40,821 research outputs found

    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

    Interactive Sonic Environments: Sonic artwork via gameplay experience

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    The purpose of this study is to investigate the use of video-game technology in the design and implementation of interactive sonic centric artworks, the purpose of which is to create and contribute to the discourse and understanding of its effectiveness in electro-acoustic composition highlighting the creative process. Key research questions include: How can the language of electro-acoustic music be placed in a new framework derived from videogame aesthetics and technology? What new creative processes need to be considered when using this medium? Moreover, what aspects of 'play' should be considered when designing the systems? The findings of this study assert that composers and sonic art practitioners need little or no coding knowledge to create exciting applications and the myriad of options available to the composer when using video-game technology is limited only by imagination. Through a cyclic process of planning, building, testing and playing these applications the project revealed advantages and unique sonic opportunities in comparison to other sonic art installations. A portfolio of selected original compositions, both fixed and open are presented by the author to complement this study. The commentary serves to place the work in context with other practitioners in the field and to provide compositional approaches that have been taken

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

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    La sepsis es una afecci贸n potencialmente mortal causada por una respuesta anormal del hu茅sped a una infecci贸n, produciendo respuestas fisiol贸gicas alteradas que da帽an los propios tejidos del paciente y pueden provocar disfunci贸n org谩nica e incluso la muerte. Asimismo, algunos pacientes s茅pticos progresan a shock s茅ptico, caracterizado por alteraciones circulatorias, celulares y metab贸licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol贸gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi贸n, la alta complejidad de la fisiopatolog铆a de la sepsis requiere una mayor investigaci贸n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot贸xicos en la sepsis, ya que act煤an como patrones moleculares asociados a da帽o, que inducen estr茅s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci贸n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci贸n mediante la expresi贸n de IL-18, IL-1尾 and IL-1伪. Sin embargo, a pesar de la evidencia de activaci贸n del inflamasoma en las c茅lulas 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 activaci贸n del inflamasoma NLRP3 y la piroptosis en las c茅lulas endoteliales, contribuyendo a la disfunci贸n endotelial y la desregulaci贸n de la respuesta inmune mediada por el endotelio. Asimismo, tambi茅n demostramos c贸mo la acetilaci贸n de histonas disminuye la activaci贸n de la piroptosis. Adem谩s, demostramos que la piroptosis se produce en pacientes con shock s茅ptico y los niveles de histonas circulantes se correlacionan con la expresi贸n de citoquinas proinflamatorias y citoquinas piropt贸ticas, la liberaci贸n de factores de adhesi贸n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl铆nicas. 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 cr铆ticamente enfermos no s茅pticos, s茅pticos y de shock s茅ptico. Nuestro enfoque ayudar谩 a caracterizar r谩pidamente las respuestas inmunes alteradas en pacientes s茅pticos y de shock s茅ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci贸n del ADN en el control del sistema inmune s茅ptico. Nuestros resultados demostraron el papel central de la metilaci贸n del ADN modulando la respuesta molecular en los pacientes de shock s茅ptico y contribuyendo a la inmunosupresi贸n, a trav茅s de la alteraci贸n de los patrones de metilaci贸n 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-1尾 and IL-1伪. 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

    Metodolog铆a de intervenci贸n para trabajar ODS. Educaci贸n a trav茅s de las artes

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    La Agenda 2030 presenta 17 Objetivos de Desarrollo Sostenible (ODS), con sus metas e indicadores universales que los pa铆ses miembros de la ONU emplean para enmarcar sus pol铆ticas. Entre las metas del ODS 4 鈥渆ducaci贸n de calidad鈥 encontramos: 鈥渁segurar que todos los alumnos adquieran los conocimientos te贸ricos y pr谩cticos necesarios para promover el desarrollo sostenible, entre otras cosas mediante la educaci贸n para el desarrollo sostenible y los estilos de vida sostenibles, los derechos humanos, la igualdad de g茅nero, la promoci贸n de una cultura de paz y no violencia, la ciudadan铆a mundial y la valoraci贸n de la diversidad cultural y la contribuci贸n de la cultura al desarrollo sostenible鈥. La educaci贸n, se considera el motor de la Agenda 2030 porque, adem谩s de representar el centro del ODS 4, desempe帽a tambi茅n un papel notable en la implementaci贸n de los dem谩s, mejorando su alcance y efectividad. As铆 pues, entre las disciplinas que sustentan este trabajo se escogi贸 la Educaci贸n para el Desarrollo Sostenible y la Ciudadan铆a Global como marco de acci贸n y punto de partida en la formaci贸n de los ciudadanos de un futuro viable, equitativo y habitable. Se continu贸 investigando las oportunidades del desarrollo de la Competencia Intercultural en las relaciones humanas, aquello que diferencia a unas personas de otras puede aportar al conjunto de la sociedad y c贸mo la educaci贸n permitir铆a su aprovechamiento. Con todo ello, se plante贸 el marco did谩ctico de interacci贸n en el cual se implement贸 la interculturalidad en el ejercicio educativo. Se estudi贸 as铆 el poder de las artes como medio de motivaci贸n e inspiraci贸n a la hora de transmitir de la manera m谩s eficaz posible los valores considerados m谩s arriba. El objetivo del presente estudio se centra en demostrar el potencial de las artes para fomentar las competencias comunicativas, sociales, interculturales, emocionales, de ciudadan铆a y sostenibilidad. Para ello, se ha realizado una investigaci贸n aplicada que deriva en una propuesta concreta de intervenci贸n con un programa educativo destinado a la ense帽anza de lenguas, tanto primera como extranjera, en distintos niveles de la educaci贸n formal en Mali y en Espa帽a, aplicando un m茅todo hol铆stico basado en el paradigma interpretativo. A trav茅s de la pintura, la literatura y el cine, se plantean una serie de actividades ideadas para crear un entorno educativo integrador, favorecer el empoderamiento del alumnado y promover el pensamiento cr铆tico, la empat铆a, la resiliencia, la comunicaci贸n, la cooperaci贸n y la educaci贸n intercultural, como competencias esenciales para la consecuci贸n de los 17 ODS, la construcci贸n de un mundo transcultural sostenible y el desarrollo de una ciudadan铆a global preparada para los retos del siglo XXI. En la metodolog铆a de este proceso educativo innovador, multidisciplinar, flexible y adaptable, se ha empleado un an谩lisis del proceso de investigaci贸n para monitorizarlo adecuadamente (DAFO). Cada una de las propuestas presenta una recogida de datos cualitativos (observaci贸n, r煤bricas) y cuantitativos (encuestas, entrevistas) y se ofrece un an谩lisis de contraste de los resultados finales. Con todo, se espera facilitar la exigente tarea que supone hacer consciente a la sociedad de base (desde la misma infancia; desde los niveles m谩s bajos de la misma y en todos los niveles de la educaci贸n formal) de en qu茅 consisten los ODS y su relevancia para hacer de todas las personas corresponsables directas en su consecuci贸n para garantizar un futuro sostenible para toda la ciudadan铆a global.The 2030 Agenda presents 17 Sustainable Development Goals (SDGs), with their universal targets and indicators that UN member countries use to frame their policies. Among the targets of SDG 4 鈥渜uality education,鈥 we find the one that seeks: 鈥渢o ensure that all students acquire the theoretical and practical knowledge necessary to promote sustainable development, among other things through education for sustainable development and sustainable lifestyles, human rights, gender equality, the promotion of a culture of peace and non-violence, world citizenship and the appreciation of cultural diversity and the contribution of culture to sustainable development鈥. Education is considered the engine of the 2030 Agenda because, in addition to representing the centre of SDG 4, it also plays a notable role in the implementation of the others, improving their scope and effectiveness. Among the disciplines that support this research, Education for Sustainable Development and Global Citizenship sets the framework for action and represents a starting point in the formation of citizens for a viable, equitable and habitable future. Global citizenship implies human relations and those and intrinsically shaped by culture. Intercultural Education and, more specifically, the development of Intercultural Competence needed to be considered. What differentiates some people from others can contribute to society as a whole and education is the means to explore and understand. For the design of a didactic framework of interaction, the power of the arts was studied as a means of motivation and inspiration when transmitting the values considered above in the most effective way possible. The objective of this study focuses on proving the potential of the arts to promote communicative, social, intercultural, emotional, citizenship and sustainability skills. For this, the theoretical research derived in a concrete intervention proposal with an educational program in language teaching, both first and foreign languages, at different levels of formal education in Mali and Spain, applying a holistic method based on the interpretive paradigm. Through painting, literature and cinema, a series of activities were designed to create an inclusive educational environment, favour the empowerment of students and promote critical thinking, empathy, resilience, communication, cooperation and intercultural education, as essential skills for the achievement of the 17 SDGs, the construction of a sustainable transcultural world and the development of global citizenship prepared for the challenges of the 21st century. In the methodology of this innovative, multidisciplinary, flexible and adaptable educational process, an analysis of the research process has been used to adequately monitor it (SWOT). Each of the proposals presents a collection of qualitative data (observation, rubrics) and quantitative data (surveys, interviews) and contrast analysis of the final results is offered. All in all, it is expected to facilitate the demanding task of making basic society aware (from childhood itself, from its lowest levels and at all levels of formal education) of what the SDGs consist of and their relevance to make all people directly co-responsible in its achievement to guarantee a sustainable future for all global citizens

    Rainfall Prediction: A Comparative Analysis of Modern Machine Learning Algorithms for Time-Series Forecasting

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    Rainfall forecasting has gained utmost research relevance in recent times due to its complexities and persistent applications such as flood forecasting and monitoring of pollutant concentration levels, among others. Existing models use complex statistical models that are often too costly, both computationally and budgetary, or are not applied to downstream applications. Therefore, approaches that use Machine Learning algorithms in conjunction with time-series data are being explored as an alternative to overcome these drawbacks. To this end, this study presents a comparative analysis using simplified rainfall estimation models based on conventional Machine Learning algorithms and Deep Learning architectures that are efficient for these downstream applications. Models based on LSTM, Stacked-LSTM, Bidirectional-LSTM Networks, XGBoost, and an ensemble of Gradient Boosting Regressor, Linear Support Vector Regression, and an Extra-trees Regressor were compared in the task of forecasting hourly rainfall volumes using time-series data. Climate data from 2000 to 2020 from five major cities in the United Kingdom were used. The evaluation metrics of Loss, Root Mean Squared Error, Mean Absolute Error, and Root Mean Squared Logarithmic Error were used to evaluate the models' performance. Results show that a Bidirectional-LSTM Network can be used as a rainfall forecast model with comparable performance to Stacked-LSTM Networks. Among all the models tested, the Stacked-LSTM Network with two hidden layers and the Bidirectional-LSTM Network performed best. This suggests that models based on LSTM-Networks with fewer hidden layers perform better for this approach; denoting its ability to be applied as an approach for budget-wise rainfall forecast applications

    Dynamic and Static Cognitive Deficits in Schizophrenia and Bipolar Disorder After the First Episode

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    Abstract Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission. A cognitive battery was administered at baseline and follow-up. By combining longitudinal and cross-sectional data, we were able to examine the cognitive profile of patients and controls throughout the entire age range of our sample (16鈥65). Schizophrenia patients exhibited widespread declines in IQ, executive function, visual memory, language ability, and verbal knowledge. However, the ages at which these declines occurred differed between functions. Deficits in verbal memory, working memory, processing speed, and visuospatial ability, on the other hand, were present at the first episode, and remained relatively static thereafter. Bipolar I patients also showed declines in IQ, verbal knowledge, and language ability, albeit at different ages to schizophrenia patients and only in verbal functions. Deficits on measures of verbal memory, processing speed, and executive function remained relatively static. Thus, both schizophrenia and bipolar I patients experienced cognitive decline in general and specific functions after the first episode, but the age at which these declines occurred differed between disorder and function. Cognitive remediation efforts may be most fruitful when targeting individual functions during specific time periods throughout adulthood

    The applied psychology of addictive orientations : studies in a 12-step treatment context.

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    The clinical data for the studies was collected at The PROMIS Recovery Centre, a Minnesota Model treatmentc entre for addictions,w hich encouragesth e membership and use of the 12 step Anonymous Fellowships, and is abstinence based. The area of addiction is contextualised in a review chapter which focuses on research relating to the phenomenon of cross addiction. A study examining the concept of "addictive orientations" in male and female addicts is described, which develops a study conductedb y StephensonM, aggi, Lefever, & Morojele (1995). This presents study found a four factor solution which appeared to be subdivisions of the previously found Hedonism and Nurturance factors. Self orientated nurturance (both food dimensions, shopping and caffeine), Other orientated nurturance (both compulsive helping dimensions and work), Sensation seeking hedonism (Drugs, prescription drugs, nicotine and marginally alcohol), and Power related hedonism (Both relationship dimensions, sex and gambling. This concept of "addictive orientations" is further explored in a non-clinical population, where again a four factor solution was found, very similar to that in the clinical population. This was thought to indicate that in terms of addictive orientation a pattern already exists in this non-clinical population and that consideration should be given to why this is the case. These orientations are examined in terms of gender differences. It is suggested that the differences between genders reflect power-related role relationships between the sexes. In order to further elaborate the significance and meaning behind these orientations, the next two chapters look at the contribution of personality variables and how addictive orientations relate to psychiatric symptomatology. Personality variables were differentially, and to a considerable extent predictably involved with the four factors for both males and females.Conscientiousness as positively associated with "Other orientated Nurturance" and negatively associated with "Sensation seeking hedonism" (particularly for men). Neuroticism had a particularly strong association with the "Self orientated Nurturance" factor in the female population. More than twice the symptomatology variance was explained by the factor scores for females than it was for males. The most important factorial predictors for psychiatric symptomatology were the "Power related hedonism" factor for males, and "Self oriented nurturance" for females. The results are discussed from theoretical and treatment perspectives

    The company she keeps : The social and interpersonal construction of girls same sex friendships

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    This thesis begins a critical analysis of girls' 'private' interpersonal and social relations as they are enacted within two school settings. It is the study of these marginal subordinated worlds productivity of forms of femininity which provides the main narrative of this project. I seek to understand these processes of (best) friendship construction through a feminist multi-disciplinary frame, drawing upon cultural studies, psychoanalysis and accounts of gender politics. I argue that the investments girls bring to their homosocial alliances and boundary drawing narry a psychological compulsion which is complexly connected to their own experiences within the mother/daughter bond as well as reflecting positively an immense social debt to the permissions girls have to be nurturant and ; negatively their own reproduction of oppressive exclusionary practices. Best friendship in particular gives girls therefore, the experience of 'monogamy' continuous of maternal/daughter identification, reminiscent of their positioning inside monopolistic forms of heterosexuality. But these subcultures also represent a subversive discontinuity to the public dominance of boys/teachers/adults in schools and to the ideologies and practices of heterosociality and heterosexuality. By taking seriously their transmission of the values of friendship in their chosen form of notes and diaries for example, I was able to access the means whereby they were able to resist their surveillance and control by those in power over them. I conclude by arguing that it is through a recognition of the valency of these indivisiblly positive and negative aspects to girls cultures that Equal Opportunities practitioners must begin if they are serious about their ambitions. Methods have to be made which enable girls to transfer their 'private' solidarities into the 'public' realm, which unquestionably demands contesting with them the causes and consequences of their implication in the divisions which also contaminate their lives and weaken them

    Strung pieces: on the aesthetics of television fiction series

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    As layered and long works, television fiction series have aesthetic properties that are built over time, bit by bit. This thesis develops a group of concepts that enable the study of these properties, It argues that a series is made of strung pieces, a system of related elements. The text begins by considering this sequential form within the fields of film and television. This opening chapter defines the object and methodology of research, arguing for a non-essentialist distinction between cinema and television and against the adequacy of textual and contextual analyses as approaches to the aesthetics of these shows. It proposes instead that these programmes should be described as televisual works that can be scrutinised through aesthetic analysis. The next chapters propose a sequence of interrelated concepts. The second chapter contends that series are composed of building blocks that can be either units into which series are divided or motifs that unify series and are dispersed across their pans. These blocks are patterned according to four kinds of relations or principles of composition. Repetition and variation are treated in tandem in the third chapter because of their close connection, given that variation emerges from established repetition. Exception and progression are also discussed together in the fourth chapter since they both require a long view of these serial works. The former, in order to be recognised as a deviation from the patterns of repetition and variation. The latter, In order to be understood in Its many dimensions as the series advances. Each of these concepts is further detailed with additional distinctions between types of units, motifs, repetitions, variations, and exceptions, using illustrative examples from numerous shows. In contrast, the section on progression uses a single series as case study, Carniv脿le (2003-05), because this is the overarching principle that encompasses all the others. The conclusion considers the findings of the research and suggests avenues for their application
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