73,661 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

    Structural and Attitudinal Barriers to Bicycle Ownership and Cycle-Based Transport in Gauteng, South Africa

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    Policies that aim to facilitate and promote non-motorised transport (NMT), and in particular cycling, have been developed by many high-income countries facing increasingly congested roads and saturated public transport systems. Such policies are also emerging in many low- and middle-income settings where high rates of urbanisation have led to similar problems with motorised transport. The aim of the present study was to better understand the potential structural and attitudinal barriers to cycle-based transport in one such context: South Africa’s Gauteng Province, the industrial powerhouse of sub-Saharan Africa that has recently made a firm commitment to NMT. The study focussed on demographic and socioeconomic variation in bicycle and car ownership, and related this to: (1) the reported use of motorised and non-motorised transport (both private and public); and (2) perceived ‘problems’ with cycling. The analyses drew on interviews with key respondents from n = 27,490 households conducted in 2013 as part of the third Quality of Life survey undertaken by the Gauteng City Regional Observatory. The survey contained items on three outcomes of interest: household vehicle ownership (bicycles and cars); modes of transport used for the “trips” most often made; and respondents’ “single biggest problem with… cycling”. Respondent- and household-level demographic and socioeconomic determinants of these outcomes were examined using descriptive and multivariable statistical analyses, the latter after adjustment for measured potential confounders identified using a theoretical causal path diagram (in the form of a directed acyclic graph). Of the n = 26,469 households providing complete data on all of the variables examined in the present study, only n = 8722 (32.9%) owned a car and fewer still (n = 2244; 8.4%) owned a bicycle. The ownership of these assets was commonest amongst wealthier, economically active households; and those that owned a car had over five times the odds of also owning a bicycle, even after adjustment for potential confounding (OR 5.17; 95% CI 4.58, 5.85). Moreover, of household respondents who reported making ‘trips’ during the preceding month (n = 18,209), over two-thirds of those whose households owned a car (70.1%) reported private car-based transport for such trips, while only 3.2% of those owning a bicycle reported cycling. Amongst the specific responses given to the item requesting the “single biggest problem with… cycling” by far the commonest was “Don’t know how to cycle” (32.2%), less than half as many citing “Vehicle accident risk” (15.9%), and fewer still: “Destination is too far” (13.9%); “Crime” (10.3%); “Too much effort” (9.2%); or “Lack of good paths” (4.6%). While the first of these reasons was commonest amongst poorer households, concerns about risk and effort were both most common amongst better educated, economically active and wealthier/better serviced households. In contrast, concerns over (cycle) paths were only common amongst those owning bicycles. The low prevalence of household bicycle ownership, and the disproportionate number of households owning bicycles that also owned cars, might explain the very small proportion of the ‘the trips most often made’ that involved cycle-based transport (0.3%), and the preferential use of cars amongst households owning both bicycles and cars. Low levels of bicycle ownership might also explain why so many respondents cited “Don’t know how” as the “single biggest problem with… cycling”; although risk and effort were also substantial concerns (presumably for many who did, and some who did not, know how to cycle); the lack of suitable cycle lanes being only primarily a concern for those who actually owned bicycles. Structural and attitudinal barriers to cycle-based transport limit the use of cycle-based transport in Gauteng, not only amongst the vast majority of household respondents who lack the means to cycle (and the means to learn how), but also amongst those dissuaded from learning to cycle, purchasing a bicycle and/or using a bicycle they own by: the risks and effort involved; the lack of suitable cycle paths; and/or because they also own a car and prefer to drive than cycle

    The JCMT BISTRO Survey: Multi-wavelength polarimetry of bright regions in NGC 2071 in the far-infrared/submillimetre range, with POL-2 and HAWC+

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    Polarized dust emission is a key tracer in the study of interstellar medium and of star formation. The observed polarization, however, is a product of magnetic field structure, dust grain properties and grain alignment efficiency, as well as their variations in the line of sight, making it difficult to interpret polarization unambiguously. The comparison of polarimetry at multiple wavelengths is a possible way of mitigating this problem. We use data from HAWC+/SOFIA and from SCUBA-2/POL-2 (from the BISTRO survey) to analyse the NGC 2071 molecular cloud at 154, 214 and 850 μm. The polarization angle changes significantly with wavelength over part of NGC 2071, suggesting a change in magnetic field morphology on the line of sight as each wavelength best traces different dust populations. Other possible explanations are the existence of more than one polarization mechanism in the cloud or scattering from very large grains. The observed change of polarization fraction with wavelength, and the 214-to-154 μm polarization ratio in particular, are difficult to reproduce with current dust models under the assumption of uniform alignment efficiency. We also show that the standard procedure of using monochromatic intensity as a proxy for column density may produce spurious results at HAWC+ wavelengths. Using both long-wavelength (POL-2, 850 μm) and short-wavelength (HAWC+, ≲200μm) polarimetry is key in obtaining these results. This study clearly shows the importance of multi-wavelength polarimetry at submillimeter bands to understand the dust properties of molecular clouds and the relationship between magnetic field and star formation

    The Time Devil runs amok: How I improved my creative practice by adopting a multimodal approach for a specific audience.

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    This research illustrates how teacher-writers can improve their craft and pedagogy by writing for a specific audience, namely school children. It also illustrates why they might do so. It interrogates what was learnt from an innovative collaboration between a university teacher-education department, an inner-city secondary school and the United Kingdom’s National Maritime Museum (NMM). Multimodality (Barnard 2019) inspired the project: local spaces, institutional settings, historical objects, photographs, pictures, time-travelling films and narratives motivated the teacher-writer and participants to read and respond imaginatively to the world. The author found that the project caused him to “remediate” his own practice: to transfer “existing skills in order to tackle new genres” (Barnard 2019: 121). This process enabled him to become a more effective writer and teacher. The research shows that the problem of multimodal overload – having too much choice regarding what to write about and the many forms writing can take – can be circumnavigated if participants are given both autonomy and constraints. It illustrates in some depth how the concept of reciprocity is vital to adopt if writers are to improve their craft

    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

    Conservation agriculture affects grain and nutrient yields of Maize (Zea Mays L.) and can impact food and nutrition security in Sub-Saharan Africa

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    Maize is a major staple and plays an essential role in food and nutrition security in Sub-Saharan Africa (SSA). Conservation agriculture (CA), a climate-smart agriculture practise based on minimum soil disturbance, crop residue retention, and crop diversification, has been widely advocated but without extensive research on the impact it may have on maize nutrient composition, and food and nutrition security. This study assessed the grain yield, macro- and micronutrient mineral content, and nutrient yield of eight maize varieties grown in Malawi, and how these are affected by CA practises over two seasons. The minerals were analysed by inductively coupled plasma (ICP) coupled to optical emission spectroscopy (OES) and to mass spectroscopy (MS). Grain yield and Se content differed among the varieties, while C, N, Fe, K, Mg, Mn, P, and Zn were similar. The local variety Kanjerenjere showed lowest grain and nutrient yields. The open-pollinated varieties (OPVs) concentrated more minerals than the F1 hybrids, but the latter showed higher yields for both grain and nutrients. Typical consumption of the eight maize varieties could fully meet the protein and Mg dietary reference intake (DRIs) of Malawian children (1–3 years), as well as Mg and Mn needs of adult women (19–50 years), but their contribution to dietary requirements was low for Fe (39–41%) and K (13–21%). The trials showed that CA increased grain yield (1.2- to 1.8-fold) and Se content (1.1- to 1.7-fold), but that it had no effect on C, K, Mg, P, and Zn, and that N (1.1- to 1.2-fold), Mn (1.1- to 1.8-fold), and Fe (1.3- to 3.4-fold) were reduced. The high increase in grain yield under CA treatments resulted in increased yields of protein and Se, no effect on the yields of K, Mg, Mn, P, Zn, and reduced Fe yield. Conservation agriculture could contribute in reducing the risk of Se deficiency in Malawian women and children but exacerbates the risk of Fe deficiency. A combination of strategies will be needed to mitigate some of the foreseen effects of climate change on agriculture, and food and nutrition security, and improve nutrient intake

    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, Carnivàle (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

    Studies of strategic performance management for classical organizations theory & practice

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    Nowadays, the activities of "Performance Management" have spread very broadly in actually every part of business and management. There are numerous practitioners and researchers from very different disciplines, who are involved in exploring the different contents of performance management. In this thesis, some relevant historic developments in performance management are first reviewed. This includes various theories and frameworks of performance management. Then several management science techniques are developed for assessing performance management, including new methods in Data Envelopment Analysis (DEA) and Soft System Methodology (SSM). A theoretical framework for performance management and its practical procedures (five phases) are developed for "classic" organizations using soft system thinking, and the relationship with the existing theories are explored. Eventually these results are applied in three case studies to verify our theoretical development. One of the main contributions of this work is to point out, and to systematically explore the basic idea that the effective forms and structures of performance management for an organization are likely to depend greatly on the organizational configuration, in order to coordinate well with other management activities in the organization, which has seemingly been neglected in the existing literature of performance management research in the sense that there exists little known research that associated particular forms of performance management with the explicit assumptions of organizational configuration. By applying SSM, this thesis logically derives some main functional blocks of performance management in 'classic' organizations and clarifies the relationships between performance management and other management activities. Furthermore, it develops some new tools and procedures, which can hierarchically decompose organizational strategies and produce a practical model of specific implementation steps for "classic" organizations. Our approach integrates popular types of performance management models. Last but not least, this thesis presents findings from three major cases, which are quite different organizations in terms of management styles, ownership, and operating environment, to illustrate the fliexbility of the developed theoretical framework

    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

    Electromethanogenesis at medium-low temperatures: Impact on performance and sources of variability

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    .In this study we aimed to understand the impact of medium–low temperatures on the two main steps that usually comprise the electromethanogenesis (EM) process: electrothrophic hydrogenesis and hydrogenothrophic methanogenesis. Results revealed that pure CO2 could effectively be converted into a high-purity biogas (∼90:10 CH4/CO2) at 30 °C. However, when temperature was reduced to 15 °C, methane richness greatly decreased (∼40:60 CH4/CO2). This deterioration in performance was mostly attributed to a decline in methanogenic activity (represented mainly by Methanobacterium and Methanobrevibacter). In contrast, the hydrogenic activity (mostly Desulfomicrobium) did not suffer any significant decay. Results also seemed to indicate that methanogenesis, rather than hydrogenesis, is the main source of variability in EM. Increasing the temperature again to 30 °C restored previous performance, which highlights the resilience of EM to wide temperature fluctuations (from 30 to 15 and back 30 °C).S
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