18,021 research outputs found

    Assessing performance of artificial neural networks and re-sampling techniques for healthcare datasets.

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    Re-sampling methods to solve class imbalance problems have shown to improve classification accuracy by mitigating the bias introduced by differences in class size. However, it is possible that a model which uses a specific re-sampling technique prior to Artificial neural networks (ANN) training may not be suitable for aid in classifying varied datasets from the healthcare industry. Five healthcare-related datasets were used across three re-sampling conditions: under-sampling, over-sampling and combi-sampling. Within each condition, different algorithmic approaches were applied to the dataset and the results were statistically analysed for a significant difference in ANN performance. The combi-sampling condition showed that four out of the five datasets did not show significant consistency for the optimal re-sampling technique between the f1-score and Area Under the Receiver Operating Characteristic Curve performance evaluation methods. Contrarily, the over-sampling and under-sampling condition showed all five datasets put forward the same optimal algorithmic approach across performance evaluation methods. Furthermore, the optimal combi-sampling technique (under-, over-sampling and convergence point), were found to be consistent across evaluation measures in only two of the five datasets. This study exemplifies how discrete ANN performances on datasets from the same industry can occur in two ways: how the same re-sampling technique can generate varying ANN performance on different datasets, and how different re-sampling techniques can generate varying ANN performance on the same dataset

    Machine learning based adaptive soft sensor for flash point inference in a refinery realtime process

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    In industrial control processes, certain characteristics are sometimes difficult to measure by a physical sensor due to technical and/or economic limitations. This fact is especially true in the petrochemical industry. Some of those quantities are especially crucial for operators and process safety. This is the case for the automotive diesel Flash Point Temperature (FT). Traditional methods for FT estimation are based on the study of the empirical inference between flammability properties and the denoted target magnitude. The necessary measures are taken indirectly by samples from the process and analyzing them in the laboratory, this process implies time (can take hours from collection to flash temperature measurement) and thus make it very difficult for real-time monitorization, which in fact results in security and economical losses. This study defines a procedure based on Machine Learning modules that demonstrate the power of real-time monitorization over real data from an important international refinery. As input, easily measured values provided in real-time, such as temperature, pressure, and hydraulic flow are used and a benchmark of different regressive algorithms for FT estimation is presented. The study highlights the importance of sequencing preprocessing techniques for the correct inference of values. The implementation of adaptive learning strategies achieves considerable economic benefits in the productization of this soft sensor. The validity of the method is tested in the reality of a refinery. In addition, real-world industrial data sets tend to be unstable and volatile, and the data is often affected by noise, outliers, irrelevant or unnecessary features, and missing data. This contribution demonstrates with the inclusion of a new concept, called an adaptive soft sensor, the importance of the dynamic adaptation of the conformed schemes based on Machine Learning through their combination with feature selection, dimensional reduction, and signal processing techniques. The economic benefits of applying this soft sensor in the refinery's production plant and presented as potential semi-annual savings.This work has received funding support from the SPRI-Basque Gov- ernment through the ELKARTEK program (OILTWIN project, ref. KK- 2020/00052)

    Enhancing Parkinson’s Disease Prediction Using Machine Learning and Feature Selection Methods

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    Several millions of people suffer from Parkinson’s disease globally. Parkinson’s affects about 1% of people over 60 and its symptoms increase with age. The voice may be affected and patients experience abnormalities in speech that might not be noticed by listeners, but which could be analyzed using recorded speech signals. With the huge advancements of technology, the medical data has increased dramatically, and therefore, there is a need to apply data mining and machine learning methods to extract new knowledge from this data. Several classification methods were used to analyze medical data sets and diagnostic problems, such as Parkinson’s Disease (PD). In addition, to improve the performance of classification, feature selection methods have been extensively used in many fields. This paper aims to propose a comprehensive approach to enhance the prediction of PD using several machine learning methods with different feature selection methods such as filter-based and wrapper-based. The dataset includes 240 recodes with 46 acoustic features extracted from 3 voice recording replications for 80 patients. The experimental results showed improvements when wrapper-based features selection method was used with KNN classifier with accuracy of 88.33%. The best obtained results were compared with other studies and it was found that this study provides comparable and superior results

    Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole

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    Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock séptico

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    La sepsis es una afección potencialmente mortal causada por una respuesta anormal del huésped a una infección, produciendo respuestas fisiológicas alteradas que dañan los propios tejidos del paciente y pueden provocar disfunción orgánica e incluso la muerte. Asimismo, algunos pacientes sépticos progresan a shock séptico, caracterizado por alteraciones circulatorias, celulares y metabólicas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunológico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresión, la alta complejidad de la fisiopatología de la sepsis requiere una mayor investigación para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citotóxicos en la sepsis, ya que actúan como patrones moleculares asociados a daño, que inducen estrés oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activación de la piroptosis, un mecanismo de muerte celular programada que produce inflamación mediante la expresión de IL-18, IL-1β and IL-1α. Sin embargo, a pesar de la evidencia de activación del inflamasoma en las células inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activación del inflamasoma NLRP3 y la piroptosis en las células endoteliales, contribuyendo a la disfunción endotelial y la desregulación de la respuesta inmune mediada por el endotelio. Asimismo, también demostramos cómo la acetilación de histonas disminuye la activación de la piroptosis. Además, demostramos que la piroptosis se produce en pacientes con shock séptico y los niveles de histonas circulantes se correlacionan con la expresión de citoquinas proinflamatorias y citoquinas piroptóticas, la liberación de factores de adhesión endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones clínicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes críticamente enfermos no sépticos, sépticos y de shock séptico. Nuestro enfoque ayudará a caracterizar rápidamente las respuestas inmunes alteradas en pacientes sépticos y de shock séptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilación del ADN en el control del sistema inmune séptico. Nuestros resultados demostraron el papel central de la metilación del ADN modulando la respuesta molecular en los pacientes de shock séptico y contribuyendo a la inmunosupresión, a través de la alteración de los patrones de metilación de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1β and IL-1α. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    Reforming the United Nations

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    The thesis deals with the financial crisis that the United Nations faced starting in 1985 when the US Congress decided to withhold a significant part of the US contribution to the UN regular budget in order to force a greater say for the major contributors on budgetary issues, budgetary restraint and greater efficiency. The UN responded by the adoption of resolution 41/213 of 19 December 1986 that was based on the recommendations of a Group of High-level Intergovernmental Experts ("G-18") set up a year earlier. A new system was introduced regarding the formulation of the regular budget of the United Nations Organisation and a broader process of reform was initiated including a restructuring of the Secretariat and of the intergovernmental machinery in the economic and social fields. After an introductory chapter (Chapter I), the thesis examines the UN problems at the budgetary/financial and administrative/structural levels, the solutions proposed from within and without the United Nations established framework and the actual attempts at reform (Chapters II and ifi). The realisation that the implementation of reforms is rather disjointed and often unsuccessful (e.g. the failure to restructure the intergovernmental machi.neiy) prompts a search for the deeper causes of the UN problems at the political level and the attitudes of the main actors, namely the USA, the USSR, some up-and-coming states, notably Japan, the Third World states and, finally, of the UN Secretary-General and the Secretariat (Chapter 1V). Although the financial crisis may have subsided since 1988 and the USA seem committed to paying up their dues, the deeper UN crisis of identity has not been resolved and is expected to resurface if no bold steps are taken. In that direction, some possible alternative courses for the UN in the future are discussed drawing upon theory and practice (Chapte

    Botanical Journeys and China's Colonial Frontiers: 1840-1940

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    Over recent years, a body of scholarship has emerged on the topic of European and American travel writing in China. This thesis contributes to this growing field by examining four writers who travelled in China and worked as plant collectors and botanists. Largely forgotten today, these writers were influential and successful in their own day. Despite differences in geographical location and historical period, there are a number of common links that make a comparison of these travel writings productive. As travellers seeking botanical rarity and novelty, these writers explored regions of China unknown in the West, which over a period of one hundred years expanded outwards from the fringes of the treaty port areas to more remote regions of China's southwest. These writers, therefore, were on the frontiers of Western knowledge of China, and an examination of their writing provides important insights into the ways in which racial, geographical, and ecological differences were articulated and understood in the context of colonial and scientific exploration. While discussing how such differences have imperial significance, this study will also call attention to the instability of colonialist discourse in the context of China. Rather than focus exclusively on questions of imperialism, this study will show how representations of China's periphery regions also speak to metropolitan literary and cultural concerns, and a close reading of these travel writings shows that China offered powerful imaginary landscapes for home audiences. This project is organised chronologically and the chapters are divided according to the authors, with the exception of the first chapter where I introduce the historical and theoretical framework of the study and the final concluding chapter where I consider the significance of this study in the context of modern China

    In search of 'The people of La Manche': A comparative study of funerary practices in the Transmanche region during the late Neolithic and Early Bronze Age (250BC-1500BC)

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    This research project sets out to discover whether archaeological evidence dating between 2500 BC - 1500 BC from supposed funerary contexts in Kent, flanders and north-eastern Transmanche France is sufficient to make valid comparisons between social and cultural structures on either side of the short-sea Channel region. Evidence from the beginning of the period primarily comes in the form of the widespread Beaker phenomenon. Chapter 5 shows that this class of data is abundant in Kent but quite sparse in the Continental zones - most probably because it has not survived well. This problem also affects the human depositional evidence catalogued in Chapter 6, particularly in Fanders but also in north-eastern Transmanche France. This constricts comparative analysis, however, the abundant data from Kent means that general trends are still discernible. The quality and volume of data relating to the distribution, location, morphology and use of circular monuments in all three zones is far better - as demonstrated in Chapter 7 -mostly due to extensive aerial surveying over several decades. When the datasets are taken as a whole, it becomes possible to successfully apply various forms of comparative analyses. Most remarkably, this has revealed that some monuments apparently have encoded within them a sophisticated and potentially symbolically charged geometric shape. This, along with other less contentious evidence, demonstrates a level of conformity that strongly suggests a stratum of cultural homogeneity existed throughout the Transmanche region during the period 2500 BC - 1500 BC. The fact that such changes as are apparent seem to have developed simultaneously in each of the zones adds additional weight to the theory that contact throughout the Transmanche region was endemic. Even so, it may not have been continuous; there may actually have been times of relative isolation - the data is simply too course to eliminate such a possibility

    Studies on the insecticidal mechanism of Bacillus thuringiensis Vip3A and Cry proteins

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    El control de plagas y patógenos ha tenido un efecto importante en la mejora del rendimiento de los sistemas agrícolas a nivel mundial. Diferentes tipos de insecticidas químicos se han usado extensivamente durante mucho tiempo para el control de plagas de insectos. Debido a la aparición de resistencias, problemas de contaminación de aguas y problemas de salud humana causados por dichos insecticidas de síntesis, la agricultura moderna necesita una estrategia de gestión integrada de plagas más saludable, respetuosa con el medio ambiente y sostenible. El uso de Bacillus thuringiensis (Bt) y sus proteínas insecticidas para el control de plagas es una de las estrategias biotecnológicas más importantes hasta la fecha. Además, los genes que codifican sus proteínas insecticidas han sido transferidos a plantas, las cuales están siendo utilizadas comercialmente, desde 1996 en gran parte del mundo para el control eficiente de numerosas plagas de insectos. En los últimos años, una nueva subclase de proteínas insecticidas secretables (Vip3) producida durante el crecimiento vegetativo de Bt se ha considerado para la aplicación combinada con las convencionalmente empleadas proteínas Cry, cuya aplicación se ve amenazada por la aparición de poblaciones de insectos resistentes. Las proteínas Vip3 no tienen homología de secuencia con las proteínas Cry y son tóxicas para insectos lepidópteros, sin embargo, su modo de acción todavía no se conoce completamente. En este proyecto de tesis, con el objetivo de mejorar su aplicación en el control biotecnológico de plagas y la comprensión del modo de acción de las proteínas Vip3, se estudiaron diversos aspectos de su actividad insecticida (espectro de acción, resistencia cruzada e interacción con otras proteínas), y se realizó un estudio de los residuos clave para el mantenimiento de la estructura tridimensional y la toxicidad de la proteína Vip3Af mediante mutagénesis dirigida. También analizamos la posible implicación de la unión a receptores en la aparición de resistencia utilizando una cepa resistente que había sido seleccionada con Vip3Aa. En primer lugar, se investigó la toxicidad de 10 toxinas Bt (Cry1Ab, Cry1Ac, Cry1Ah, Cry1Fa, Cry2Aa, Cry2b, Cry1Ie, Vip3Aa19, Vip3Aa16 y Vip3Ca) frente a Mythimna separata (plaga agrícola muy destructiva en Asia y Australia), así como su aplicación combinada mediante bioensayos llevados a cabo en laboratorio. Los resultados mostraron que la concentración letal media LC50 (Cry1Ac/Vip3Aa19/Vip3Ca 3061 veces) se obtuvo rápidamente después de 8 o 9 generaciones de selección en laboratorio. Sin embargo, no se obtuvo resistencia notable seleccionando con Cry1Ab o Cry1F en la misma población y durante el mismo número de generaciones. En un estudio realizado por otros investigadores, también se encontró una respuesta rápida similar a la selección de Vip3Aa en H. virescens, alcanzando un nivel de resistencia > 2300 veces mayor en la décima generación. Es importante hacer notar que esta rápida evolución de la selección en condiciones de laboratorio contrasta con los resultados obtenidos con las proteínas Cry1, tanto en nuestro trabajo como por otros autores: una la población de O. furnacalis adquirió un nivel de resistencia a Cry1Ab de alrededor de 100 veces sólo después de 35 generaciones de selección; de manera similar, una población de O. nubilalis desarrolló una resistencia de más de 3000 veces a Cry1F después de 35 generaciones de selección. Esta diferencia en respuesta a la selección, además de reflejar una frecuencia mucho mayor de alelos de resistencia para Vip3Aa, puede sugerir diferencias en los mecanismos de resistencia a las proteínas Vip3Aa y Cry1, lo cual queda en evidencia cuando se estudia la unión de Vip3A a BBMV de insectos resistentes El análisis de la unión de 125I-Vip3Aa a BBMV de larvas de M. separata tanto de insectos susceptibles y resistentes no reveló ninguna diferencia de unión, ya sea cualitativa o cuantitativa. Los resultados sugieren que la unión alterada a los receptores de la membrana del intestino medio no es el principal mecanismo de resistencia a la proteína Vip3Aa. Numerosos estudios han demostrado que la alteración de los receptores de membrana es un mecanismo evolutivo común que confiere altos niveles de resistencia a las proteínas Cry, pero nunca se ha establecido su relación con la resistencia a Vip3A. Las diferencias de unión cualitativas o c
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