24,864 research outputs found

    The place where curses are manufactured : four poets of the Vietnam War

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    The Vietnam War was unique among American wars. To pinpoint its uniqueness, it was necessary to look for a non-American voice that would enable me to articulate its distinctiveness and explore the American character as observed by an Asian. Takeshi Kaiko proved to be most helpful. From his novel, Into a Black Sun, I was able to establish a working pair of 'bookends' from which to approach the poetry of Walter McDonald, Bruce Weigl, Basil T. Paquet and Steve Mason. Chapter One is devoted to those seemingly mismatched 'bookends,' Walt Whitman and General William C. Westmoreland, and their respective anthropocentric and technocentric visions of progress and the peculiarly American concept of the "open road" as they manifest themselves in Vietnam. In Chapter, Two, I analyze the war poems of Walter McDonald. As a pilot, writing primarily about flying, his poetry manifests General Westmoreland's technocentric vision of the 'road' as determined by and manifest through technology. Chapter Three focuses on the poems of Bruce Weigl. The poems analyzed portray the literal and metaphorical descent from the technocentric, 'numbed' distance of aerial warfare to the world of ground warfare, and the initiation of a 'fucking new guy,' who discovers the contours of the self's interior through a set of experiences that lead from from aerial insertion into the jungle to the degradation of burning human feces. Chapter Four, devoted to the thirteen poems of Basil T. Paquet, focuses on the continuation of the descent begun in Chapter Two. In his capacity as a medic, Paquet's entire body of poems details his quotidian tasks which entail tending the maimed, the mortally wounded and the dead. The final chapter deals with Steve Mason's JohnnY's Song, and his depiction of the plight of Vietnam veterans back in "The World" who are still trapped inside the interior landscape of their individual "ghettoes" of the soul created by their war-time experiences

    Western Libraries Inclusive Language Guide

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    Learning from the COVID-19 Pandemic: How Faculty Experiences Can Prepare Us for Future System-Wide Disruption

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    The COVID-19 pandemic provided education researchers with a natural experiment: an opportunity to investigate the impacts of a system-wide, involuntary move to online teaching and to assess the characteristics of individuals who adapted more readily. To capture the impacts in real time, our team recruited college-level geoscience instructors through the National Association of Geoscience Teachers (NAGT) and American Geophysical Union (AGU) communities to participate in our study in the spring of 2020. Each weekday for three successive weeks, participants (n = 262) were asked to rate their experienced disruption in four domains: teaching, research, ability to communicate with their professional community, and work-life balance. The rating system (a scale of 1–5, with 5 as severely disrupted) was designed to assess (a) where support needs were greatest, (b) how those needs evolved over time, and (c) respondents’ capacity to adapt. In addition, participants were asked two open-response questions, designed to provide preliminary insights into how individuals were adapting—what was their most important task that day and what was their greatest insight from the previous day. Participants also provided information on their institution type, position, discipline, gender, race, dependents, and online teaching experience (see supplemental material)

    Nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis

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    Dietary nitrate lowers the oxygen cost of submaximal exercise, but precise mechanistic insight into how this occurs is lacking. Research suggests that dietary nitrate may render oxidative ATP synthesis more efficient, but evidence is inconclusive at present. This thesis aimed to establish how nitrite (a reduced form of nitrate) affects the bioenergetics of cultured skeletal muscle cells. Comparison between the acute effects of nitrite and insulin, a hormonal regulator of muscle function that increases mitochondrial efficiency, was explored to assess possible mechanistic overlap. Calculation of real-time intracellular ATP synthesis rates from simultaneous oxygen consumption and medium acidification measurements revealed the effects of sodium nitrite and insulin on intact rat (L6) myoblasts and myotubes. These extracellular flux data were also used to determine how mitochondrial and glycolytic ATP supply is used to fuel ATP-demanding processes. The data presented in this thesis revealed that both nitrite and insulin acutely stimulate glycolytic ATP synthesis. This stimulation occurs without significant mitochondrial ATP supply changes, thus increasing the glycolytic index of myocytes. Consequently, nitrite and insulin lower the oxygen cost of cellular ATP supply. Notably, insulin lowers oxygen consumption linked to mitochondrial proton leak, thus increasing mitochondrial efficiency. Nitrite does not improve coupling efficiency in myoblasts or myotubes. Further investigations revealed that stimulation of glycolytic ATP supply is not secondary to increased glucose availability. In myotubes, glycolytic stimulation persists in the presence of a mitochondrial uncoupler, suggesting that glycolysis is increased directly. In myoblasts, stimulation is annulled by uncoupler, suggesting that glycolysis increases indirectly, via increased ATP consumption. The molecular targets of nitrite and insulin remain unclear, but the data exclude stimulation of protein synthesis. Together, the data demonstrate that nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis. The data inform the ongoing debate regarding the mechanism by which dietary nitrate lowers the oxygen cost of exercise, suggesting a push toward a more glycolytic phenotype. Such mechanistic insight is crucial for achieving the full translational potential of dietary nitrate

    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

    Clinicians' experiences of using the MCA (2005) with people with intellectual disabilities

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    Section A is a narrative synthesis of the empirical literature of professionals’ knowledge of the MCA and how they apply it when working with people with intellectual disabilities (ID). Eleven papers were identified for inclusion in this review. Four themes, with subthemes, were identified: ‘processes involved’, ‘working with complexity’, ‘knowledge gaps and variability’ and ‘assessor needs’. Methodological strengths and weaknesses are also considered. Findings are discussed in relation to clinical implications and recommendations for future research are outlined. Section B is an empirical study using Interpretative Phenomenological Analysis to explore the experiences of clinicians using the MCA (2005) with people with ID to assess capacity to consent to sex. Eight clinicians, who had completed between 2 and 40-50 (mode=2) MCA assessments regarding consent to sex. Three superordinate themes, with subthemes, are outlined and discussed in relation to the existing literature. Limitations, clinical implications and areas of future research are considered

    Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study

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    From Springer Nature via Jisc Publications RouterHistory: received 2021-11-02, accepted 2022-01-16, registration 2022-01-18, pub-electronic 2022-02-02, online 2022-02-02, collection 2022-12Publication status: PublishedFunder: Albireo Pharma, Inc.Abstract: Background: Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included. Results: The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30–49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient’s PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days). Conclusions: The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances

    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
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