15,397 research outputs found

    Consent and the Construction of the Volunteer: Institutional Settings of Experimental Research on Human Beings in Britain during the Cold War

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    This study challenges the primacy of consent in the history of human experimentation and argues that privileging the cultural frameworks adds nuance to our understanding of the construction of the volunteer in the period 1945 to 1970. Historians and bio-ethicists have argued that medical ethics codes have marked out the parameters of using people as subjects in medical scientific research and that the consent of the subjects was fundamental to their status as volunteers. However, the temporality of the creation of medical ethics codes means that they need to be understood within their historical context. That medical ethics codes arose from a specific historical context rather than a concerted and conscious determination to safeguard the well-being of subjects needs to be acknowledged. The British context of human experimentation is under-researched and there has been even less focus on the cultural frameworks within which experiments took place. This study demonstrates, through a close analysis of the Medical Research Council's Common Cold Research Unit (CCRU) and the government's military research facility, the Chemical Defence Experimental Establishment, Porton Down (Porton), that the `volunteer' in human experiments was a subjective entity whose identity was specific to the institution which recruited and made use of the subject. By examining representations of volunteers in the British press, the rhetoric of the government's collectivist agenda becomes evident and this fed into the institutional construction of the volunteer at the CCRU. In contrast, discussions between Porton scientists, staff members, and government officials demonstrate that the use of military personnel in secret chemical warfare experiments was far more complex. Conflicting interests of the military, the government and the scientific imperative affected how the military volunteer was perceived

    Before the Creation of Time in Plato’s Timaeus

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    I defend, against its more recent critics, a literal, factual, and consistent interpretation of Timaeus’ creation of the cosmos and time. My main purpose is to clarify the assumptions under which a literal interpretation of Timaeus’ cosmology becomes philosophically attractive. I propose five exegetical principles that guide my interpretation. Unlike previous literalists, I argue that assuming a “pre-cosmic time” is a mistake. Instead, I challenge the exegetical assumptions scholars impose on the text and argue that for Timaeus, a mere succession of events and the relations derived from it (before, after, simultaneous with) imply no time, given the narrow definition of the term used in the dialogue. For Timaeus, I explain, time is measurable, regular, and dependent on the motion of the celestial bodies. A mere succession of events like the one needed to understand the creation story and the pre-cosmos requires none of these elements. Readers of Plato erroneously assume that a succession of events implies time, but that is to impose a conception of time absent in the text. The chapter offers a detailed reconstruction of the pre-cosmic stage under a literalist interpretation and argues how it is compatible with the immutable relationship between the Demiurge and the cosmos. This is an open access chapter distributed under the terms of the CC BY-NC 4.0 license. chapter

    Strategies for Early Learners

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    Welcome to learning about how to effectively plan curriculum for young children. This textbook will address: ‱ Developing curriculum through the planning cycle ‱ Theories that inform what we know about how children learn and the best ways for teachers to support learning ‱ The three components of developmentally appropriate practice ‱ Importance and value of play and intentional teaching ‱ Different models of curriculum ‱ Process of lesson planning (documenting planned experiences for children) ‱ Physical, temporal, and social environments that set the stage for children’s learning ‱ Appropriate guidance techniques to support children’s behaviors as the self-regulation abilities mature. ‱ Planning for preschool-aged children in specific domains including o Physical development o Language and literacy o Math o Science o Creative (the visual and performing arts) o Diversity (social science and history) o Health and safety ‱ Making children’s learning visible through documentation and assessmenthttps://scholar.utc.edu/open-textbooks/1001/thumbnail.jp

    Building body identities - exploring the world of female bodybuilders

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    This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances

    Image classification over unknown and anomalous domains

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    A longstanding goal in computer vision research is to develop methods that are simultaneously applicable to a broad range of prediction problems. In contrast to this, models often perform best when they are specialized to some task or data type. This thesis investigates the challenges of learning models that generalize well over multiple unknown or anomalous modes and domains in data, and presents new solutions for learning robustly in this setting. Initial investigations focus on normalization for distributions that contain multiple sources (e.g. images in different styles like cartoons or photos). Experiments demonstrate the extent to which existing modules, batch normalization in particular, struggle with such heterogeneous data, and a new solution is proposed that can better handle data from multiple visual modes, using differing sample statistics for each. While ideas to counter the overspecialization of models have been formulated in sub-disciplines of transfer learning, e.g. multi-domain and multi-task learning, these usually rely on the existence of meta information, such as task or domain labels. Relaxing this assumption gives rise to a new transfer learning setting, called latent domain learning in this thesis, in which training and inference are carried out over data from multiple visual domains, without domain-level annotations. Customized solutions are required for this, as the performance of standard models degrades: a new data augmentation technique that interpolates between latent domains in an unsupervised way is presented, alongside a dedicated module that sparsely accounts for hidden domains in data, without requiring domain labels to do so. In addition, the thesis studies the problem of classifying previously unseen or anomalous modes in data, a fundamental problem in one-class learning, and anomaly detection in particular. While recent ideas have been focused on developing self-supervised solutions for the one-class setting, in this thesis new methods based on transfer learning are formulated. Extensive experimental evidence demonstrates that a transfer-based perspective benefits new problems that have recently been proposed in anomaly detection literature, in particular challenging semantic detection tasks

    RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s disease targeting RNA/HuR complexes

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    MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy. HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinson’s disease (PD). PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies. In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD. To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells. To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3’ untranslated region (3’-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression. In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies

    TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH

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    Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on people’s lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)

    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
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