inhibición muy relevante del citocromo CYP2D6, menos importante del CYP3A4 e indujo levemente la actividad del CYP1A2. En todos los casos la inhibición-inducción fur mayor en mujeres que en hombres. En conclusión, existen diferencias de género marcadas en la farmacología de la MDMA. Las mujeres experimentan con mayor intensidad que los hombres algunos efectos fisiológicos y subjetivos negativos. Esta observación no parece estar relacionada con la farmacocinética de la MDMA. En cambio, los polimorfismos del 5-HTTLPR y/o COMT Val158Met juegan un papel importante en modular el riesgo de los efectos adversos de la MDMA, principalmente los cardiovasculares., The synthetic psychostimulant “ecstasy” (±3,4-methylenedioxymethamphetamine, MDMA) is the third drug of abuse most consumed worldwide. It acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive than men to MDMA subjective effects, mainly negative ones, but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. Furthermore, there are no studies evaluating the influence of some genetic polymorphism of the enzymes implicated in the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and the pharmacological effects (serotonin transporter, 5-HTT; COMT) of MDMA. The present memory will examine the impact of gender, genetics and gender-genotype interaction on the clinical pharmacology of MDMA. A total of 27 (12 women) healthy recreational users of ecstasy were included. All of them were phenotyped as extensive metabolizers for CYP2D6 with dextromethorphan probe drug. Subjects were genotyped and classified in CYP2D6 (as carrier of 1 or two functional alleles), COMT Val158Met (as val/val or met/* carrier) and 5-HTTLPR (as l/* or s/s carrier). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75-100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and they performed the experimental session during the early follicular phase of their menstrual cycle. The Fase I clinical study evaluated three important factors in several time-points during 25 hours. Firstable, the pharmacokinetics of MDMA and its metabolites HMMA, MDA and HMA. Secondly, the physiological effects of MDMA (systolic and diastolic blood pressure, heart rate, oral temperature, pupil diameter, and extraocular muscle tension). And at last, the positive and negative subjective effects of MDMA with Visual Analog Scales, and the following two questionnaires: ARCI (Addiction Research Center Inventory), and VESSPA (Subjective Effects Valuated in Substances with Potential of Addiction). It was considered gender and/or genetic polymorphisms of CYP2D6, COMT Val158Met, and 5-HTTLPR (5-HTT gene linked to polymorphic region) for those purposes. In addition, we determined the concentrations of two metabolic substrates (detromethorphan and caffeine) to evaluate the possible metabolic interactions of MDMA on cytochromes CYP2D6, CY3A4 y CYP1A2. The principal pharmacokinetic findings show that all of 27 volunteers reached similar MDMA and MDA plasma concentrations irrespective of gender. Men showed a higher hepatic clearance of MDMA than women. However, higher HMMA plasma concentrations were determined in carriers with high functionality of CYP2D6 genotype (two functional alleles). According MDMA-induced effects, female subjects displayed more intense physiological (systolic blood pressure, heart rate, and oral temperature) and negative effects (dizziness, sedation, and depressive symptoms) than men. No gender differences were observed in positive subjective effects. Genotypes of COMT Val158Met or 5-HTTLPR with high functionality (val/val or l/* respectively) determined greater cardiovascular effects (systolic and diastolic blood pressure and heart rate), and those genotypes with low functionality (met/* or s/s respectively) showed negative subjective effects (dizziness, anxiety, and sedation). Subjects experienced similar positive effects irrespective of genotype. The gender-genotype interaction showed gender differences in all subgroups. Women experienced more heart rate increase than men irrespective of subgroup of genotypes. In COMT-met/* subgroup females show more dizziness, sedation and anxiety; in 5-HTTLPR-l/* subgroup females experienced more systolic blood pressure, drowsiness and sedation, meanwhile men showed more pupil diameter. In 5-HTTLPR-s/s subgroup, females experienced more increase in oral temperature and dizziness. MDMA induced a very important inhibition of CYP2D6 activity and in a lesser degree of CYP3A4. The activity of CYP1A2 was slightly increased. In all cases the inhibition-induction were higher in females in comparison to males. In conclusion, there are marked gender differences in MDMA pharmacology. Women experience greater heightened physiological and negative subjective effects than men. This observation does not appear to be related to drug disposition. In contrast, the 5-HTTLPR and/or COMT val158met polymorphisms combine to play an important role in modulating risk for MDMA adverse effects, mainly cardiovascular ones.

La presente tesis doctoral se ha centrado en el estudio de la educación no formal como parte imprescindible en la formación de las personas. La actividad física y el deporte actúan como mediadores educativos y son potentes motivadores e impulsores del conocimiento.La estrategia de educación integral MARACAS para niños y jóvenes de 5 a 15 años resultado del estudio longitudinal (2009, 2010 y 2011) favorece la transformación social a través de la actividad física. La implementación en un contexto paraescolar, proporciona habilidades competenciales en los participantes, los cuales desarrollan mecanismos necesarios para coadyuvar de manera exitosa en la completa formación del ser humano desde la perspectiva de las inteligencias múltiples. El presente estudio contempló herramientas de corte cualitativo y cuantitativo en cada una de sus fases, lo que permitió obtener resultados objetivos que contribuyan en la formación completa de la juventud y por ende en la transformación social de Ciudad Juárez en México. Lo cual nos mantiene comprometidos con la verdad, con la ética, la responsabilidad personal y social de tan maravillosa ciencia. Los resultados más significativos, entre otros, determinan el avance de los participantes desde dos parámetros. El primero, a partir de un progreso significativo en las habilidades competenciales, y el segundo, desde una valoración progresiva y reveladora de las inteligencias múltiples, tomando como eje central los escenarios de aprendizaje en donde el alumno desarrolla de manera vivencial una forma alternativa de manifestar sus talentos y expresarlos en escenarios reales. Igualmente los resultados nos indican que entre más tiempo pasaban los participantes en el proyecto, mayor era su progreso en las habilidades competenciales y las inteligencias múltiples. El planteamiento de la estrategia del proyecto MARACAS como instrumento de educación integral favorece el aprendizaje desde la actividad física y el deporte, además ofrece un enfoque complementario para fortalecer las capacidades más destacadas de los participantes, descubriendo nuevos talentos y reparando las debilidades.

We study some of the consequences of the SU(6)$_{L}\otimes$U(1)$_{Y}$ model of unification of electroweak interactions and families with a horizontal gauge group SU(2)$_{H}$, paying special attention to processes with flavor changing neutral currents. We compute at tree level the decays $K^{+}\longrightarrow \pi^{+}\mu^{+}e^{-}$, $K_L^0\longrightarrow \mu^{+}e^{-}$ and $\mu^{-} \longrightarrow e^{-} \bar{\nu_e} \nu_\mu$ from which we obtain lower bounds for the mass of the horizontal gauge boson associated with FCNC. Finally we obtain limits on the mixing between ordinary and exotic charged leptons.

Hybrid Brain-Computer Interfaces (BCI) are representing a recent approach to develop practical BCIs. In such a system disabled users are able to use all their remaining functionalities as control possibilities in parallel with the BCI. Sometimes these people have residual activity of their muscles. Therefore, in the presented hybrid BCI framework we want to explore the parallel usage of electroencephalographic (EEG) and electromyographic (EMG) activity, whereby the control abilities of both channels are fused. Results showed that the participants could achieve a good control of their hybrid BCI independently of their level of muscular fatigue. Thereby the multimodal fusion approach of muscular and brain activity yielded better and more stable performance compared to the single conditions. Even in the case of an increasing muscular fatigue a good control (moderate and graceful degradation of the performance compared to the non-fatigued case) and a smooth handover could be achieved. Therefore, such systems allow the users a very reliable hybrid BCI control although they are getting more and more exhausted or fatigued during the day.

Inverse solution allows to estimate sources that generate a given scalp EEG topography. Recently, it has been used in Brain Computer Interfaces (BCIs) to extract robust features based on the hypothesis that projection onto the source space (high dimensional space) yield promising improvement in classification performance over surface EEG through offline experiments. However, these inverse methods are optimized for localizing the intracranial sources of the EEG signals. Therefore, using inverse solution in its current form may not be optimal for classification purposes and its online application is yet to be proven. To this end, this thesis aims at characterizing different parameters associated with inverse solution such that it results in increased classification performance when applied online with respect to surface EEG while maintaining its source localization capabilities. This thesis documents three major contributions : (i) it presents methods for feature selection and classification using inverse solution and surface EEG for Event Related Potential (ERP) based BCIs, (ii) it reports on the optimal choice of parameters for inverse solution to balance between localization and classification for BCI using the developed feature selection and classification methods, (iii) it applies this procedure on four BCI experiments and shows that it improves classification performance over surface EEG in online conditions. First, we focus on developing feature selection and classification methods that are capable to run for online ERP-based BCIs. The use of inverse solution results in an increase in the available number of features. To select features, we apply Fisher score to quantify the discriminability of each source and select the same number of top-most discriminant sources at each time instance in a selected time window. To classify, an ensembled approach was followed where we made individual classifier for each feature and combined them using Naïve Bayes rule to obtain the resultant decision. This procedure prevents overfitting and requires only the number of sources to be optimized. For comparison with surface EEG, we applied Fisher Linear Discriminant (FLD) spatial filters at each time instance on the potential from all the EEG channels. Individual classifiers are trained on each FLD projection and are combined using the same rule. This comparison is extended with two additional classifiers for surface EEG: multiple projection FLD and specific channel classifier. Second, the parameters of the inverse solution are characterized in terms of their localization and classification capabilities for ERP based BCI. The parameters include forward head model, regularization constraint and regularization parameter. We find that, the choice of head model does not affect the optimum classification performance (although, it clearly affects the localization process) that can be achieved with our feature selection and classification methods. For a chosen forward model, the values of the regularization parameter that yield optimum classification performance remain consistent across subjects and experiments. The range however depends on regularization constraint. Furthermore, we find that the same range results in minimum localization error for different noise levels in EEG. Regarding standardized regularization constraint, although they can achieve lower localization error, they also have lower classification performance. Finally, the proposed feature selection and classification methods are applied on four different ERP experiments. The first three experiments: ErrP, RSVP and P300-speller were performed offline and were used to characterize the number of features for inverse solution that exhibit optimum classification performance. We found that the classification performance with a small number of features was higher compared to surface EEG and overall is less sensitive to the number of features. The results for classification performance using inverse solution are in-line with the literature on ERP based BCI. Following the analysis on offline experiments, we showed the feasibility of using inverse solution to online ErrP experiment. In summary, this thesis provides an insight on the use of estimated intracranial sources as features for online BCI applications. Specifically, it characterizes parameter choice along with feature selection and classification methods. This results in high classification performance while retaining low localization error. Overall, the methods developed are easily applicable to ERP based BCIs as demonstrated in both offline and online experiments.